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Panula P. Histamine receptors, agonists, and antagonists in health and disease. HANDBOOK OF CLINICAL NEUROLOGY 2021; 180:377-387. [PMID: 34225942 DOI: 10.1016/b978-0-12-820107-7.00023-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Histamine in the brain is produced by a group of tuberomamillary neurons in the posterior hypothalamus and a limited number of mast cells in different parts of the brain. Four G-protein-coupled receptors mediate the effects of histamine. Two of these receptors, H3 and H4 receptors, are high-affinity receptors in the brain and immune system, respectively. The two classic histamine receptors, H1 receptor and H2 receptor, are well known as drug targets for allergy and gastric ulcer, respectively. These receptors have lower affinity for histamine than the more recently discovered H3 and H4 receptors. The H1 and H2 receptors are important postsynaptic receptors in the brain, and they mediate many of the central effects of histamine on, e.g., alertness and wakefulness. H3 receptor is a pre- and postsynaptic receptor, which regulates release of histamine and several other neurotransmitters, including serotonin, GABA, and glutamate. H4 receptor is found in cerebral blood vessels and microglia, but its expression in neurons is not yet well established. Pitolisant, a H3 receptor antagonist, is used to treat narcolepsy and hypersomnia. H1 receptor antagonists have been used to treat insomnia, but its use requires precautions due to potential side effects. H2 receptor antagonists have shown efficacy in treatment of schizophrenia, but they are not in widespread clinical use. H4 receptor ligands may in the future be tested for neuroimmunological disorders and potentially neurodegenerative disorders in which inflammation plays a role, but clinical tests have not yet been initiated.
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Affiliation(s)
- Pertti Panula
- Department of Anatomy, University of Helsinki, Helsinki, Finland.
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McClain JL, Mazzotta EA, Maradiaga N, Duque-Wilckens N, Grants I, Robison AJ, Christofi FL, Moeser AJ, Gulbransen BD. Histamine-dependent interactions between mast cells, glia, and neurons are altered following early-life adversity in mice and humans. Am J Physiol Gastrointest Liver Physiol 2020; 319:G655-G668. [PMID: 32996781 PMCID: PMC7792668 DOI: 10.1152/ajpgi.00041.2020] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Early-life adversity contributes to the development of functional bowel disorders later in life through unresolved mechanisms. Here, we tested the hypothesis that early-life adversity alters anatomical and functional interactions between mast cells and enteric glia. The effects of early-life stress were studied using the neonatal maternal separation (NMS) stress mouse model. Anatomical relationships between mast cells and enteric glia were assessed using immunohistochemistry and mast cell reporter mice (Mcpt5Cre;GCaMP5g-tdT). Immunohistochemistry was used to assess the expression of histamine, histamine 1 (H1) receptors, and glial fibrillary acidic protein. Functional responses of glia to mast cell mediators were assessed in calcium imaging experiments using Sox10CreERT2;GCaMP5g-tdT mice and cultured human enteric glial cells. NMS increases mast cell numbers at the level of the myenteric plexus and their proximity to myenteric ganglia. Myenteric glia respond to mediators released by activated mast cells that are blocked by H1 receptor antagonists in mice and humans and by blocking neuronal activity with tetrodotoxin in mouse tissue. Histamine replicates the effects of mast cell supernatants on enteric glia, and NMS increases histamine production by mast cells. NMS reduces glial responses to mast cell mediators in mouse tissue, while potentiating responses in cultured human enteric glia. NMS increases myenteric glial fibrillary acidic protein expression and reduces glial process length but does not cause neurodegeneration. Histamine receptor expression is not altered by NMS and is localized to neurons in mice, but glia in humans. Early-life stress increases the potential for interactions between enteric glia and mast cells, and histamine is a potential mediator of mast cell-glial interactions through H1 receptors. We propose that glial-mast cell signaling is a mechanism that contributes to enteric neuroplasticity driven by early-life adversity.NEW & NOTEWORTHY Early-life adversity places an individual at risk for developing functional gastrointestinal disorders later in life through unknown mechanisms. Here, we show that interactions between mast cells and glia are disrupted by early-life stress in mice and that histamine is a potential mediator of mast cell-glial interactions.
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Affiliation(s)
- Jonathon L. McClain
- 1Department of Physiology, Michigan State University, East Lansing, Michigan
| | - Elvio A. Mazzotta
- 2Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Nidia Maradiaga
- 3Gastrointestinal Stress Biology Laboratory, Department Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan
| | - Natalia Duque-Wilckens
- 1Department of Physiology, Michigan State University, East Lansing, Michigan,3Gastrointestinal Stress Biology Laboratory, Department Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan
| | - Iveta Grants
- 2Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Alfred J. Robison
- 1Department of Physiology, Michigan State University, East Lansing, Michigan
| | - Fievos L. Christofi
- 2Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Adam J. Moeser
- 1Department of Physiology, Michigan State University, East Lansing, Michigan,3Gastrointestinal Stress Biology Laboratory, Department Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan
| | - Brian D. Gulbransen
- 1Department of Physiology, Michigan State University, East Lansing, Michigan
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3
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Muindi F, Colas D, Ikeme J, Ruby NF, Heller HC. Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice. PLoS One 2015; 10:e0128175. [PMID: 26083020 PMCID: PMC4471207 DOI: 10.1371/journal.pone.0128175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 04/24/2015] [Indexed: 12/17/2022] Open
Abstract
Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour) induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period.
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Affiliation(s)
- Fanuel Muindi
- Department of Biology, Stanford University, Stanford, California, United States of America
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- * E-mail:
| | - Damien Colas
- Department of Biology, Stanford University, Stanford, California, United States of America
| | - Jesse Ikeme
- Department of Biology, Stanford University, Stanford, California, United States of America
| | - Norman F. Ruby
- Department of Biology, Stanford University, Stanford, California, United States of America
| | - H. Craig Heller
- Department of Biology, Stanford University, Stanford, California, United States of America
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Mast Cell Serotonin Immunoregulatory Effects Impacting on Neuronal Function: Implications for Neurodegenerative and Psychiatric Disorders. Neurotox Res 2015; 28:147-53. [PMID: 26038194 DOI: 10.1007/s12640-015-9533-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 05/15/2015] [Accepted: 05/15/2015] [Indexed: 01/05/2023]
Abstract
Mast cells (MCs) are derived from hemopoietic precursor cells, undergo their maturation in peripheral tissues, and play a significant role in both the innate and adaptive immune response. Cross-linking of the FcεRI on MCs initiates activation of several cytoplasmic protein tyrosine kinases which rapidly lead to phosphorylation and recruitment of adaptor molecules. These effects trigger the release of preformed mediators stored in the cytoplasmic granules, including histamine, serotonin and tryptase, as well as newly synthesized mediators, such as cytokines/chemokines, prostaglandins, leukotrienes, and growth factors. Serotonin (5-HT) is a bioactive monoamine, which has seven specific cell surface membrane bound receptors which are coupled to G-proteins, plays an important role in the central and peripheral nervous system, and is one of the key mediators in signaling between nervous and immune systems. Serotonin is not stored in all MC types but is implicated in MC adhesion, chemotaxis, tumorigenesis, and tissue regeneration through smooth muscle differentiation of stromal cells. Recent evidence indicates that serotonin has immunoregulatory actions that may be important in neuropsychiatric conditions. Chemokines, RANTES/CCL5, MCP-1/CCL2, and related molecules, constitute the C-C class of chemokine supergene family, play a role in regulating T helper-cell cytokine production and MC trafficking, and are involved in histamine and serotonin generation and MC functions. Pro-inflammatory cytokines such as interleukin-1-β and tumor necrosis factor which mediate MC response, are capable of activating p38 MAPK, and might increase serotonin generation through p38 MAPK activation. Here, we review the relationship between MCs and serotonin and its role in inflammatory diseases and neuroimmune interactions.
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Nyengaard JR, Alwasel SH. Practical stereology of the stomach and intestine. Ann Anat 2013; 196:41-7. [PMID: 24365710 DOI: 10.1016/j.aanat.2013.10.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 10/21/2013] [Accepted: 10/22/2013] [Indexed: 02/04/2023]
Abstract
We provide a practical review of the opportunities made available by design-unbiased stereology to estimate cell number, total volume, mean volume and mean height in the rat stomach using enterochromaffin-like cells as an example. The second example comprises estimation of the surface area of well-defined segments of rat colon and the volumes of different layers following surgery and/or treatment which may result in the atrophy or growth of the colon. The pros and cons of the stereologic designs are discussed and the pitfalls and some solutions to these are elucidated.
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Affiliation(s)
- Jens R Nyengaard
- Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Department of Clinical Medicine, Aarhus University, Denmark.
| | - Saleh H Alwasel
- Fetal Programming of Disease' Research Chair, Zoology Department, College of Science, King Saud University, Saudi Arabia
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Wood JD. Nonruminant Nutrition Symposium: Neurogastroenterology and food allergies. J Anim Sci 2011; 90:1213-23. [PMID: 22100595 DOI: 10.2527/jas.2011-4787] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Neurogastroenterology is a subspecialty encompassing relations of the nervous system to the gastrointestinal tract. The central concept is emergence of whole organ behavior from coordinated activity of the musculature, mucosal epithelium, and blood vasculature. Behavior of each effector is determined by the enteric nervous system (ENS). The ENS is a minibrain positioned close to the effectors it controls. The ENS neurophysiology is in the framework of neurogastroenterology. The digestive tract is recognized as the largest lymphoid organ in the body with a unique complement of mast cells. In its position at the "dirtiest" of interfaces between the body and outside world, the mucosal immune system encounters food antigens, bacteria, parasites, viruses, and toxins. Epithelial barriers are insufficient to exclude fully the antigenic load, thereby allowing chronic challenges to the immune system. Observations in antigen-sensitized animals document direct communication between the mucosal immune system and ENS. Communication is functional and results in adaptive responses to circumstances within the lumen that are threatening to the functional integrity of the whole animal. Communication is paracrine and incorporates specialized sensing functions of mast cells for specific antigens together with the capacity of the ENS for intelligent interpretation of the signals. Immuno-neural integration progresses sequentially, beginning with immune detection, followed by signal transfer to the ENS, followed by neural interpretation and then selection of a neural program with coordinated mucosal secretion and a propulsive motor event that quickly clears the threat from the intestinal lumen. Operation of the defense program evokes symptoms of cramping abdominal pain, fecal urgency, and acute watery diarrhea. Investigative approaches to immuno-ENS interactions merge the disciplines of mucosal immunology and ENS neurophysiology into the realm of neurogastroenterology.
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Affiliation(s)
- J D Wood
- Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus 43210, USA.
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Abstract
Histamine is a transmitter in the nervous system and a signaling molecule in the gut, the skin, and the immune system. Histaminergic neurons in mammalian brain are located exclusively in the tuberomamillary nucleus of the posterior hypothalamus and send their axons all over the central nervous system. Active solely during waking, they maintain wakefulness and attention. Three of the four known histamine receptors and binding to glutamate NMDA receptors serve multiple functions in the brain, particularly control of excitability and plasticity. H1 and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as inhibitory auto- and heteroreceptors. Mutual interactions with other transmitter systems form a network that links basic homeostatic and higher brain functions, including sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease.
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Affiliation(s)
- Helmut L Haas
- Institute of Neurophysiology, Heinrich-Heine-University, Duesseldorf, Germany.
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He G, Hu J, Ma X, Li M, Wang H, Meng J, Jia M, Luo X. Sympathetic histamine exerts different pre- and post-synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens. J Neurochem 2008; 106:1710-9. [DOI: 10.1111/j.1471-4159.2008.05532.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Hu J, Chen T, Li M, He G, Meng J, Ma X, Wu Y, Jia M, Luo X. Wide distribution and subcellular localization of histamine in sympathetic nervous systems of different species. Neurosci Res 2007; 59:231-6. [PMID: 17723248 DOI: 10.1016/j.neures.2007.06.1481] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2007] [Revised: 06/25/2007] [Accepted: 06/29/2007] [Indexed: 12/28/2022]
Abstract
Previous studies have demonstrated that histamine (HA) acts as a neurotransmitter in the cardiac sympathetic nervous system of the guinea pig. The aim of the current study was to examine whether HA widely exists in the sympathetic nervous systems of other species and the subcellular localization of HA in sympathetic terminals. An immunofluorescence histochemical multiple-staining technique and anterograde tracing method were employed to visualize the colocalization of HA and norepinephrine (NE) in sympathetic ganglion and nerve fibers in different species. Pre-embedding immunoelectron microscopy was used to observe the subcellular distribution of HA in sympathetic nerve terminals. Under the confocal microscope, coexistence of NE and HA was displayed in the superior cervical ganglion and celiac ganglion neurons of the mouse and dog as well as in the vas deferens, mesenteric artery axon, and varicosities of the mouse and guinea pig. Furthermore, colocalization of NE and HA in cardiac sympathetic axons and varicosities was labeled by biotinylated dextranamine injected into the superior cervical ganglion of the guinea pig. By electron microscopy, HA-like high-density immunoreactive products were seen in the small vesicles of the guinea pig vas deferens. These results provide direct cellular and subcellular morphological evidence for the colocalization of HA and NE in sympathetic ganglion and nerve fibers, and support that HA is classified as a neurotransmitter in sympathetic neurons.
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Affiliation(s)
- Jing Hu
- Department of Pharmacology, The Fourth Military Medical University, Xi'an 710032, PR China
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Li M, Hu J, Chen T, Meng J, Ma X, Li J, Jia M, Luo X. Histamine in Macaca mulatto monkey cardiac sympathetic nerve system: a morphological and functional assessment. Auton Neurosci 2007; 137:37-43. [PMID: 17689150 DOI: 10.1016/j.autneu.2007.06.285] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2007] [Revised: 06/21/2007] [Accepted: 06/28/2007] [Indexed: 11/27/2022]
Abstract
Our previous study demonstrated the co-localization of histamine with norepinephrine (NE) within superior cervical ganglia (SCG), and the release of histamine from sympathetic nerve endings of guinea pig evoked by stimulations. We have now further investigated that whether the histamine can be synthesized, stored and released from the sympathetic nerve systems of Macaca mulatto monkey, and investigated the modulation of the sympathetic endogenous histamine release through histamine H(3) receptor in the monkey cardiac sympathetic nerve system. Double-labeled immunofluorescence technique was applied to investigate co-localization of histamine and NE in SCG of Macaca mulatto monkey. The cardiac sympathetic nerve terminals (synaptosomes) of Macaca mulatto monkey was prepared and depolarized with 50 mmol/L K(+). Histamine released from synaptosomes was detected by spectrofluorometer and regulations of histamine release through Ca(2+), Ca(2+)-channel blockers, H(3)-receptor agonist (R)-alpha-methylhistamine and histamine H(3)-receptor antagonist, thioperamide were observed. Co-localization of histamine and NE was identified within the same neuron of SCG. Release of histamine was Ca(2+)-dependent and inhibited by N-type Ca(2+)-channel blocker omega-conotoxin, but not affected by the L-type Ca(2+)-channel blocker lacidipine. Compound 48/80, a mast cell releaser, did not affect cardiac synaptosome histamine exocytosis. Cardiac synaptosome histamine release was augmented by the enhanced synthesis of histamine or the inhibition of histamine metabolism. Histamine H(3)-receptor activation by (R)-alpha-methylhistamine inhibited high K(+)-evoked histamine release and thioperamide blocked the effects of (R)-alpha-methylhistamine. These results firstly showed that histamine co-existed with NE within sympathetic neurons of monkey and the exocytosis of histamine from sympathetic terminals could be regulated by presynaptic histamine H(3) receptors. Sympathetic histamine may act as a neurotransmitter to modulate sympathetic neurotransmission.
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Affiliation(s)
- Mingkai Li
- Department of Pharmacology, The Fourth Military Medical University, Xi' an 710032, PR China
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11
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Wood JD. Effects of bacteria on the enteric nervous system: implications for the irritable bowel syndrome. J Clin Gastroenterol 2007; 41 Suppl 1:S7-19. [PMID: 17438418 DOI: 10.1097/mcg.0b013e31802f1331] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
A unified scenario emerges when it is considered that a major impact of stress on the intestinal tract is reflected by symptoms reminiscent of the diarrhea-predominant form of irritable bowel syndrome. Cramping abdominal pain, fecal urgency, and explosive watery diarrhea are hallmarks not only of diarrhea-predominant irritable bowel syndrome, but also of infectious enteritis, radiation-induced enteritis, and food allergy. The scenario starts with stress-induced compromise of the intestinal mucosal barrier and continues with microorganisms or other sensitizing agents crossing the barrier and being intercepted by enteric mast cells. Mast cells signal the presence of the agent to the enteric nervous system (ie, the brain-in-the-gut), which uses one of the specialized programs from its library of programs to remove the "threat." This is accomplished by stimulating mucosal secretion, which flushes the threatening agent into the lumen and maintains it in suspension. The secretory response then becomes linked to powerful propulsive motility, which propels the secretions together with the offending agent rapidly in the anal direction. Cramping abdominal pain accompanies the strong propulsive contractions. Urgency is experienced when arrival of the large bolus of liquid distends the recto-sigmoid region and reflexly opens the internal anal sphincter, with continence protection now provided only by central reflexes that contract the puborectalis and external anal sphincter muscles. Sensory information arriving in the brain from receptors in the rapidly distending recto-sigmoid accounts for the conscious sensation of urgency and might exacerbate the individual's emotional stress. The symptom of explosive watery diarrhea becomes self-explanatory in this scenario.
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Affiliation(s)
- Jackie D Wood
- Department of Physiology and Cell Biology, The Ohio State University College of Medicine and Public Health, 1645 Neil Avenue, Columbus, OH 43210, USA.
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12
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Abstract
The investigative evidence and emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many of the functional gastrointestinal disorders. Neurogastroenterological research aims for improved understanding of the physiology and pathophysiology of the digestive subsystems from which the arrays of functional symptoms emerge. The key subsystems for defecation-related symptoms and visceral hyper-sensitivity are the intestinal secretory glands, the musculature and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts for the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication and the brain-gut axis.
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Li M, Hu J, Chen Z, Meng J, Wang H, Ma X, Luo X. Evidence for histamine as a neurotransmitter in the cardiac sympathetic nervous system. Am J Physiol Heart Circ Physiol 2006; 291:H45-51. [PMID: 16399866 DOI: 10.1152/ajpheart.00939.2005] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The colocalization of histamine (HA) and norepinephrine (NE) immunoreactivities was identified within the superior cervical ganglia neurons of the guinea pig. HA and NE immunoreactivity levels were significantly attenuated after chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Coexistence of NE and HA was also visualized in the cardiac sympathetic axon and varicosities labeled with anterograde tracer biotinylated dextran amine. Depolarization of cardiac sympathetic nerve endings (synaptosomes) with 50 mM potassium stimulated endogenous HA release, which was significantly attenuated by 6-OHDA or a vesicular monoamine transporter 2 (VMAT2) inhibitor reserpine pretreatments. Compound 48/80, a mast cell releaser, did not affect cardiac synaptosome HA exocytosis. Furthermore, K+-evoked HA release was abolished by the N-type Ca2+-channel blocker ω-conotoxin but was not affected by the L-type Ca2+-channel blocker lacidipine. Cardiac synaptosome HA exocytosis was augmented by the enhanced synthesis of HA or the inhibition of HA metabolism. HA H3-receptor activation by ( R)-α-methylhistamine inhibited high K+-evoked histamine release. The HA H3receptor antagonist thioperamide enhanced K+-evoked HA release and blocked the ( R)-α-methylhistamine effect. The K+-evoked endogenous NE release was attenuated by preloading the cardiac synaptosomes with l-histidine or quinacrine. These inhibitory effects were reversed by thioperamide or antagonized by α-fluoromethylhistidine. Our findings indicate that high K+-evoked corelease of NE and HA may be inhibited by endogenous HA via activation of presynaptic HA H3-receptors. The H3-receptor may function as an autoreceptor, rather than a heteroreceptor, in the regulation of sympathetic neurotransmission and HA may be a novel sympathetic neurotransmitter.
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Affiliation(s)
- Mingkai Li
- Department of Pharmacology, The Fourth Military Medical University, Xian 710032, PR China
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Zhao CM, Håkanson R, Chen D. Secretory organelles in ECL cells: effects of pharmacological blockade of the gastrin/CCK2 receptor versus its elimination by gene targeting. Inflammopharmacology 2006; 13:75-82. [PMID: 16259729 DOI: 10.1163/156856005774423818] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Histamine-producing ECL cells are numerous in the stomach. They express gastrin/CCK2 receptors and respond to gastrin by releasing histamine. Ultrastructurally, they display numerous and very characteristic secretory organelles: granules, secretory vesicles and microvesicles. This paper focuses on the impact of the gastrin/CCK2 receptor on the ultrastructure of the ECL cells. The effects of pharmacological blockade of the receptor are compared with the effects of receptor elimination following selective gene targeting. Long-term administration of powerful gastrin/CCK2 receptor antagonists was found to induce hypotrophy of rat stomach ECL cells with reduced number of granules, secretory vesicles and microvesicles. In gastrin/CCK2 receptor knockout mice ECL cells, i.e., histamine-storing cells with the characteristic ultrastructure of ECL cells, had disappeared from the oxyntic mucosa and been replaced by a novel population of endocrine-like cells. These cells harbored granules and microvesicles, but were devoid of histamine and secretory vesicles. We suggest that the gastrin/CCK2 receptor is important for the proper differentiation of the ECL cells and for maintaining their characteristic ultrastructure.
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Affiliation(s)
- Chun-Mei Zhao
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
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15
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Abstract
Minute-to-minute behavior of the bowel, whether it is normal or disordered, is determined by integrative functions of the enteric nervous system (ENS). Information input processed by the ENS is derived from local sensory receptors, the central nervous system, and immune/inflammatory cells including mast cells. Enteric mast cells use the power of the immune system for detection of antigenic threats and for long-term memory of the identity of the specific antigens. Specific antibodies attach to the mast cells and enable the mast cell to detect sensitizing antigens when they reappear in the gut lumen. Should the sensitizing antigen reappear, mast cells detect it and signal its presence to the ENS. The ENS interprets the mast cell signal as a threat and calls up from its program library secretory and propulsive motor behavior that is organized to eliminate the threat rapidly and effectively. Operation of the alarm program protects the individual, but at the expense of symptoms that include cramping abdominal pain, fecal urgency, and diarrhea. Enteric mast cells use immunologic memory functions to detect foreign antigens as they appear and reappear throughout the life of the individual. Mast cells use paracrine signaling for the transfer of chemical information to the neural networks of the ENS. Integrative circuits in the ENS receive and interpret the chemical signals from the mast cells. Signals from the mast cells are interpreted by the ENS as a labeled code for the presence of a threat in the intestinal lumen.
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Affiliation(s)
- Jackie D Wood
- Department of Physiology and Cell Biology and Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, USA.
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Zhao CM, Chen D, Dornonville de la Cour C, Lindqvist A, Persson L, Håkanson R. Histamine and histidine decarboxylase are hallmark features of ECL cells but not G cells in rat stomach. ACTA ACUST UNITED AC 2004; 118:61-6. [PMID: 14759558 DOI: 10.1016/j.regpep.2003.10.031] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2003] [Revised: 10/09/2003] [Accepted: 10/15/2003] [Indexed: 10/26/2022]
Abstract
The oxyntic mucosa of the rat stomach is rich in ECL cells which produce and secrete histamine in response to gastrin. Histamine and the histamine-forming enzyme histidine decarboxylase (HDC) have been claimed to occur also in the gastrin-secreting G cells in the antrum. In the present study, we used a panel of five HDC antisera and one histamine antiserum to investigate whether histamine and HDC are exclusive to the ECL cells. By immunocytochemistry, we could show that the ECL cells were stained with the histamine antiserum and all five HDC antisera. The G cells, however, were not stained with the histamine antiserum, but with three of the five HDC antisera. Thus, histamine and HDC coexist in the ECL cells (oxyntic mucosa) but not in G cells (antral mucosa). Western blot analysis revealed a typical pattern of HDC-immunoreactive bands (74, 63 and 54 kDa) in oxyntic mucosa extracts with all five antisera. In antral extracts, immunoreactive bands were detected with three of the five HDC antisera (same as above); the pattern of immunoreactivity differed from that in oxyntic mucosa. Food intake of fasted rats or treatment with the proton pump inhibitor omeprazole raised the HDC activity and the HDC protein content of the oxyntic mucosa but not of the antral mucosa; the HDC activity in the antrum was barely detectable. We suggest that the HDC-like immunoreactivity in the antrum represents a cross-reaction with non-HDC proteins and conclude that histamine and HDC are hallmark features of ECL cells but not of G cells.
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Affiliation(s)
- C-M Zhao
- Department of Medical Technology, Faculty of Technology, Sør-Trøndelag University College, Trondheim, Norway.
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17
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Li M, Luo X, Chen L, Zhang J, Hu J, Lu B. Co-localization of histamine and dopamine-beta-hydroxylase in sympathetic ganglion and release of histamine from cardiac sympathetic terminals of guinea-pig. ACTA ACUST UNITED AC 2003; 23:327-33. [PMID: 15255817 DOI: 10.1111/j.1474-8673.2004.00305.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
1. The aim of this study was to investigate the co-localization of histamine and dopamine-beta-hydroxylase in the superior cervical ganglion of guinea-pig and release of histamine from cardiac sympathetic terminals in guinea-pig isolated atrium. 2. Histidine decarboxylase (a histamine-synthesizing enzyme) mRNA signals were detected in the neurones of superior cervical ganglion of guinea-pig by in situ hybridization. The results of double-labelled immunofluorescence further confirmed the co-localization of histamine and dopamine-beta-hydroxylase in the large principle neurons and small intensely fluorescent cells in the superior cervical ganglion. The immunoreactivities of both histamine and dopamine-beta-hydroxylase were significantly attenuated after 6-hydroxydopamine-induced lesion of sympathetic nerves. 3. The refractory electrical field stimulation caused the release of histamine from cardiac sympathetic terminals of guinea-pig isolated atria (112.14 +/- 40.34 ng x ml(-1)), which was significantly attenuated to 35 +/- 15.57 ng x ml(-1) by reserpine pretreatment. Following administering compound 48/80, a mast cell degranulator, electrical field stimulation induced a dramatic increase of endogenous histamine release from isolated atria (303.57 +/-72.93 ng x ml(-1)). When compound 48/80 was added to the reserpine-treated atria, the release of histamine induced by field stimulation was decreased to 207.14 +/- 76.39 ng x ml(-1). 4 These results provide novel evidence that histamine co-exists with noradrenaline in sympathetic nerves and might act as a neurotransmitter to modulate sympathetic neurotransmission.
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Affiliation(s)
- M Li
- Department of Pharmacology, The Fourth Military Medical University, Xi'an 710032, P R China
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18
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Liu S, Hu HZ, Gao N, Gao C, Wang G, Wang X, Peck OC, Kim G, Gao X, Xia Y, Wood JD. Neuroimmune interactions in guinea pig stomach and small intestine. Am J Physiol Gastrointest Liver Physiol 2003; 284:G154-64. [PMID: 12388180 DOI: 10.1152/ajpgi.00241.2002] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Enteric neuroimmune interactions in gastrointestinal hypersensitivity responses involve antigen detection by mast cells, mast cell degranulation, release of chemical mediators, and modulatory actions of the mediators on the enteric nervous system (ENS). Electrophysiological methods were used to investigate electrical and synaptic behavior of neurons in the stomach and small intestine during exposure to beta-lactoglobulin in guinea pigs sensitized to cow's milk. Application of beta-lactoglobulin to sensitized preparations depolarized the membrane potential and increased neuronal excitability in small intestinal neurons but not in gastric neurons. Effects on membrane potential and excitability in the small intestine were suppressed by the mast cell stabilizing drug ketotifen, the histamine H(2) receptor antagonist cimetidine, the cyclooxygenase inhibitor piroxicam, and the 5-lipoxygenase inhibitor caffeic acid. Unlike small intestinal ganglion cells, gastric myenteric neurons did not respond to histamine applied exogenously. Antigenic exposure suppressed noradrenergic inhibitory neurotransmission in the small intestinal submucosal plexus. The histamine H(3) receptor antagonist thioperamide and piroxicam, but not caffeic acid, prevented the allergic suppression of noradrenergic inhibitory neurotransmission. Antigenic stimulation of neuronal excitability and suppression of synaptic transmission occurred only in milk-sensitized animals. Results suggest that signaling between mast cells and the ENS underlies intestinal, but not gastric, anaphylactic responses associated with food allergies. Histamine, prostaglandins, and leukotrienes are paracrine signals in the communication pathway from mast cells to the small intestinal ENS.
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Affiliation(s)
- Sumei Liu
- Department of Physiology and Cell Biology, Ohio State University, College of Medicine and Public Health, Columbus 43210, USA
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19
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Kitanaka J, Kitanaka N, Tsujimura T, Terada N, Takemura M. Expression of diamine oxidase (histaminase) in guinea-pig tissues. Eur J Pharmacol 2002; 437:179-85. [PMID: 11890907 DOI: 10.1016/s0014-2999(02)01302-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The expression of mRNA for diamine oxidase (histaminase) and the enzyme activity in guinea-pig tissues were investigated. Reverse transcription-polymerase chain reaction analysis revealed that the message corresponding to the long form present in humans and rats was expressed abundantly in the small intestine and liver. Small but detectable amounts of diamine oxidase mRNA were observed in the kidney, stomach, cerebellum, thalamus+hypothalamus, and cerebral cortex. Northern blot analysis showed that the message (2.8 kb in size) was observed abundantly in the liver and small intestine and was detectable in the kidney and stomach but not in the brain or lung. In situ hybridization showed that diamine oxidase mRNA was localized throughout the liver and epithelial cells of the small intestine. Diamine oxidase activity was detected at various levels in different tissues of the guinea-pig at the following relative abundance: liver>small intestine>lung, kidney>stomach. Histamine dose-dependently induced the contraction of sections of the guinea-pig small intestine, and the pretreatment of the tissue section with aminoguanidine (100 microM), a diamine oxidase inhibitor, but not with S-[4-(N,N-dimethylamino)butyl]isothiourea (100 microM), an inhibitor of histamine N-methyltransferase, shifted the dose-response curve of histamine-induced contraction to lower concentrations. These results suggest that diamine oxidase has a crucial role in the degradation of histamine in the guinea-pig small intestine and probably in the liver.
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Affiliation(s)
- Junichi Kitanaka
- Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
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20
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Lazarov NE. Comparative analysis of the chemical neuroanatomy of the mammalian trigeminal ganglion and mesencephalic trigeminal nucleus. Prog Neurobiol 2002; 66:19-59. [PMID: 11897404 DOI: 10.1016/s0301-0082(01)00021-1] [Citation(s) in RCA: 191] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
A characteristic peculiarity of the trigeminal sensory system is the presence of two distinct populations of primary afferent neurons. Most of their cell bodies are located in the trigeminal ganglion (TG) but part of them lie in the mesencephalic trigeminal nucleus (MTN). This review compares the neurochemical content of central versus peripheral trigeminal primary afferent neurons. In the TG, two subpopulations of primary sensory neurons, containing immunoreactive (IR) material, are identified: a number of glutamate (Glu)-, substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)-, cholecystokinin (CCK)-, somatostatin (SOM)-, vasoactive intestinal polypeptide (VIP)- and galanin (GAL)-IR ganglion cells with small and medium-sized somata, and relatively less numerous larger-sized neuropeptide Y (NPY)- and peptide 19 (PEP 19)-IR trigeminal neurons. In addition, many nitric oxide synthase (NOS)- and parvalbumin (PV)-IR cells of all sizes as well as fewer, mostly large, calbindin D-28k (CB)-containing neurons are seen. The majority of the large ganglion cells are surrounded by SP-, CGRP-, SOM-, CCK-, VIP-, NOS- and serotonin (SER)-IR perisomatic networks. In the MTN, the main subpopulation of large-sized neurons display Glu-immunoreactivity. Additionally, numerous large MTN neurons exhibit PV- and CB-immunostaining. On the other hand, certain small MTN neurons, most likely interneurons, are found to be GABAergic. Furthermore, NOS-containing neurons can be detected in the caudal and the mesencephalic-pontine junction portions of the nucleus. Conversely, no immunoreactivity to any of the examined neuropeptides is observed in the cell bodies of MTN neurons but these are encircled by peptidergic, catecholaminergic, serotonergic and nitrergic perineuronal arborizations in a basket-like manner. Such a discrepancy in the neurochemical features suggests that the differently fated embryonic migration, synaptogenesis, and peripheral and central target field innervation can possibly affect the individual neurochemical phenotypes of trigeminal primary afferent neurons.
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Affiliation(s)
- Nikolai E Lazarov
- Department of Anatomy, Faculty of Medicine, Thracian University, 11 Armejska Street, BG-6003 Stara Zagora, Bulgaria.
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21
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Lindström E, Chen D, Norlén P, Andersson K, Håkanson R. Control of gastric acid secretion:the gastrin-ECL cell-parietal cell axis. Comp Biochem Physiol A Mol Integr Physiol 2001; 128:505-14. [PMID: 11246041 DOI: 10.1016/s1095-6433(00)00331-7] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Gastric acid secretion is under nervous and hormonal control. Gastrin, the major circulating stimulus of acid secretion, probably does not stimulate the parietal cells directly but acts to mobilize histamine from the ECL cells in the oxyntic mucosa. Histamine stimulates the parietal cells to secrete HCl. The gastrin-ECL cell pathway has been investigated extensively in situ (gastric submucosal microdialysis), in vitro (isolated ECL cells) and in vivo (intact animals). Gastrin acts on CCK2 receptors to control the synthesis of ECL-cell histamine, accelerating the expression of the histamine-forming enzyme histidine decarboxylase (HDC) at both the transcription and the translation/posttranslation levels. Depletion of histamine by alpha-fluoromethylhistidine (an irreversible inhibitor of HDC) prevents gastrin-induced but not histamine-induced gastric acid secretion. Acute CCK2 receptor blockade inhibits gastrin-evoked but not histamine-induced acid secretion. Studies both in vivo/in situ and in vitro have suggested that while acetylcholine seems capable of activating parietal cells, it does not affect histamine secretion from ECL cells. Unlike acetylcholine, the neuropeptides pituitary adenylate cyclase-activating peptide and vasoactive intestinal peptide mobilize ECL-cell histamine. Whether vagally stimulated acid secretion reflects an effect of the enteric nervous system on the ECL cells (neuropeptides) and/or a direct one on the parietal cells needs to be further investigated.
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Affiliation(s)
- E Lindström
- Department of Pharmacology, Institute of Physiological Sciences, University of Lund, Lund, Sweden
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22
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Tahara A, Nishibori M, Ohtsuka A, Sawada K, Sakiyama J, Saeki K. Immunohistochemical localization of histamine N-methyltransferase in guinea pig tissues. J Histochem Cytochem 2000; 48:943-54. [PMID: 10858271 DOI: 10.1177/002215540004800707] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Histamine plays important roles in gastric acid secretion, inflammation, and allergic response. Histamine N-methyltransferase (HMT; EC 2.1.1.8) is crucial to the inactivation of histamine in tissues. In this study we investigated the immunohistochemical localization of this enzyme in guinea pig tissues using a rabbit polyclonal antibody against bovine HMT. The specificity of the antibody for guinea pig HMT was confirmed by Western blotting and the lack of any staining using antiserum preabsorbed with purified HMT. There was strong HMT-like immunoreactivity (HMT-LI) in the epithelial cells in the gastrointestinal tract, especially in the gastric body, duodenum, and jejunum. The columnar epithelium in the gallbladder was also strongly positive. Almost all the myenteric plexus from the stomach to the colon was stained whereas the submucous plexus was not. Other strongly immunoreactive cells included the ciliated cells in the trachea and the transitional epithelium of the bladder. Intermediately immunoreactive cells included islets of Langerhans, epidermal cells of the skin, alveolar cells in the lung, urinary tubules in the kidney, and epithelium of semiferous tubules. HMT-LI was present in specific structures in the guinea pig tissues. The widespread distribution of HMT-LI suggests that histamine has several roles in different tissues.
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Affiliation(s)
- A Tahara
- Department of Pharmacology, Okayama University Medical School, Okayama, Japan
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23
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Yokotani K, Murakami Y, Okada S, Wang M, Nakamura K. Histamine H(3) receptor-mediated inhibition of endogenous acetylcholine release from the isolated, vascularly perfused rat stomach. Eur J Pharmacol 2000; 392:23-9. [PMID: 10748268 DOI: 10.1016/s0014-2999(00)00085-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
We studied the effects of histamine H(3) receptor ligands on the release of endogenous acetylcholine from the isolated, vascularly perfused rat stomach. The stomach was perfused via the celiac artery with modified Krebs-Ringer solution containing physostigmine. Released acetylcholine from the portal vein was electrochemically measured using high-performance liquid chromatography and an enzyme system. Vagus nerves were electrically stimulated twice for 2 min (0.5 or 2.5 Hz). Acetylcholine release evoked at 2.5 Hz was slightly inhibited by histamine and effectively potentiated by thioperamide, a histamine H(3) receptor antagonist. Acetylcholine release evoked at 0.5 Hz in the presence of atropine was not influenced by thioperamide, but effectively inhibited by histamine, R-alpha-methylhistamine or imetit, histamine H(3) receptor agonists. These inhibitory effects were abolished by thioperamide or pertussis toxin. These results suggest that histamine attenuates acetylcholine release from vagus nerves through histamine H(3) receptor-mediated and pertussis toxin-sensitive mechanisms in the rat stomach.
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Affiliation(s)
- K Yokotani
- Department of Pharmacology, Kochi Medical School, Nankoku, Kochi, Japan
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24
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Hunyady B, Palkovits M, Mezey E. Vesicular monoamine transporters in the rat stomach. JOURNAL OF PHYSIOLOGY, PARIS 2000; 94:123-30. [PMID: 10791693 DOI: 10.1016/s0928-4257(00)00152-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
Cellular distribution of vesicular monoamine transporters (VMATs), known to regulate vesicular storage and release of biogenic amines (i.e., catecholamines, serotonin, histamine, etc.), have been studied in the rat stomach using in situ hybridization histochemistry (ISHH) and immunohistochemical (IHC) techniques. 35S-UTP labeled riboprobes showed that mRNAs of both VMATs are expressed in the gastric mucosa. A combination of ISHH and IHC verified that most of the parietal cells (among other epithelial cells) express mRNA of the peripheral type transporter (VMAT1) while enterochromaffin-like cells (ECL) of the fundic mucosa express mRNA of the central type (VMAT2). In addition, with double fluorescent IHC we detected VMAT1 protein in serotoninergic enterochromaffin cells (EC) of the stomach and in gastrin producing G cells of the antral mucosa. Similarly to the fundus, VMAT2 protein was present in ECL cells and in the enteric plexus. Surprisingly, serotonin- and/or histamine-containing cells in the connective tissue compartments of the stomach (i.e., lamina propria and submucosa), immunoreactive for a mast cell specific antigen, displayed neither VMATI nor VMAT2 immunoreactivity. Distribution of VMATs in the rat stomach support our previous observations on aminergic properties of two important gastrointestinal (GI) epithelial cell populations primarily known for other specific secretory products, i.e. dopaminergic properties of acid producing parietal cells and histaminergic properties of gastrin producing G cells. These data emphasize the existence of a non-neuronal, intrinsic aminergic system in the GI tract.
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Affiliation(s)
- B Hunyady
- First Department of Medicine, Medical University of Pécs, Hungary
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25
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Kashiba H, Fukui H, Morikawa Y, Senba E. Gene expression of histamine H1 receptor in guinea pig primary sensory neurons: a relationship between H1 receptor mRNA-expressing neurons and peptidergic neurons. BRAIN RESEARCH. MOLECULAR BRAIN RESEARCH 1999; 66:24-34. [PMID: 10095074 DOI: 10.1016/s0169-328x(98)00346-5] [Citation(s) in RCA: 75] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Pharmacological studies have suggested that a subgroup of primary sensory neurons is responsive to histamine via the histamine H1 receptor. We addressed this issue using in situ hybridization histochemistry with a cRNA probe for the guinea pig H1 receptor gene. About 15% of the trigeminal and lumber dorsal root ganglion (DRG) neurons, but none of nodose ganglion neurons, were intensely labeled with this probe. The H1 receptor mRNA-positive neurons were exclusively small in size, and were demonstrated to give rise to unmyelinated fibers by ultrastructural analysis of isolectin B4-labeling. However, the H1 receptor mRNA-expressing DRG neurons were not immunoreactive to substance P (SP) and calcitonin gene-related peptide (CGRP). A marked increase in the number of mRNA-positive DRG neurons were observed 1-5 days after a crush injury of the sciatic nerve (3-4-fold of the control value). These neurons turned mRNA-positive after the nerve crush were also mainly small-sized. The mRNA signals were detected in many peptidergic (SP/CGRP) neurons, in contrast to the normal state. On the other hand, in the neurons which showed intense labeling in the normal condition, the mRNA signals were down-regulated. These results suggest that primary sensory neurons include two kinds of H1 receptor-expressing sensory neurons, one expressing H1 receptor mRNAs in the normal state and the other up-regulating the mRNAs following the peripheral nerve damage.
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Affiliation(s)
- H Kashiba
- Department of Physiology, Kansai College of Oriental Medicine, 2-11-1 Wakaba, Kumatori, Sennan, Osaka 590-0433, Japan
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26
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Tsai LH, Lee YJ, Wu J. Effect of excitatory amino acid neurotransmitters on acid secretion in the rat stomach. J Biomed Sci 1999; 6:36-44. [PMID: 9933741 DOI: 10.1007/bf02256422] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Excitatory amino acids (EAAs), in particular, L-aspartate (L-Asp) neurons and their processes, were localized in the rat stomach using a immunohistochemical method with specific antibodies against either L-Asp or its synthesizing enzyme, aspartate aminotransferase (AAT). Myenteric ganglia and nerve bundles in the circular muscle and in the longitudinal muscle were found to be AAT- or L-Asp-positive. In addition, AAT- or L-Asp-positive cells were also found in the muscle layer and the deep mucosal layer. The distribution of AAT- or L-Asp-positive cells in both the mucosal and muscle layers was heterogeneous in the stomach. In addition, L-Asp at 10(-6) M negligibly influenced acid secretion in an everted preparation of isolated rat stomach. However, according to our results, L-Asp markedly inhibited the histamine-stimulated acid secretion, but not the oxotremorine- or the pentagastrin-stimulated acid secretion. Furthermore, L-Asp also inhibited histamine-induced elevation of cAMP. L- Asp itself did not affect the cAMP level although it elevated the cGMP level in the stomach. Moreover, either (+)2-amino-5-phosphonovaleric acid or (+/-)3-(2-carboxypiperazin-4-yl)prophyl-1-phosphonic acid, i.e. two specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors, blocked the inhibitory effect of L-Asp on histamine-stimulated acid secretion or histamine-induced elevation of cAMP. Since cAMP has been strongly implicated as the second messenger involved in histamine-induced acid secretion, we believe that L-Asp regulates acid secretion in the stomach by inhibiting histamine release through the NMDA receptors, subsequently lowering the level of cAMP and ultimately reducing acid secretion.
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Affiliation(s)
- L H Tsai
- Department of Physiology, School of Medicine, Taipei Medical College, Taipei, Taiwan, ROC.
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27
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Doi T, Terai K, Tooyama I, Sakata T, Kimura H. Production of monoclonal antibody against histamine and its application to immunohistochemical study in the stomach. THE HISTOCHEMICAL JOURNAL 1998; 30:425-34. [PMID: 10192542 DOI: 10.1023/a:1003224326578] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
A monoclonal antibody against histamine has been produced. A histamine-haemocyanin conjugate prepared using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a coupling agent was used for immunizing mice. Immunized mice were sacrificed to prepare monoclonal antibody using a hybridoma technique. On immunospot assay, the hybridoma culture supernatant containing a monoclonal antibody was capable of detecting 50 pmol of histamine. Using this antibody, we examined the cellular localization of histamine-like immunoreactivity in the stomach of normal or alpha-fluoromethylhistidine-treated rats and mice. Immunoreactive cells were abundant in the gastric mucosal layer. These positive cells were often located in the basal half of the fundic gland but were rare in the pyloric gland. The cells, small or medium in size, spindle or cone in shape, were intermingled with immunonegative epithelial cells. In the cytoplasm of the positive cells, granular reaction products were densely deposited. In addition, a few positive cells, identified as mast cells by Toluidine Blue staining, were distributed mainly in the submucosal and muscular layer. The antibody preabsorbed with 10 mM histamine gave no positive immunostaining. For pharmacological study, some rats were injected six times with c-fluoromethylhistidine every 8 h. In these rats, positive cells except mast cells were no longer detected. In conclusion, the monoclonal antibody produced appears to be highly specific for histamine. Its application in immunohistochemistry should provide a powerful tool for analysing the roles of histamine in enterochromaffin-like or mast cells in the stomach.
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Affiliation(s)
- T Doi
- Division of Neuroanatomy, Institute of Molecular Neurobiology, Shiga University of Medical Science, Otsu, Japan
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28
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Campos HA, Montenegro M. Footshock-induced rise of rat blood histamine depends upon the activation of postganglionic sympathetic neurons. Eur J Pharmacol 1998; 347:159-64. [PMID: 9653876 DOI: 10.1016/s0014-2999(98)00097-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
We have previously shown the existence of a novel peripheral reflex inhibitorily modulating the vas deferens sympathetic activity. An interaction between noradrenergic and histamine-containing neurons is involved in this reflex. As an overall mechanism of sympathetic autoregulation, we found that enhanced sympathetic activity in the rat during the stress induced by brief inescapable footshocks caused a marked rise of blood histamine that was seemingly dependent upon sympathetic activity. This rise was prevented by either previous ganglionic blockade with hexamethonium or chronic guanethidine-induced sympathectomy. Previous adrenal demedullation did not impair this rise. Thus, it appears that only the sympathetic postganglionic neuron, interacting with a histamine-containing neuron, is involved in the rise of blood histamine induced by footshocks.
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Affiliation(s)
- H A Campos
- Department of Pharmacology, Vargas Medical School, Central University of Venezuela, Caracas
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29
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Lindström E, Björkqvist M, Boketoft A, Chen D, Zhao CM, Kimura K, Håkanson R. Neurohormonal regulation of histamine and pancreastatin secretion from isolated rat stomach ECL cells. REGULATORY PEPTIDES 1997; 71:73-86. [PMID: 9416989 DOI: 10.1016/s0167-0115(97)01018-5] [Citation(s) in RCA: 86] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
ECL cells are numerous in the acid-producing part of the rat stomach. They are rich in histamine and pancreastatin, a chromogranin A-derived peptide, and they secrete these products in response to gastrin. We have examined how isolated ECL cells respond to a variety of neuromessengers and peptide hormones. Highly purified (85%) ECL cells were collected from rat stomach using repeated counter-flow elutriation and cultured for 48 h before experiments were conducted. The ECL cells responded to gastrin, sulphated cholecystokinin-8 and to high K+ and Ca2+ with the parallel secretion of histamine and pancreastatin. Glycine-extended gastrin was without effect. Forskolin, an activator of adenylate cyclase, induced secretion, whereas isobutylmethylxanthine, a phosphodiesterase inhibitor, raised the basal release without enhancing the gastrin-evoked stimulation. Maximum stimulation with gastrin resulted in the release of 30% of the secretory products. Numerous neuromessengers and peptide hormones were screened for their ability to stimulate secretion and to inhibit gastrin-stimulated secretion. Pituitary adenylate cyclase activating peptide (PACAP)-27 and -38 stimulated secretion of both histamine and pancreastatin with a potency greater than that of gastrin and with the same efficacy. Related peptides, such as vasoactive intestinal peptide, helodermin and helospectin, stimulated secretion with lower potency. The combination of EC100 gastrin and EC50 PACAP produced a greater response than gastrin alone. None of the other neuropeptides or peptide hormones tested stimulated secretion. Serotonin, adrenaline, noradrenaline and isoprenaline induced moderate secretion at high concentrations. Muscarinic receptor agonists did not stimulate secretion, and histamine and selective histamine receptor agonists and antagonists were without effect. This was the case also with GABA, aspartate and glutamate. Somatostatin and galanin, but none of the other agents tested, inhibited gastrin-stimulated secretion. Our results reveal that not only gastrin but also PACAP is a powerful excitant of the ECL cells, that not only somatostatin, but also galanin can suppress secretion, that muscarinic receptor agonists fail to evoke secretion, and that histamine (and pancreastatin) does not evoke autofeedback inhibition.
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Affiliation(s)
- E Lindström
- Department of Pharmacology, University of Lund, Sweden
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30
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Vesicular monoamine transporter 2 expression in enteric neurons and enterochromaffin-like cells of the rat. Neurosci Lett 1996. [DOI: 10.1016/0304-3940(96)13051-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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31
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Nagy JI, Yamamoto T, Uemura H, Schrader WP. Adenosine deaminase in rodent median eminence: detection by antibody to the mouse enzyme and co-localization with adenosine deaminase-complexing protein (CD26). Neuroscience 1996; 73:459-71. [PMID: 8783262 DOI: 10.1016/0306-4522(96)00049-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Adenosine deaminase in the hypothalamic tuberomammillary nucleus and median eminence of rat and mouse brains was investigated with two different antibodies generated against the enzyme derived from either calf or mouse. Both antibodies labelled neurons in the tuberomammillary nucleus and, as determined in rat, they immunolabelled the same neurons. In the median eminence, immunopositive fibres and terminals were detected with anti-mouse adenosine deaminase in both rat and mouse, while no such staining was seen in either species with antibody against the calf enzyme. These fibres were most concentrated in the external median eminence, had a more restricted distribution than those containing either galanin or tyrosine hydroxylase and only partially overlapped with oxytocin-positive fibres. By electron microscopy, adenosine deaminase was found in terminals containing both small, clear vesicles with diameters of 35 to 45 nm and large dense-core vesicles with diameters of 100 to 140 nm. Preadsorption of antibodies with purified enzyme derived from the species against which they were directed eliminated all staining in rat, while antibody adsorptions across species were less effective. Preadsorption of anti-mouse adenosine deaminase antibody with the mouse deaminase led to increased labelling in mouse median eminence, suggesting an interaction between tissue components and antibody-linked enzyme. Tests for the presence of adenosine deaminase-complexing protein (CD26) with an antibody against this protein gave positive labelling in the median eminence of both species and this labelling was co-distributed with that seen for adenosine deaminase. These results confirm the expression of adenosine deaminase in restricted populations of neurons in rodent brain as revealed with a novel antibody, suggest the presence of a distinct form or localization of the enzyme in the median eminence, and raise the possibility that it contributes, perhaps along with CD26, to purinergic regulation of hormone secretion in this structure.
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Affiliation(s)
- J I Nagy
- Department of Physiology, University of Manitoba, Winnipeg, Canada
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32
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Johansson O, Virtanen M, Hilliges M. Histaminergic nerves demonstrated in the skin. A new direct mode of neurogenic inflammation? Exp Dermatol 1995; 4:93-6. [PMID: 7543795 DOI: 10.1111/j.1600-0625.1995.tb00229.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
An intradermal administration of histamine into human skin results in a local erythema, edema and often also the sensations of itch and/or pain. These effects have classically been attributed to the presence of histamine-containing mast cells. However, in the present investigation, we report the observation of histamine-immunoreactive nerves in the skin of Sprague-Dawley rats using a new and highly sensitive immunohistochemical approach. These data suggest a more direct route of cutaneous histamine effects, mediated exclusively by the peripheral nervous system. The findings could also give a new basis for explaining histamine-related issues, such as itch.
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Affiliation(s)
- O Johansson
- Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
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Frieling T, Palmer JM, Cooke HJ, Wood JD. Neuroimmune communication in the submucous plexus of guinea pig colon after infection with Trichinella spiralis. Gastroenterology 1994; 107:1602-9. [PMID: 7525397 DOI: 10.1016/0016-5085(94)90798-6] [Citation(s) in RCA: 72] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND/AIMS Enteric neuroimmune communication in gastrointestinal hypersensitivity responses includes antigen detection by mast cells and release of chemical messages to the enteric nervous system. The aim of this study was to analyze the electrical and synaptic behavior of neurons in the colonic submucous plexus during exposure to Trichinella spiralis antigen in animals infected earlier with the parasite. METHODS Microelectrodes were used to record in submucous neurons of guinea pig distal colon during application of Trichinella antigen. RESULTS Neurons in sensitized animals were more excitable than in controls. Hyperexcitability was seen as a greater probability of spontaneous action potential discharge and repetitive firing to depolarizing current or exposure to acetylcholine. Application of histaminergic antagonists reversed the augmented excitability, suggesting endogenously released histamine as a responsible factor. Antigenic exposure increased neuronal excitability and suppressed nicotinic transmission at fast cholinergic synapses only in sensitized animals. Effects on excitability, but not presynaptic inhibitory effects, were blocked by cimetidine. CONCLUSIONS Signaling between mucosal mast cells and the enteric nervous system is involved in colonic anaphylactic responses to sensitizing antigens. Histamine is a paracrine signal in the communication pathway.
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Affiliation(s)
- T Frieling
- Department of Physiology, College of Medicine, Ohio State University, Columbus
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Tielemans Y, Håkanson R, Willems G. Hyperplastic manifestations of enterochromaffin-like cells in the stomach of rats with congenital moderate hypergastrinemia. Scand J Gastroenterol 1994; 29:219-25. [PMID: 8209180 DOI: 10.3109/00365529409090467] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The effect of moderate congenital hypergastrinemia on the enterochromaffin-like (ECL) cells was investigated in Zucker rats 4 and 18 months of age by combining autoradiography after tritiated thymidine injection and selective immunocytochemistry. In both age groups the serum gastrin concentration was 200% higher in obese (fa/fa) than in lean (Fa/Fa; Fa/fa) littermates. In 4-month-old obese rats there was a 120% increase (p < 0.05) in the ECL cell labeling index and also a moderate increase in the ECL cell density (p < 0.05) compared with lean controls. In 18-month-old obese rats the hyperplasia was quantitatively more prominent, with both linear and micronodular ECL cell hyperplasia. At this stage, the ECL cell labeling indices in obese and in lean animals were similar. These data support the hypothesis that moderate hypergastrinemia initially accelerates the ECL cell proliferation rate, leading to diffuse ECL cell hyperplasia. In similar conditions, at the latter stage, linear and micronodular ECL cell hyperplasia also develop in most of the hypergastrinemic animals.
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Affiliation(s)
- Y Tielemans
- Dept. of Surgery and Cancer Research Unit, Vrije Universiteit Brussel, Belgium
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35
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Borges R. Histamine H1 receptor activation mediates the preferential release of adrenaline in the rat adrenal gland. Life Sci 1994; 54:631-40. [PMID: 7509435 DOI: 10.1016/0024-3205(94)00869-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Histamine elicited the release of catecholamines from "in vitro" perfused rat adrenals with an EC50 of 3 microM. This concentration was in the same range as those which caused a fall in the arterial blood pressure when infused intravenously in anaesthetized rats. Histamine stimulation was potently blocked by dexclorfeniramine (IC50 = 300 pM), but unaffected by ranitidine, suggesting the involvement of H1 receptors. Histamine release preferentially adrenaline. Mast cells were not detected within adrenal medulla by histochemical techniques. Compound 48/80 did not trigger catecholamine release. Catecholamine secretion evoked by splanchnic nerves stimulation was not modified by a combination of H1 and H2 antagonists. In conclusion, the histamine that elicited adrenaline release from rat adrenals comes from blood circulation not from local mast cells or splanchnic nerves. These effects are mediated through the activation of H1 receptors.
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Affiliation(s)
- R Borges
- Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain
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37
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Brenna E, Waldum HL. Trophic effect of gastrin on the enterochromaffin like cells of the rat stomach: establishment of a dose response relationship. Gut 1992; 33:1303-6. [PMID: 1446849 PMCID: PMC1379593 DOI: 10.1136/gut.33.10.1303] [Citation(s) in RCA: 87] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Gastrin was given to rats by continuous subcutaneous infusion through implanted osmotic minipumps in doses covering a wide range of the dose response relationship for gastrin with regard to the trophic effect on the enterochromaffin like cells of the oxyntic mucosa. Thirty five rats were divided into five groups (each of seven rats), one group receiving a control solution of 1% albumin, the others receiving gastrin in 1% albumin at doses of 2.5, 5, 10, and 15 micrograms/kg/h, respectively. The plasma gastrin concentrations in the various groups increased in the same order of magnitude as expected from the gastrin doses given. Gastrin induced a dose dependent increase in enterochromaffin like cell density, oxyntic mucosal histamine concentration and histidine decarboxylase activity up to the dose of 5 micrograms/kg/h, where the increase levelled off. Hence, the dose response relationship for the trophic effect of gastrin on the enterochromaffin like cells seems to follow a polynomial rather than a linear function. These findings may also contribute to the understanding of the trophic effect of gastrin on enterochromaffin like cells in man with conditions associated with hypergastrinaemia.
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Affiliation(s)
- E Brenna
- Institute of Cancer Research, Trondheim, Norway
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38
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Expression ofl-histidine decarboxylase (HDC) mRNA in rat stomach. Inflamm Res 1992. [DOI: 10.1007/bf01997376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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39
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Johansson O, Virtanen M, Hilliges M, Yang Q. Histamine immunohistochemistry: a new and highly sensitive method for studying cutaneous mast cells. THE HISTOCHEMICAL JOURNAL 1992; 24:283-7. [PMID: 1607297 DOI: 10.1007/bf01046843] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Mast cells have characteristic granulae containing various glucoseaminoglycans, proteases and amines (predominantly histamine). The conventional histological methods for studying mast cells are based upon acidic ortho- and metachromatic routine stains of the glucoseaminoglycans. However, the success of these procedures is dependent upon both the fixatives and the tissues used. In this study, we wanted to find out whether an immunohistochemical procedure could overcome some of these difficulties. Normal human skin was fixed in five different types of fixative and processed for indirect immunofluorescence, using an antiserum to histamine. Only one, 4% carbodiimide in 0.1 M phosphate buffer (pH 7.4), resulted in immunostaining. The quality of the staining was good, with a high signal-to-noise ratio, and was located on the mast cells. The method made it possible to visualize small structures such as a single secreted granula, the thin cytoplasmatic extension of some cells, and a previously undescribed dendritic morphology of some of the mast cells. We therefore recommend this procedure for cellular studies of mast cells when accuracy is needed.
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Affiliation(s)
- O Johansson
- Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden
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40
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Nissinen MJ, Håkanson R, Panula P. Ontogeny of histamine-immunoreactive cells in rat stomach. Cell Tissue Res 1992; 267:241-9. [PMID: 1600561 DOI: 10.1007/bf00302961] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
An antiserum against hemocyanin-conjugated histamine was used to study the cellular stores of histamine in the stomach, especially the oxyntic mucosa, of fetal and early postnatal rats. Tissues were fixed in 4% 1-ethyl-3(3-dimethyl-aminopropyl) carbodiimide (EDC-DI) and standard immunofluorescence technique was used. Histamine was first detected on the 16th embryonic (E16) day when a few histamine-immunoreactive (HA-ir) cells and nerve fibers were observed in the muscular layer of the stomach wall. On day E18, HA-ir cells were visualized for the first time in the oxyntic mucosa of the stomach, and from that day on the number of such cells increased slowly initially and after day E20 more rapidly. At birth many of the HA-ir cells in the oxyntic mucosa possessed processes giving them a paracrine-like appearance typical of enterochromaffin-like cells (ECL cells). Only a very small number of the HA-ir cells represented metachromatically stained mast cells and were located in the submucosa. After birth, the number of HA-ir ECL cells increased steadily, until day 21 when the distribution and number was very similar to that of the adult. The results suggest that histamine-containing neurons and ECL cells appear in the stomach wall before birth, and that there are histamine-containing ECL cells in the mucosa and mast cells in the submucosa of the stomach wall at birth.
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Affiliation(s)
- M J Nissinen
- Department of Anatomy, University of Helsinki, Finland
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41
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Nissinen MJ, Castrèn E, Holthöfer H, Panula P. Distribution of histamine in the rat kidney during pregnancy and development. Cell Tissue Res 1992; 267:233-9. [PMID: 1600560 DOI: 10.1007/bf00302960] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
An antiserum against conjugated histamine and two oligonucleotide probes that detect the mRNA encoding L-histidine decarboxylase (HDC) involved in histamine synthesis were used to study the appearance of histamine and its location in the kidneys of fetal, newborn and young postnatal rats and in the kidneys of pregnant rats. On embryonic days 16 and 18 (E16 and E18), some HA-immunoreactive (HA-ir) cells were found within the largest S-shaped bodies. Histamine was found to appear rapidly between the 18th and 20th embryonic days in the convoluted tubules of the kidneys. On postnatal day 0 (P0), the distal convoluted tubules and collecting ducts exhibited bright fluorescence, the intensity of which decreased quickly so that it was faint on day P4 and absent at later stages. In kidneys of pregnant rats HA-ir was found in the epithelium of both the Bowman's capsule, collecting ducts and in a few cells within the tubules. Nonuniform HA-ir was also detected within glomeruli. No evidence for the presence of L-histidine decarboxylase mRNA in kidneys of fetuses or pregnant rats was seen. It is concluded that distinct structures in the developing rat kidney contain histamine during a period around birth from day E20 to day P4. In the pregnant rat, the epithelium that is in direct contact with the urine flow is immunoreactive for histamine from day 16 to 20 of pregnancy. The results suggest that histamine is not synthesized locally in the kidneys but rather originates from other tissues.
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Affiliation(s)
- M J Nissinen
- Department of Anatomy, University of Helsinki, Finland
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Abstract
Rat gastric mucosal cells isolated by enzyme dispersion were separated by elutriation centrifugation. The amount of histamine and the number of enterochromaffin-like (ECL) cells and parietal cells were determined in the crude mucosal cells and the various elutriation fractions. The mucosal cells contained 2.6% ECL and 20% parietal cells. Elutriation centrifugation resulted in good separation of parietal cells and ECL cells. Most of the ECL cells were elutriated in the small cell fractions. Scattered ECL cells were also present in the fraction enriched with parietal cells. Histamine and carbacholine stimulated aminopyrine uptake in a concentration-dependent manner with about the same efficacy, 5.6 times the base-line value. When combined with the phosphodiesterase inhibitor isobutyl methylxanthine, the maximal histamine stimulation was increased to 16.8 times the base-line value, and the sensitivity increased about 10-fold. Gastrin at high and unphysiologic concentrations stimulated only faintly the aminopyrine uptake in parietal cells and the histamine release from ECL cells.
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Affiliation(s)
- E Brenna
- Institute of Cancer Research, University Hospital, Trondheim, Norway
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43
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Nässel DR, Pirvola U, Panula P. Histaminelike immunoreactive neurons innervating putative neurohaemal areas and central neuropil in the thoraco-abdominal ganglia of the flies Drosophila and Calliphora. J Comp Neurol 1990; 297:525-36. [PMID: 2117027 DOI: 10.1002/cne.902970406] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The fused thoraco-abdominal ganglia of the flies Calliphora vomitoria and Drosophila melanogaster were investigated immunocytochemically with antisera against histamine. In both insect species, 18 histaminelike immunoreactive (HA-IR) neurons were resolved in these ganglia. Six of these neurons have cell bodies in the thoracic neuromeres and 12 in the fused abdominal neuromeres. All cell bodies are situated ventrally. In Calliphora all cell bodies are arranged in a segmental pattern. In Drosophila only the thoracic cell bodies have a segmental arrangement, whereas the abdominal ones are clustered anteriorly close to the last thoracic neuromere. In both species the six thoracic neurons supply processes to the synaptic neuropil in the thoracic neuromeres and to the dorsal neural sheath. The processes in the neural sheath run anteriorly in the lateral portions of the ganglion into the cervical connective. In a few regions laterally arborizing terminals are found in putative neurohaemal areas. These areas were investigated by electron microscopic immunocytochemistry in Calliphora. The HA-IR terminals (containing small granular vesicles) were found outside the "blood-brain barrier" below the acellular basal lamina of the neural sheath. Release of histamine into the circulation is therefore theoretically possible. The central processes of the six thoracic HA-IR neurons may interact synaptically with large numbers of other neurons in the neuropil, and the peripheral varicose fibers from the same HA-IR neurons possibly are neurohaemal release sites. The abdominal HA-IR neurons, in contrast, form extensive arborizations within the synaptic neuropil only. Both thoracic and abdominal neurons have ipsilateral and contralateral branches as well as processes that invade more than one neuromere. A single HA-IR neuron thus invades large volumes of synaptic neuropil. Histamine may be used by neurons of the ventral ganglia both as neurotransmitter (or neuromodulator) and as a circulating neurohormone released from the neural sheath.
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Affiliation(s)
- D R Nässel
- Department of Zoology, University of Stockholm, Sweden
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44
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Wikgren M, Reuter M, Gustafsson MK, Lindroos P. Immunocytochemical localization of histamine in flatworms. Cell Tissue Res 1990; 260:479-84. [PMID: 2372807 DOI: 10.1007/bf00297227] [Citation(s) in RCA: 32] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Specific antibodies against histamine were used to demonstrate the occurrence and cellular distribution of histamine-like immunoreactivity in three species of flatworms (phylum Platyhelminthes). In the parasitic cestode Diphyllobothrium dendriticum, histamine-reactivity was found in neurons of the main nerve cords, and in cells lining the central and peripheral excretory ducts. In the free-living microturbellarian Microstomum lineare and in the planarian Polycelis nigra, histamine-immunoreactivity was restricted to cells and fibres of the nervous system. The occurrence of histamine or a related substance in the nervous system of flatworms, which represent primary bilateria, indicates the importance of this neuroactive substance in the animal kingdom.
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Affiliation(s)
- M Wikgren
- Department of Biology, Abo Akademi, Finland
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Abstract
Histamine and chromogranin A-immunoreactive cells were studied in the mucosa of the human stomach. Cells reacting to both histamine and chromogranin A-antibodies (histamine containing endocrine cells), were demonstrated by double immunostaining and found to be restricted to the oxyntic mucosa. Histamine containing cells that did not stain with chromogranin A-antibodies were numerous throughout the stomach. Of the histamine immunoreactive cells in the oxyntic gland area 22% reacted with antibodies against chromogranin A. Histamine containing endocrine cells constituted 44% of the total number of endocrine cells in the oxyntic mucosa. These findings suggest that the histamine containing endocrine cells in the human stomach are identical with the so called enterochromaffin like cells.
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Affiliation(s)
- H Lönroth
- Department of Surgery, Sahlgren's Hospital, University of Gothenburg, Sweden
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Yanagisawa K, Yang H, Walsh JH, Taché Y. Role of acetylcholine, histamine and gastrin in the acid response to intracisternal injection of TRH analog, RX 77368, in the rat. REGULATORY PEPTIDES 1990; 27:161-70. [PMID: 2109337 DOI: 10.1016/0167-0115(90)90036-v] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The role of gastrin, acetylcholine and histamine in the acid response to central vagal activation induced by intracisternal injection of the stable analog, RX 77368, was further investigated in urethane-anesthetized rats with gastric fistula. The gastrin monoclonal antibody 28-2 injected intravenously, at a dose previously shown to prevent gastrin-induced stimulation of acid secretion, did not alter the peak acid response to intracisternal injection of RX 77368 (15 ng). The TRH analog (30 ng) injected into the cisterna magna increased levels of histamine measured in the hepatic portal blood. Cimetidine administered at a dose which completely blocked the stimulation of gastric acid secretion produced by intravenous infusion of histamine, inhibited by 62% the stimulatory effect of intracisternal RX 77368 (30 ng). The M1 muscarinic antagonist, pirenzepine, completely prevented the acid secretion induced by intracisternal RX 77368 (30 ng). These results indicate that the acid response to central vagal activation by the TRH analog in rats involved M1 muscarinic receptors along with histamine release acting on H2 histaminergic receptors whereas gastrin does not appear to play an important role.
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Affiliation(s)
- K Yanagisawa
- Center for Ulcer Research and Education, Veterans' Administration Medical Center, Los Angeles, CA 90073
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Cattan D, Roucayrol AM, Launay JM, Callebert J, Charasz N, Nurit Y, Belaiche J, Kalifat R. Circulating gastrin, endocrine cells, histamine content, and histidine decarboxylase activity in atrophic gastritis. Gastroenterology 1989; 97:586-96. [PMID: 2753321 DOI: 10.1016/0016-5085(89)90628-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Thirty-five patients with fundic atrophic gastritis and achlorhydria were classified in two groups according to the presence or absence of fundic argyrophil, mostly enterochromaffinlike cell hyperplasia. Among the biologic and histologic parameters studied, the hyperplasic group differed only by a circulating hypergastrinemia and an antral G-cell hyperplasia. The histamine content, the histidine decarboxylase activity, and the mast cell number of fundic biopsies were determined in 10 controls, 16 of the preceding patients (11 with and 5 without fundic argyrophil-cell hyperplasia), and 5 patients with fundic atrophic gastritis and neither achlorhydria nor hyperplasia. Histamine content and histidine decarboxylase activity were increased only in the hyperplasic group despite an unchanged mast cell number. For all fundic biopsies the argyrophil-cell density was positively related to the histamine content. Finally, the argyrophil-cell hyperplasia occurring in fundic atrophic gastritis with achlorhydria is associated not with the gastritis intensity, as assessed by histologic and secretory criteria, but with a circulating hypergastrinemia and an increase of both fundic histamine content and histidine decarboxylase activity.
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Affiliation(s)
- D Cattan
- Service de Médecine Générale et Hépato-Gastro-Entérologie, Faculté de Médecine de Créteil, France
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Fargeas MJ, Fioramonti J, Bueno L. Involvement of different receptors in the central and peripheral effects of histamine on intestinal motility in the rat. J Pharm Pharmacol 1989; 41:534-40. [PMID: 2571697 DOI: 10.1111/j.2042-7158.1989.tb06521.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The effects of histamine on intestinal motility have been investigated in conscious rats, fed or fasted, using an electromyographic method. Histamine peripherally administered (10 mg kg-1) in 15 h fasted rats induced an inhibition followed by a period of irregular spiking activity disrupting the duodenojejunal migrating myoelectric complexes (MMC) and suppressed the postprandial motor spiking activity when administered 50 min after a meal. The selective agonist of the H1-receptors, 2-pyridylethylamine (2-PEA) induced an irregular spiking activity while dimaprit acting on H2-receptors, inhibited the MMC pattern. Effects of peripherally administered histamine were antagonized by previous administration of chlorpheniramine (0.5 mg kg-1 i.p.) and in a lesser extent by cimetidine (10 mg kg-1 i.p.). Histamine (1-10 micrograms) administered intracerebroventricularly (i.c.v.) in fasted rats increased the motor cycle frequency and immediately restored the MMC pattern when given to fed rats. Among the three agonists of the H1- H2- and H3-receptors (2-PEA, dimaprit and R-alpha-methylhistamine, respectively) only R-alpha-methylhistamine (1-10 micrograms i.c.v.) was able to reproduce this effect. It is concluded that the effects of histamine on intestinal motility were centrally and peripherally mediated involving mainly H1-receptors at the peripheral level and H3-receptors at the CNS level.
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Affiliation(s)
- M J Fargeas
- Department of Pharmacology, INRA, Toulouse, France
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Gespach C, Fagot D, Emami S. Pharmacological control of the human gastric histamine H2 receptor by famotidine: comparison with H1, H2 and H3 receptor agonists and antagonists. Eur J Clin Invest 1989; 19:1-10. [PMID: 2567239 DOI: 10.1111/j.1365-2362.1989.tb00188.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Histamine 0.1 microM-0.1 mM increased adenylate cyclase activity five- to ten-fold in human fundic membranes, with a potency Ka = 3 microM. The histamine dose-response curve was mimicked by the H3 receptor agonist (R) alpha-MeHA, but at 100 times lower potency, Ka = 0.3 mM. Histamine-induced adenylate cyclase activation was abolished by H2, H1 and H3 receptor antagonists, according to the following order of potency IC50: famotidine (0.3 microM) greater than triprolidine (0.1 mM) thioperamide (2 mM), respectively. Famotidine has no action on membrane components activating the adenylate cyclase system, including the Gs subunit of the enzyme stimulated by forskolin and cell surface receptors sensitive to isoproterenol (beta 2-type), PGE2 and VIP. The Schild plot was linear for famotidine (P less than 0.01) with a regression coefficient r = 0.678. The slope of the regression line was 0.64 and differs from unity. Accordingly, famotidine showed a slow onset of inhibition and dissociation from the H2 receptor in human cancerous HGT-1 cells. The results demonstrate that famotidine is a potent and selective H2 receptor antagonist with uncompetitive actions in human gastric mucosa. Consequently, famotidine might be a suitable drug with long-lasting actions in the treatment of Zollinger-Ellison syndrome. The results also confirm and extend the previous observations that (R) alpha-MeHA and thioperamide are two selective ligands at histamine H3 receptor sites. In the human gastric mucosa, these drugs are respectively 330 and 6700 times less potent than histamine and famotidine on the adenylate cyclase system. The possible involvement of histamine H3 receptors in the regulation of gastric secretion is proposed.
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Affiliation(s)
- C Gespach
- INSERM U 55, Hôpital Saint-Antoine, Paris, France
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50
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Panula P, Pirvola U, Auvinen S, Airaksinen MS. Histamine-immunoreactive nerve fibers in the rat brain. Neuroscience 1989; 28:585-610. [PMID: 2710333 DOI: 10.1016/0306-4522(89)90007-9] [Citation(s) in RCA: 473] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
A new immunohistochemical method that utilizes carbodiimide as a tissue fixative was applied to study the distribution of histamine-immunoreactive neuronal fibers and terminals in the rat brain. Immunoreactive fibers were observed in almost all major regions of the brain. They were most numerous in the different hypothalamic nuclei. Dense networks of immunoreactive fibers were also seen in the medial septum, nucleus of the diagonal band and ventral tegmental area. A moderate density of fibers was seen throughout the cerebral cortex, in some parts of the olfactory bulb and tubercle, bed nucleus of the stria terminalis, amygdala, basal parts of the hippocampus, inferior and superior colliculi, substantia nigra, lateral and medial parabrachial nucleus, and the nucleus of the solitary tract. Few histamine-immunoreactive fibers were seen in most parts of the caudate putamen, most thalamic nuclei, most pontine and ventral medullary nuclei. Histamine-immunoreactive neuronal cell bodies were found exclusively in the tuberomammillary nucleus, in agreement with previous reports. The results provide evidence for a widespread distribution of histamine-containing nerve fibers and terminals in the rat brain. Although immunohistochemical localization of histamine does not give direct evidence of a functional role of histamine in any brain area, this distribution suggests involvement in functions of the limbic system including the septal nuclei, hypothalamus and amygdala. The relatively dense histamine-immunoreactive fiber networks in the colliculi and dorsal cochlear nucleus indicate that this amine may play a role in visual functions and hearing. The paucity of immunoreactive fibers in the pontine and medullary areas suggests that the caudal projections originating from the tuberomammillary complex are minor ones compared to the major rostral projections. Several fiber projections originating from the tuberomammillary complex could be deduced from serial frontal, sagittal and horizontal sections. They contained fibers that crossed the midline at several levels of the brain. The results provide information on the target areas of the histaminergic neurons and form a basis for the examination of cellular contracts between the histaminergic neurons and other cells.
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Affiliation(s)
- P Panula
- Department of Anatomy, University of Helsinki, Finland
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