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Khajeh F, Safari F, Seyyedi N, Asadian F, Farhadi A, Behzad-Behbahani A. Gastric Perforation in a 60-Year-Old Woman with CMV Gastritis and Amphetamine Abuse Led to Death. Case Rep Gastroenterol 2022; 16:129-134. [PMID: 35528772 PMCID: PMC9035922 DOI: 10.1159/000521719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 12/17/2021] [Indexed: 11/28/2022] Open
Abstract
Gastric perforation as a multi-etiological disease is a full-thickness injury of the stomach wall. In this case report, we presented a 60-year-old woman with a history of suicidal behavior referred to the emergency unit with a decreased level of consciousness due to the multidrug consumption (amphetamine and benzodiazepine). Passing 3 days of admission in the intensive care unit, the patient represented severe abdominal distension, lack of defecation, and the absence of bowel sound, which suggested the gastrointestinal (GI) complication. Abdominal-pelvic sonography followed by laparotomy confirmed the gastric perforation, which finally led to the patient's death. Pathological analysis showed that the vast involvement of cytomegalovirus (CMV) in the patient's GI tract resulted in several peptic ulcers. The first report of gastric perforation-related death arises from the partnership of CMV infection and drug poisoning.
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Affiliation(s)
- Fatemeh Khajeh
- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
- Fasa University of Medical Sciences, Fasa, Iran
| | - Fatemeh Safari
- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Noorossadat Seyyedi
- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Asadian
- Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Farhadi
- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abbas Behzad-Behbahani
- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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de Oliveira DMN, Oliveira-Silva CA, Pinheiro CG, de Carvalho EF, Gadelha KKL, Lima-Silva K, Cavalcante AKM, Belém MDO, Paula SM, Dos Santos AA, Magalhães PJC. Differential effects of β-methylphenylethylamine and octopamine on contractile parameters of the rat gastrointestinal tract. Eur J Pharmacol 2021; 908:174339. [PMID: 34265293 DOI: 10.1016/j.ejphar.2021.174339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 06/15/2021] [Accepted: 07/11/2021] [Indexed: 11/27/2022]
Abstract
This study tested the effects of β-methylphenylethylamine (β-MPEA) and octopamine on contractile parameters of the gastrointestinal tract in rats. We hypothesized that some of their effects result from interactions with trace amine (TA)-associated receptors or serotoninergic 5-hydroxytryptamine (5-HT) receptors. β-MPEA-induced contractions in rat gastric fundus strips under resting tonus conditions, but induced relaxation in preparations that were previously contracted with carbachol. Octopamine relaxed gastric fundus strips maintained at resting tonus or contracted with carbachol. The contractile effect of β-MPEA was reduced by cyproheptadine and methiothepin, antagonists of excitatory 5-HT receptors. The relaxing effect of β-MPEA on gastric fundus was insensitive to pretreatment with N-(3-ethoxyphenyl)-4-(1-pyrrolidinyl)-3-(trifluoromethyl)benzamide (EPPTB) and tropisetron, antagonists of TA1 and 5-HT4 receptors, respectively. Both EPPTB and tropisetron inhibited the relaxant effects of octopamine on carbachol-contracted preparations. Contrarily, EPPTB did not reduce the relaxant effects of RO5263397 (TA1 agonist) or zacopride (5-HT4 agonist). Octopamine, but not β-MPEA, delayed the gastrointestinal transit of a liquid test meal in awaken rats. In isolated preparations of the small intestine under resting conditions, β-MPEA did not alter the basal tonus, but octopamine relaxed it. Intestinal preparations previously contracted with carbachol relaxed after the addition of octopamine and decreased the magnitude of their spontaneous rhythmic contractions in a tropisetron-dependent manner. Thus, β-MPEA and octopamine exerted pharmacological actions on the rat gastrointestinal tract. The excitatory effects of β-MPEA involved 5-HT receptors. Octopamine inhibited the rat gut contractility through the likely involvement of 5-HT4 and TA receptors. Overall, octopamine effectively inhibited rat gastrointestinal transit.
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Affiliation(s)
| | | | - Camila Gadelha Pinheiro
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | | | - Kalinne Kelly Lima Gadelha
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Karine Lima-Silva
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | | | - Mônica de Oliveira Belém
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Suliana Mesquita Paula
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Armênio Aguiar Dos Santos
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Pedro Jorge Caldas Magalhães
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
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Yu HZ, Fu MH, Ji XP, E-Ni RG. Progress in research of gastrointestinal motility regulation. Shijie Huaren Xiaohua Zazhi 2020; 28:1183-1191. [DOI: 10.11569/wcjd.v28.i23.1183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal motility is an important part of the physiological function of the digestive tract, and its dysfunction is one of the key factors that cause different gastrointestinal motility disorders. These diseases seriously affect patients' normal life. With the development of scientific research and technology, well-designed research studies have been conducted on the regulatory mechanisms of gastrointestinal motility, which mainly include the regulation of gastrointestinal hormones, intestinal microflora, neurotransmitters, brain-gut peptides, interstitial cells of Cajal, and gastrointestinal electrical activities. In addition, current studies have proved that bitter taste receptors have certain regulatory effects on gastrointestinal motility. This paper primarily discusses the relevant pathways controlling gastrointestinal motility.
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Affiliation(s)
- Hong-Zhen Yu
- School of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Ming-Hai Fu
- School of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Xiao-Ping Ji
- School of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Rong-Gui E-Ni
- School of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
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Ren HX, Tang QC, Yan L, Xia H, Luo HS. Evodiamine inhibits gastrointestinal motility via CCK and CCK1 receptor in water-avoidence stress rat model. Life Sci 2018; 209:210-216. [PMID: 30086275 DOI: 10.1016/j.lfs.2018.08.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 07/31/2018] [Accepted: 08/01/2018] [Indexed: 02/08/2023]
Abstract
AIM Evodiamine (EVO) has been reported to play an important role in regulating gastrointestinal motility, but the evidence is insufficient, and the mechanism remains unknown. The aim of this study is to investigate the possible role of EVO in stress-induced colonic hypermotility and the potential mechanisms via both in vivo and in vitro investigations. METHODS Male Sprague-Dawley rats were exposed to water avoidance stress (WAS) for 1 h or sham WAS daily for 10 consecutive days to construct the rat model. The colonic contractile activity was studied in an organ bath system. The serum CCK-8 level was detected using an enzyme immunoassay kit, and gastrointestinal transit was detected by intragastric administration of India ink. RESULTS WAS induced gastrointestinal hypermotility in male rats. EVO significantly inhibited the contractile activity of colonic muscle strips; this effect was not blocked by TTX and the CCK1 receptor antagonist devazepide. Chronic WAS induced a slight but nonsignificant increase in the serum CCK-8 level, while EVO elevated the serum CCK-8 level in the WAS rats in a dose-dependent manner. Exogenous CCK-8 significantly inhibited the contractile activity of the colonic muscle strips; this effect was not blocked by TTX but was completely blocked by devazepide. Both EVO and CCK-8 inhibited gastrointestinal transit, and the effect of EVO could be partially blocked by devazepide. SIGNIFICANCE EVO can reverse stress-induced gastrointestinal hypermotility. This effect may partially occur as a result of promoting the release of CCK and then activating the CCK1 receptor instead of directly activating the CCK1 receptor.
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Affiliation(s)
- H X Ren
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060, China
| | - Q C Tang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060, China
| | - L Yan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060, China
| | - H Xia
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Diseases, 430060, China
| | - H S Luo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Diseases, 430060, China.
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Huang HH, Chen LY, Doong ML, Chang SC, Chen CY. α-melanocyte stimulating hormone modulates the central acyl ghrelin-induced stimulation of feeding, gastrointestinal motility, and colonic secretion. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2377-2386. [PMID: 28860709 PMCID: PMC5566386 DOI: 10.2147/dddt.s143749] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect. Objective This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats. Methods and procedures We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters. Results ICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P<0.01), enhanced non-nutrient semi-liquid gastric emptying (P<0.001), increased the geometric center and running percentage of small intestinal transit (P<0.001), accelerated colonic transit time (P<0.05), and increased fecal pellet output (P<0.01) and total fecal weight (P<0.01). Pretreatment with ICV injection of α-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of α-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit (P<0.01). However, neither dose of α-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time. Conclusion α-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. α-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.
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Affiliation(s)
- Hsien-Hao Huang
- Institute of Clinical Medicine, National Yang-Ming University of Medicine.,Department of Emergency Medicine, Taipei Veterans General Hospital
| | - Liang-Yu Chen
- Aging and Health Research Center, National Yang-Ming University.,Center for Geriatrics and Gerontology, Taipei Veterans General Hospital
| | - Ming-Luen Doong
- Institute of Physiology, National Yang-Ming University School of Medicine
| | - Shi-Chuan Chang
- Institute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine.,Department of Chest Medicine, Taipei Veterans General Hospital
| | - Chih-Yen Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei.,Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan
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Yeh C, Ting CH, Doong ML, Chi CW, Lee SD, Chen CY. Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2016; 10:3281-3290. [PMID: 27757017 PMCID: PMC5055120 DOI: 10.2147/dddt.s113195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Purpose Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated. Methods We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln14-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV) catheters. The functional importance of corticotropin-releasing factor (CRF) receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin2-B. Results ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln14-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2 pathway. Conclusion ICV-infused urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats. Our results clearly showed that enhancing ghrelin and blocking CRF receptor 2 signaling in the brain accelerated gastric emptying, which provided important clues for a new therapeutic avenue in ameliorating anorexia and gastric ileus found in various chronic wasting disorders.
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Affiliation(s)
- Chun Yeh
- Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital
| | | | | | - Chin-Wen Chi
- Institute of Pharmacology, National Yang-Ming University School of Medicine; Department of Medical Research, Taipei Veterans General Hospital
| | - Shou-Dong Lee
- Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital
| | - Chih-Yen Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital; Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei; Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan
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Babiskin AH, Zhang X. Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation. J Pharm Sci 2015; 104:3170-82. [DOI: 10.1002/jps.24474] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 04/08/2015] [Accepted: 04/09/2015] [Indexed: 11/06/2022]
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Marks L, Beard E, Cobey D, Moore N, Motyer V, Valentin JP, Ewart L. An evaluation of the non-invasive faecal pellet assessment method as an early drug discovery screen for gastrointestinal liability. J Pharmacol Toxicol Methods 2013; 68:123-36. [DOI: 10.1016/j.vascn.2013.03.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 03/20/2013] [Accepted: 03/21/2013] [Indexed: 12/24/2022]
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Seow KM, Lee JL, Doong ML, Huang SW, Hwang JL, Huang WJ, Chang FY, Ho LT, Juan CC. Human chorionic gonadotropin regulates gastric emptying in ovariectomized rats. J Endocrinol 2013. [PMID: 23197744 DOI: 10.1530/joe-12-0421] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Prolongation of gastrointestinal transit resulting in nausea and vomiting in pregnancy (NVP) is the most common phenomenon during the first trimester of pregnancy. Increased human chorionic gonadotropin (hCG) concentration during the first trimester is the most likely cause of NVP. The aim of this study was to investigate the effect of hCG on gastrointestinal transit and plasma concentrations of cholecystokinin (CCK) in ovariectomized (Ovx) rats. I.p. injection of hCG was used to evaluate the dose effect of hCG on gastrointestinal transit in Ovx rats. The CCK antagonist lorglumide was used to clarify the role of CCK in regulating gastrointestinal transit. Gastrointestinal transit was assessed 15 min after intragastric gavage of a mixture of 10% charcoal and Na(2)(51)CrO(4) (0.5 μCi/ml). After i.p. administration of hCG, gastric emptying was inhibited in Ovx rats, but intestinal transit was not affected. Plasma CCK concentrations were increased in a dose-dependent manner after hCG treatment, and gastric emptying showed a significant negative correlation with CCK concentrations (P=0.01, r(2)=-0.5104). Peripheral administration (i.p.) of lorglumide, a selective CCK(1) receptor antagonist, attenuated the hCG-induced inhibition of gastric emptying in Ovx rats, whereas central administration via the i.c.v. route did not. hCG treatment of Ovx rats inhibits gastric emptying in a dose-dependent manner via a peripheral mechanism of CCK hypersecretion and activation of CCK(1) receptors.
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Affiliation(s)
- Kok-Min Seow
- Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Chang FY, Lu CL, Chen TS, Wang PS. The role of cholecystokinin 1 receptor in prolactin inhibited gastric emptying of male rat. J Neurogastroenterol Motil 2012; 18:385-90. [PMID: 23105998 PMCID: PMC3479251 DOI: 10.5056/jnm.2012.18.4.385] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2012] [Revised: 06/14/2012] [Accepted: 06/19/2012] [Indexed: 11/24/2022] Open
Abstract
Background/Aims Prolactin (PRL) is essential for the lactating mammals, while cholecystokinin (CCK) does inhibit gastric emptying (GE). Present study attempted to determine whether both peptides interacted on the male rat GE, particularly the role of putative CCK1 receptor. Methods Acute hyperprolactinemia of male rats was induced by the intraperitoneal injection of ovine PRL (oPRL) in several divided doses 15 minutes before motility study. Rat chronic hyperprolactinemia was induced by the graft of 2 pituitary glands into the capsule of left kidney, while control rats received cerebral cortex graft only. Motility study was conducted 6 weeks later after graft surgery. Fifteen minutes after the intragastric feeding of radiochromium, rat was sacrificed to measure GE via the distribution of radioactivities within stomach and intestine. Among the CCK1 receptor blocking study using lorglumide, rats were divided to receive the regimens in terms of oPRL-vehicle plus lorglumide-vehicle, oPRL plus lorglumide-vehicle, oPRL-vehicle plus lorglumide and oPRL plus lorglumide. Plasma CCK level was measured using a homemade radioimmunoassay kit. Results Compared to vehicle treatment, acute hyperprolactinemic rats under highest dose (2.0 mg/kg) of oPRL treatment showed delayed GE (70.6% ± 3.0% vs 42.1% ± 6.6%, P < 0.05). Chronic hyperprolactinemic rats under graft surgery also showed inhibited GE (70.5% ± 1.7% vs 54.5% ± 4.7%, P < 0.05). Both models finally obtained elevated plasma CCK levels (P < 0.05). Lorglumide itself did not influence GE, however, delayed GE under oPRL treatment was restored following the concomitant lorglumide treatment. Conclusions Our study suggests that PRL may delay male rat GE via a mechanism of endogenous CCK activation involving the peripheral CCK1 receptor.
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Affiliation(s)
- Full-Young Chang
- Environmental Heath and Safety Office and Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan
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Natale G, Kastsiuchenka O, Pasquali L, Ruggieri S, Paparelli A, Fornai F. MPTP- but Not Methamphetamine-Induced Parkinsonism Extends to Catecholamine Neurons in the Gut. Ann N Y Acad Sci 2008; 1139:345-9. [DOI: 10.1196/annals.1432.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Chittrakarn S, Sawangjaroen K, Prasettho S, Janchawee B, Keawpradub N. Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract. JOURNAL OF ETHNOPHARMACOLOGY 2008; 116:173-178. [PMID: 18191353 DOI: 10.1016/j.jep.2007.11.032] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2006] [Revised: 11/11/2007] [Accepted: 11/15/2007] [Indexed: 05/25/2023]
Abstract
Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Thailand used traditionally in folk medicine although it is claimed to cause addiction. It is used to treat diarrhea, however, there is no scientific evidence to support the use. The aim of this study is to investigate the effect of methanolic extract of kratom leaves on the rat gastrointestinal tract. Kratom extract at 50, 100, 200 and 400 mg/kg (p.o.) caused a dose dependent protection against castor oil-induced diarrhea in rats and also inhibited intestinal transit. The antidiarrheal effect was not antagonized by naloxzone. The inhibition of intestinal transit by kratom extract was significantly different from the control when treated with a single dose for 1 day. For longer-term treatments of 15 and 30 days, kratom extract did not decrease the intestinal transit time indicating that adaptation had occurred. Kratom extract at a dose level of 200 and 400 mg/kg for 30 days and morphine at 3 mg/kg (i.p.) caused a decrease in the increment of body weight that was significantly different from the control and kratom extract at lower doses (50 and 100 mg/kg). However it had no effect on the level of plasma cholecystokinin. The results suggested that methanolic kratom extract exhibited its antidiarrheal effect on rat gastrointestinal tract. The effects may occur via pathways in addition to the action on opioid receptors. High does of kratom extract decreased the increment of body weight similar to the effect of morphine.
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Affiliation(s)
- Somsmorn Chittrakarn
- Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand.
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Wu CL, Doong ML, Wang PS. Involvement of cholecystokinin receptor in the inhibition of gastrointestinal motility by oxytocin in ovariectomized rats. Eur J Pharmacol 2007; 580:407-15. [PMID: 18078924 DOI: 10.1016/j.ejphar.2007.11.024] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2007] [Revised: 10/29/2007] [Accepted: 11/10/2007] [Indexed: 01/04/2023]
Abstract
The effects of oxytocin on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in ovariectomized rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2 51CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of oxytocin (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK1 receptor antagonists, devazepide and lorglumide, effectively attenuated the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK2 receptor antagonist, did not alter the oxytocin-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that oxytocin inhibits gastric emptying and gastrointestinal transit in ovariectomized rats via a mechanism involving the stimulation of CCK release and CCK1 receptor activation.
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Affiliation(s)
- Chiu-Lung Wu
- Department of Basic Medical Science, Hung-Kuang University, Taiwan, ROC.
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Alvarez A, Ibiza S, Hernández C, Alvarez-Barrientos A, Esplugues JV, Calatayud S. Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori. FASEB J 2006; 20:2396-8. [PMID: 17015411 DOI: 10.1096/fj.05-5696fje] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Gastric mucosal inflammation causes hypergastrinemia, and gastrin receptors have been detected in several leukocyte types. We have analyzed whether gastrin affects the leukocyte-endothelial cell interactions in vivo by monitoring leukocyte rolling, adhesion, and emigration in rat mesenteric venules using intravital microscopy. Mesenteric superfusion with exogenous gastrin increased these processes in a concentration- and time-dependent manner, effects prevented by the cholecystokinin (CCK)-2 receptor antagonists (proglumide, L-365,260) but not by the CCK-1 receptor antagonist devazepide. A similar response was induced by exogenous CCK or endogenously released gastrin. CCK-2 receptors were localized in mesenteric macrophages and polymorphonuclear leukocytes. This effect of gastrin is not modulated by somatostatin and is independent of the endogenous release of histamine. To analyze whether hypergastrinemia elicited by Helicobacter pylori (HP) modulates the inflammation induced by the germ, rats were chronically administered with an extract of a CagA+/VacA+ strain of HP. This protocol increased gastrinemia and induced an inflammatory response in the rat mesentery. Blockade of CCK-2 receptors attenuated this response and induced a qualitative change in the leukocyte infiltrate suggestive of a receding inflammatory process. Our results reveal a new proinflammatory role of gastrin that seems to contribute to the maintenance of the inflammation elicited by HP components.
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Affiliation(s)
- Angeles Alvarez
- Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Avd. Blasco Ibáñez 15, 46010-Valencia, Spain
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Izbéki F, Wittmann T, Csáti S, Lonovics J. The mechanisms of the inhibitory effect of ethanol on gastric emptying involve type A CCK receptors. REGULATORY PEPTIDES 2004; 117:101-105. [PMID: 14700745 DOI: 10.1016/j.regpep.2003.09.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The mechanisms involved in the mediation of the inhibitory effects of ethanol on gastric emptying were studied in adult male rats. The gastric emptying was determined by measuring the amount of phenol red recovered from the stomach after intragastric administration. Intragastric administration of a 2.5 g kg(-1) body weight dose of ethanol resulted in inhibition of the gastric emptying. Prior intraperitoneal treatment with lorglumide (CR-1409), a selective CCK-A receptor antagonist, abolished the inhibitory effect of ethanol on the gastric emptying. This observation furnishes evidence indicative of the involvement of type A CCK receptors in the mediation of the inhibitory effect of large doses of ethanol on the gastric emptying.
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Affiliation(s)
- Ferenc Izbéki
- 1st Department of Internal Medicine, University of Szeged, Korányi fasor 8, H-6720 Szeged, Hungary.
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Wu CL, Hung CR, Chang FY, Pau KYF, Wang PS. Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2003; 367:406-13. [PMID: 12690433 DOI: 10.1007/s00210-003-0690-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2002] [Accepted: 01/03/2003] [Indexed: 10/25/2022]
Abstract
The effects of oxytocin (OT) on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in female rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)(51)CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of OT (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT- induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the OT-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK(2) receptor antagonist, did not alter the OT-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that OT inhibits gastric emptying and gastrointestinal transit in female rats via a mechanism involving CCK stimulation and CCK(1) receptor activation.
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Affiliation(s)
- Chiu-Lung Wu
- Department of Physiology, School of Medicine, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan, Republic of China
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Wu CL, Hung CR, Chang FY, Lin LC, Pau KYF, Wang PS. Effects of evodiamine on gastrointestinal motility in male rats. Eur J Pharmacol 2002; 457:169-76. [PMID: 12464363 DOI: 10.1016/s0014-2999(02)02687-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The effects of evodiamine on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in male rats. Evodiamine, isolated from the dry unripened fruit of Evodia rutaecarpa Bentham (a Chinese medicine named Wu-chu-yu), has been recommended for abdominal pain, acid regurgitation, nausea, diarrhea, and dysmenorrhea. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)51CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay (RIA). After administration of evodiamine (0.67-6.00 mg/kg), both gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. L-365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl)-N'-(3-methylphenyl)-urea), a selective CCK(2) receptor antagonist, did not alter the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that evodiamine inhibits both gastric emptying and gastrointestinal transit in male rats via a mechanism involving CCK release and CCK(1) receptor activation.
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Affiliation(s)
- Chiu-Lung Wu
- Department of Physiology, School of Medicine, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan, ROC
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18
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Liu CY, Chen LB, Liu PY, Xie DP, Wang PS. Effects of progesterone on gastric emptying and intestinal transit in male rats. World J Gastroenterol 2002; 8:338-41. [PMID: 11925620 PMCID: PMC4658379 DOI: 10.3748/wjg.v8.i2.338] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility.
METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 mL/kg) containing Na251CrO4 (0.5 μCi/mL) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol.
RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75% ± 3%, P < 0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42% ± 11.2%, P < 0.01). P (1 mg/kg) increased the intestinal transit (4.2 ± 0.3, P < 0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5% ± 9.8%, P < 0.01). The inhibitory effects of P (20 mg/kg) (32% ± 9.7%, P < 0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17% ± 9.4%, P < 0.01).
CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.
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Affiliation(s)
- Chuan-Yong Liu
- Department of Physiology, School of Medicine, Shandong University, Jinan 250012, Shandong Province, China.
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Thomson AB, Keelan M, Thiesen A, Clandinin MT, Ropeleski M, Wild GE. Small bowel review: normal physiology part 2. Dig Dis Sci 2001; 46:2588-607. [PMID: 11768248 DOI: 10.1023/a:1012746622735] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) numerous peptides are being identified which stimulate the proliferation and functional response of the small intestine to disease or resection, and may in time find a clinical use; (2) under usual in vivo conditions, absorption of nutrients has little effect on the paracellular movement of water; (3) the permeability of the intestine is modified by the function of the tight junctions, and measuring intestinal permeability may be useful to reflect the presence of disease; (4) the release of serotonin is influenced by cholinergic, adrenergic, and nonadrenergic, noncholinergic mechanisms, and serotonin agonists and antagonists may play an important future role in the treatment of motility disorders; (5) the use of endothelin receptor antagonists may be useful for the treatment of intestinal anaphylaxis; (6) the alterations in intestinal pH and motility in patients with Crohn's disease may influence the action of pH- or time-dependent release medications; and (7) patients with irritable bowel syndrome may also have abnormalities in gastric and small intestinal motility.
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Affiliation(s)
- A B Thomson
- Department of Medicine, University of Alberta, Edmonton, Canada
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Chang FY, Doong ML, Chen TS, Lee SD, Wang PS. Vasoactive intestinal polypeptide appears to be one of the mediators in misoprostol-enhanced small intestinal transit in rats. J Gastroenterol Hepatol 2000; 15:1120-4. [PMID: 11106090 DOI: 10.1046/j.1440-1746.2000.02306.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Prostaglandin analogs have the pharmacologic effect of speeding up small intestinal transit (SIT). It remains unknown whether some gut peptides also mediate this enhancement. We studied the effect of misoprostol on rat SIT and looked at the role of vasoactive intestinal polypeptide (VIP) release during its action. METHODS A group of rats initially received oral misoprostol treatment of 1, 10, 50 and 100 microg/kg, respectively. By using orally fed charcoal as a motility marker, the SIT was assessed at 30 min following oral misoprostol treatment. Another group of rats received misoprostol as an intraperitoneal injection in similar doses to the group above. The small intestinal transit was computed for this group at 30 min following misoprostol injection via an instilled radiochromium motility marker that went through a previously placed intraduodenal catheter. The plasma VIP level was measured by using a radioimmunoassay kit. RESULTS Neither charcoal evaluated transit nor the plasma VIP level was influenced by the lower doses of oral misoprostol treatment (1 and 10 microg/kg), whereas other doses enhanced SIT and diminished the plasma VIP level (P< 0.01).The similar effects on radiochromium computed SIT (P< 0.01) and plasma VIP levels were obtained in tubed rats following misoprostol intraperitoneal treatment. The SIT results correlated negatively with plasma VIP levels. CONCLUSIONS Enhanced SIT and diminished VIP levels are found in rats following misoprostol treatment. It appears that inhibited VIP release is one of the mechanisms in misoprostol-enhanced SIT.
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Affiliation(s)
- F Y Chang
- Division of Gastroenterology, Taipei Veterans General Hospital, National Yang-Ming University, Taiwan.
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Quigley EM. Gastroduodenal motility. Curr Opin Gastroenterol 1999; 15:481-91. [PMID: 17023994 DOI: 10.1097/00001574-199911000-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Several major themes emerged over the past year in the area of gastroduodenal motility. Mostly, these themes represented extensions of research areas discussed in prior reviews in this series rather than the emergence of completely new concepts. Thus, for example, considerable emphasis has again been placed on regional gastric motor function in dyspepsia and on the role of fundic relaxation and accommodation, in particular. Not surprisingly, basic physiologic research has also shown a keen interest in the regulation of fundic relaxation. One new and exciting development is the recognition of the stomach's role in satiety. The spectrum of gastric motor dysfunction in diabetes mellitus continues to be explored, and the important role of hyperglycemia in regulating gastric function has been further emphasized. More data have been provided on noninvasive alternatives to gastric motor function testing, and several studies have looked at factors that may influence variability in these various tests. There have been few innovations over the past year in the therapeutic arena; rather, the indications and limitations of current therapies have been further developed.
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Affiliation(s)
- E M Quigley
- Department of Medicine, National University of Ireland, Cork, Ireland.
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