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Ma XZ, Zhou N, Luo X, Guo SQ, Mai P. Update understanding on diagnosis and histopathological examination of atrophic gastritis: A review. World J Gastrointest Oncol 2024; 16:4080-4091. [DOI: 10.4251/wjgo.v16.i10.4080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a complex syndrome in which long-term chronic inflammatory stimulation causes gland atrophy in the gastric mucosa, reducing the stomach's ability to secrete gastric juice and pepsin, and interfering with its normal physiological function. Multiple pathogenic factors contribute to CAG incidence, the most common being Helicobacter pylori infection and the immune reactions resulting from gastric autoimmunity. Furthermore, CAG has a broad spectrum of clinical manifestations, including gastroenterology and extra-intestinal symptoms and signs, such as hematology, neurology, and oncology. Therefore, the initial CAG evaluation should involve the examination of clinical and serological indicators, as well as diagnosis confirmation via gastroscopy and histopathology if necessary. Depending on the severity and scope of atrophy affecting the gastric mucosa, a histologic staging system (Operative Link for Gastritis Assessment or Operative Link on Gastritis intestinal metaplasia) could also be employed. Moreover, chronic gastritis has a higher risk of progressing to gastric cancer (GC). In this regard, early diagnosis, treatment, and regular testing could reduce the risk of GC in CAG patients. However, the optimal interval for endoscopic monitoring in CAG patients remains uncertain, and it should ideally be tailored based on individual risk evaluations and shared decision-making processes. Although there have been many reports on CAG, the precise etiology and histopathological features of the disease, as well as the diagnosis of CAG patients, are yet to be fully elucidated. Consequently, this review offers a detailed account of CAG, including its key clinical aspects, aiming to enhance the overall understanding of the disease.
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Affiliation(s)
- Xiu-Zhen Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| | - Ni Zhou
- Department of Gastroenterology, Xi'an International Medical Center, Xi’an 710000, Shaanxi Province, China
| | - Xiu Luo
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Si-Qi Guo
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
- The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Ping Mai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
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Otsuka M, Huang J, Tanaka T, Sakata I. Identification of glucagon like peptide-1 (GLP-1) in mice stomach. Biochem Biophys Res Commun 2024; 704:149708. [PMID: 38417346 DOI: 10.1016/j.bbrc.2024.149708] [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: 02/08/2024] [Revised: 02/18/2024] [Accepted: 02/20/2024] [Indexed: 03/01/2024]
Abstract
Glucagon like peptide-1 (GLP-1) is a peptide hormone encoded by the pre-proglucagon gene that serves multiple physiological functions, including incretin action. While GLP-1 is primarily synthesized in the L cells of the lower intestine, recent findings indicate its presence in the stomachs of both rats and humans. However, the role of gastric GLP-1 in other species remains unclear. In this study, we aimed to identify GLP-1-producing cells and examine the localization of GLP-1 production in the mouse stomach. We found that pre-proglucagon mRNA was higher in the corpus than that in the antrum of the stomach. In addition, GLP-1 immunoreactive cells were found in the gastric mucosa, and their cell number was higher in the corpus than that in the antrum. Double immunofluorescence showed that some GLP-1 immunoreactive cells displayed somatostatin immunoreactivity, whereas did not co-localize with ghrelin and gastrin. Moreover, transmembrane G protein-coupled Receptor 5 (TGR5) agonist decreased pre-proglucagon mRNA expression in SG-1 cells in a concentration-dependent manner, and in vivo experiments showed a decrease in its mRNA levels in the gastric corpus but not in the antrum. This study marks the first report of GLP-1 production in the mouse stomach. Our findings suggest that gastric pre-proglucagon mRNA expression is regulated by a distinct mechanism compared to the L cells of the lower intestine.
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Affiliation(s)
- Manami Otsuka
- Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama, 338-8570, Japan
| | - Jin Huang
- Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama, 338-8570, Japan
| | - Toru Tanaka
- Faculty of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Josai University, Saitama, 1-1 Keiyaki dai, Sakado, Saitama, 350-0295, Japan
| | - Ichiro Sakata
- Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama, 338-8570, Japan; Area of Research Evolutionary Molecular Design, Strategic Research Center, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama, 338-8570, Japan.
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Matsumoto M, Takemi S, Sakai T, Sakata I. Identification of motilin in Japanese fire bellied newt. Gen Comp Endocrinol 2022; 323-324:114031. [PMID: 35331740 DOI: 10.1016/j.ygcen.2022.114031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/17/2022] [Accepted: 03/19/2022] [Indexed: 11/30/2022]
Abstract
Motilin, a peptide hormone consisting of 22 amino acid residues, was identified in the duodenum of pigs in the 1970s. It is known to induce gastrointestinal contractions during the interdigestive state in mammals. Although the motilin gene has been identified in various animal species, it has not been studied in amphibians. Here, we identified the motilin gene in the Japanese fire bellied newt (Cynops pyrrhogaster), and conducted an analysis of tissue distribution, morphological observations, and physiological experiments. The deduced mature newt motilin comprises 22 amino acid residues, like in mammals and birds. The C-terminus of the newt motilin showed high homology with motilin from other species compared to the N-terminus region, which is considered the bioactive site. Motilin mRNA expression in newts was abundant in the upper small intestine, with notably high motilin mRNA expression found in the pancreas. Motilin-producing cells were found in the mucosal layer of the upper small intestine and existed as two cell types: open-and closed-type cells. Motilin-producing cells in the pancreas were also found to produce insulin but not glucagon. Newt motilin stimulated gastric contractions but not in other parts of the intestines in vitro, and motilin-induced gastric contraction was significantly inhibited by treatment with atropine, a muscarinic acetylcholine receptor antagonist. These results indicate that motilin is also present in amphibians, and that its gastrointestinal contractile effects are conserved in mammals, birds, and amphibians. Additionally, we demonstrated for the first time the existence of pancreatic motilin, suggesting that newt motilin has an additional unknown physiological role.
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Affiliation(s)
- Mio Matsumoto
- Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan
| | - Shota Takemi
- Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan
| | - Takafumi Sakai
- Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan
| | - Ichiro Sakata
- Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan; Area of Life-NanoBio, Division of Strategy Research, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan.
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Serra-Campos AO, Abreu-Junior ANG, Nascimento AA, Abidu-Figueiredo M, Lima MSCS, Machado-Santos C. Gastroesophageal tube of the Iguana iguana (Iguanidae): histological description, histochemical and immunohistochemical analysis of 5-HT and SS cells. BRAZ J BIOL 2021; 83:e242086. [PMID: 34161453 DOI: 10.1590/1519-6984.242086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 01/12/2021] [Indexed: 11/21/2022] Open
Abstract
The work aims were to describe the histological and histochemical structure of the gastroesophageal tube of Iguana iguana and verify the occurrence and distribution of immunoreactive serotonin (5-HT) and somatostatin (SS) cells. Fragments of the gastrointestinal tract (GIT) of five iguanas were which underwent standard histological and immunohistochemistry technique. Immunoreactive cells for 5-HT and SS were quantified using the STEPanizer. The oesophagus has ciliated columnar pseudostratified epithelium with staining Alcian blue (AB) + and goblet cells highly reactive to periodic acid Schiff (PAS). In the cervical oesophagus, the numerical density of 5-HT cells per unit area (QA [5-HT cells]/µm2) was 4.6x10-2 ± 2.0 and celomatic oesophagus presented QA = 4.0x10-2 ± 1.0. The epithelium of the stomach is simple columnar, PAS and AB +. The cranial and middle regions of the stomach presented (QA [5-HT cells]/µm2) = 6.18x10-2 ± 3.2 and the caudal region, QA = 0.6x10-2 ± 0.2. The SS cells were only observed in the caudal stomach, with numerical density (QA [SS cells]/µm2) = 1.4x10-2 ± 0.9 In I. iguana, variation was observed in terms of the distribution of mucus secretions and the pattern of occurrence of serotonin and somatostatin-secreting enteroendocrine cells in the TGI, which possibly will result in an interspecific adaptive response.
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Affiliation(s)
- A O Serra-Campos
- Universidade Federal Fluminense - UFF, Departamento de Morfologia, Laboratório de Ensino e Pesquisa em Histologia e Embriologia Comparada - LEPHEC, Niterói, RJ, Brasil
| | - A N G Abreu-Junior
- Universidade Federal do Piauí - UFPI, Departamento de Biologia, Laboratório de Herpertologia, Floriano, PI, Brasil
| | - A A Nascimento
- Universidade Federal Rural do Rio de Janeiro - UFRRJ, Instituto de Ciências Biológicas e da Saúde, Programa de Pós-graduação em Biologia Animal, Seropédica, RJ, Brasil
| | - M Abidu-Figueiredo
- Universidade Federal Rural do Rio de Janeiro - UFRRJ, Instituto de Ciências Biológicas e da Saúde, Programa de Pós-graduação em Biologia Animal, Seropédica, RJ, Brasil
| | - M S C S Lima
- Universidade Federal do Piauí - UFPI, Departamento de Biologia, Laboratório de Herpertologia, Floriano, PI, Brasil
| | - C Machado-Santos
- Universidade Federal Fluminense - UFF, Departamento de Morfologia, Laboratório de Ensino e Pesquisa em Histologia e Embriologia Comparada - LEPHEC, Niterói, RJ, Brasil
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Gastrin releasing peptide-induced satiety is associated with hypothalamic and brainstem changes in chicks. Neurosci Lett 2019; 713:134529. [PMID: 31585210 DOI: 10.1016/j.neulet.2019.134529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 09/24/2019] [Accepted: 09/30/2019] [Indexed: 11/23/2022]
Abstract
Gastrin releasing peptide (GRP) is involved in the stimulation of gastric acid release from the stomach. It also mediates effects on feeding behavior. It is associated with anorexigenic effects in both mammalian and avian species, but the mechanism of action is unknown in any species. The aim of the present study was thus to investigate the hypothalamic and brainstem mechanisms mediating GRP-induced satiety in chicks. In Experiment 1, chicks that received intracerebroventricular (ICV) injection of GRP reduced food intake for up to 150 min following injection and reduced water intake up to 120 min following injection. In Experiment 2, chicks that were food restricted following GRP injection did not reduce water intake. Alimentary canal transit time was not affected by GRP in Experiment 3. A behavior analysis was conducted in Experiment 4, revealing that GRP-treated chicks reduced feeding pecks. In Experiment 5, GRP-treated chicks had increased c-Fos immunoreactivity in the lateral hypothalamus, paraventricular nucleus, and arcuate nucleus of the hypothalamus, and the nucleus of the solitary tract. Collectively, these results demonstrate that central GRP causes anorexigenic effects that are associated with hypothalamic changes without affecting other behaviors.
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Tsolakis AV. Enterochromaffin-Like Cells. ENCYCLOPEDIA OF ENDOCRINE DISEASES 2019:565-570. [DOI: 10.1016/b978-0-12-801238-3.66115-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Classification of Epithelial Malignant Tumors-the Differentiation Between Adenocarcinomas and Neuroendocrine Carcinomas: Why Rely on Nonspecific Histochemistry and Dismiss Specific Methods Like Immunohistochemistry and In Situ Hybridization? Appl Immunohistochem Mol Morphol 2018; 24:309-12. [PMID: 26067134 DOI: 10.1097/pai.0000000000000190] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Pyarokhil AH, Sasaki M, Tomikawa S, Maetani A, Yuhara K, Kobayashi Y, Kitamura N. Immunohistochemical Study of Endocrine Cells in the Stomach and Small Intestine of the Lion (Panthera leo). MAMMAL STUDY 2017. [DOI: 10.3106/041.042.0308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Asadullah Hamid Pyarokhil
- Laboratory of Veterinary Anatomy, Department of Basic Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
- United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
- Preclinical Department, Faculty of Veterinary Science, Kabul University, Kabul, Afghanistan
| | - Motoki Sasaki
- Laboratory of Veterinary Anatomy, Department of Basic Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
- United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
| | | | - Ayami Maetani
- United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
- Nippon Beet Sugar Manufacturing Co., Ltd., Obihiro 080-0831, Japan
| | | | - Yoshiyasu Kobayashi
- United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
- Laboratory of Veterinary Pathology, Department of Basic Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
| | - Nobuo Kitamura
- Laboratory of Veterinary Anatomy, Department of Basic Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
- United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
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Rindi G, Torsello A, Locatelli V, Solcia E. Ghrelin Expression and Actions: A Novel Peptide for an Old Cell Type of the Diffuse Endocrine System. Exp Biol Med (Maywood) 2016; 229:1007-16. [PMID: 15522836 DOI: 10.1177/153537020422901004] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Ghrelin is a gastric peptide involved in food intake control and growth hormone release. Its cell localization has been defined in distinct ghrelin cells of the gastric mucosa in humans and other mammals. Ghrelin production was also described in a number of other sites of the diffuse endocrine system, including the pituitary, thyroid, lung, pancreas, adrenal gland, and intestine. In addition, ghrelin cells were identified early during fetal life and in the placenta and gonads. Finally, endocrine growths and tumors of the diffuse endocrine system may present ghrelin-producing cells, and in a few cases high levels of circulating ghrelin were reported. Besides its well-defined orexigenic role, ghrelin is likely to exert a local paracrine role similar to other brain-gut axis hormones. This review aims to summarize recent data on ghrelin cell distribution in the diffuse endocrine system and discuss local and general ghrelin function during development, adulthood, and endocrine tumor development.
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Affiliation(s)
- Guido Rindi
- Department of Pathology, University of Parma, Italy.
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La Rosa S, Vanoli A. Republished: gastric neuroendocrine neoplasms and related precursor lesions. Postgrad Med J 2015; 91:163-73. [PMID: 25740317 DOI: 10.1136/postgradmedj-2014-202515rep] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Gastric neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours showing different clinicopathological features and behaviour, implying a wide spectrum of therapeutic options. They are currently classified using the 2010 WHO classification of digestive neuroendocrine neoplasms into G1-neuroendocrine tumours (NETs), G2-NETs, neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs). However, most gastric NENs are composed of ECL-cells (ECL-cell NETs) that can be preceded by ECL-cell hyperplastic and dysplastic lesions, whose oncologic potential has not yet been completely elucidated. ECL-cell NETs differ considerably in terms of prognosis depending on the proliferative status and clinicopathological background. The integration of both aspects in the diagnostic pathway may help to better classify tumours in different prognostic categories, especially when diagnosing them in small bioptic specimens. NECs are all poorly differentiated, highly aggressive carcinomas, while MANECs can show different morphological features that are directly associated with different prognoses. Precursor lesions of such carcinomas are not entirely understood. In this review, the clinicopathological features of gastric NENs and related precursor lesions will be described to give the reader a comprehensive overview on this topic.
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Lee JE, Lee HS, Choi SH, Ku SK. The regional distribution and frequency of endocrine cells in the Korean golden frog,Rana plancyi chosenica: an immunohistochemical study. Anim Cells Syst (Seoul) 2014. [DOI: 10.1080/19768354.2014.936505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Abstract
Gastric neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours showing different clinicopathological features and behaviour, implying a wide spectrum of therapeutic options. They are currently classified using the 2010 WHO classification of digestive neuroendocrine neoplasms into G1-neuroendocrine tumours (NETs), G2-NETs, neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs). However, most gastric NENs are composed of ECL-cells (ECL-cell NETs) that can be preceded by ECL-cell hyperplastic and dysplastic lesions, whose oncologic potential has not yet been completely elucidated. ECL-cell NETs differ considerably in terms of prognosis depending on the proliferative status and clinicopathological background. The integration of both aspects in the diagnostic pathway may help to better classify tumours in different prognostic categories, especially when diagnosing them in small bioptic specimens. NECs are all poorly differentiated, highly aggressive carcinomas, while MANECs can show different morphological features that are directly associated with different prognoses. Precursor lesions of such carcinomas are not entirely understood. In this review, the clinicopathological features of gastric NENs and related precursor lesions will be described to give the reader a comprehensive overview on this topic.
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Abstract
Important progress has been made during the last decade in the histopathologic characterization and overall prognostic evaluation of gut neuroendocrine tumors. However, some issues like tumor histogenesis, typing, functional characterization, and preferred site of origin deserve further clarification. This is a survey of the present status of the matter outlining some of the open points. In particular, careful comparison of normal gut endocrine cell types with related endocrine tumors so far identified shows an unexplained lack of neoplasms involving upper small intestine cells like secretin, cholecystokinin, motilin, and GIP cells, as well as the equally unexplained concentration of serotonin EC cell tumors in the ileum and appendix or of somatostatin cell tumors in the duodenal papillary region, despite their wide distribution in the normal gut, not to mention gastrinomas arising in the pancreas, normally devoid of gastrin cells. Special functional (e.g., achlorhydria-driven hypergastrinemia) or pathologic (as chronic inflammation) conditions may locally influence the proliferative and differentiation state of the endocrine cells thus promoting tumor growth. Tumor histologic structure, differentiation level, and proliferative index as well as gastrointestinal wall barriers to tumor diffusion may account for most prognostic parameters, with considerable changes, however, according to the tumor type and site. Thus, further work is needed to develop tumor- and site-adjusted prognostic parameters.
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Affiliation(s)
- Enrico Solcia
- Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy,
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Gilor C, Gilor S, Graves TK, Borst LB, Labelle P, Ridge TK, Santoro D, Dossin O. Distribution of K and L cells in the feline intestinal tract. Domest Anim Endocrinol 2013; 45:49-54. [PMID: 23751572 DOI: 10.1016/j.domaniend.2013.04.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 04/23/2013] [Accepted: 04/26/2013] [Indexed: 12/25/2022]
Abstract
Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)-1 and GLP-2 are hormones secreted from specialized K cells (GIP) and L cells (GLP-1, GLP-2) in the intestinal mucosa. These hormones play major roles in health and disease by modulating insulin secretion, satiety, and multiple intestinal functions. The aim of this study was to describe the distribution of K cells and L cells in the intestines of healthy cats. Samples of duodenum, mid-jejunum, ileum, cecum, and colon were collected from 5 cats that were euthanized for reasons unrelated to this study and had no gross or histologic evidence of gastrointestinal disease. Samples stained with rabbit-anti-porcine GIP, mouse-anti-(all mammals) GLP-1, or rabbit-anti-(all mammals) GLP-2 antibodies were used to determine the number of cells in 15 randomly selected 400× microscopic fields. In contrast to other mammals (eg, dogs) in which K cells are not present in the ileum and aborally, GIP-expressing cells are abundant throughout the intestines in cats (>6/high-power field in the ileum). Cells expressing GLP-1 or GLP-2 were most abundant in the ileum (>9/high-power field) as in other mammals, but, although GLP-1-expressing cells were abundant throughout the intestines, GLP-2-expressing cells were rarely found in the duodenum. In conclusion, the distribution of GIP-secreting K cells in cats is different from the distribution of K cells that is described in other mammals. The difference in distribution of GLP-2- and GLP-1-expressing cells suggests that more than 1 distinct population of L cells is present in cats.
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Affiliation(s)
- C Gilor
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
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Neuroendocrine proliferations of the stomach: a pragmatic approach for the perplexed pathologist. Adv Anat Pathol 2013; 20:148-57. [PMID: 23574771 DOI: 10.1097/pap.0b013e31828d185d] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The classifications of neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors in the stomach are complicated and relatively inaccessible to nonspecialists. Consequently, these lesions tend to remain widely underdiagnosed until they progress to easily recognizable neuroendocrine tumors. This review provides simple, yet rigorous guidelines on how to recognize, classify, and diagnose the neuroendocrine proliferations found in the stomach, emphasizing the most common background in which they arise, atrophic gastritis. After a succinct outline of the types and distribution of the neuroendocrine cells in the normal gastric mucosa we discuss the most common situations in which the pathologist needs to think about gastric neuroendocrine cells. In general practice gastric biopsy specimens are often numerically and topographically inadequate for the evaluation of atrophic gastritis; therefore, we have included an algorithm to address specifically the steps that should be taken when confronted with suboptimal sampling. Finally, we illustrate the suggested diagnostic process with 4 cases that are fairly representative of the type of situations encountered in everyday practice. The pathologist who follows our simple steps will be better aware of this neglected area of gastric pathology and will learn to suspect, recognize, and accurately diagnose the most common abnormalities of the neuroendocrine system in the stomach.
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Suzuki K, Noda Y, Fujita N, Hirasawa D, Obana T, Sugawara T, Ohira T, Harada Y, Maeda Y, Koike Y, Yamagata T, Kusaka J, Tanaka M, Sawai T, Kurose A. Clinicopathological study on endocrine cell micronests associated with early gastric cancer. Intern Med 2013; 52:1311-6. [PMID: 23774539 DOI: 10.2169/internalmedicine.52.9229] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE The purpose of this study was to review cases of early gastric cancer associated with Endocrine cell micronests (ECM) and investigate the incidence and characteristics of these lesions. METHODS A total of 482 patients who had undergone endoscopic or surgical resection for gastric epithelial neoplasms from April 2008 to March 2010 were enrolled in this study. After detection of ECM in the lamina propria mucosa by histological examination of the resected specimens with hematoxilin-eosin staining, immunostaining was also performed. Clinical manifestation and endoscopic findings, as well as histological findings, were examined. RESULTS Among the 482 patients, 5 (1.0%) had ECM. The histological type of gastric epithelial cancers associated with ECM was tubular adenocarcinoma and carcinoma in situ (Tis) in the WHO classification in all 5 cases. ECM were round to oval or trabecular and located within the area of the early gastric cancer in all the 5 cases. The background gastric mucosa was Type A gastritis in 2 patients and ordinary atrophic gastritis in 2 patients. In the other case, it was difficult to determine the type of gastritis. CONCLUSION ECM developed not only from the background of Type A gastritis but also from ordinary atrophic gastritis. ECM coexistent with gastric cancer were present in 1.0% of resectable gastric epithelial neoplasms.
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Affiliation(s)
- Kenjiro Suzuki
- Department of Gastroenterology, Sendai City Medical Center, Japan.
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Guillory B, Splenser A, Garcia J. The Role of Ghrelin in Anorexia–Cachexia Syndromes. ANOREXIA 2013; 92:61-106. [DOI: 10.1016/b978-0-12-410473-0.00003-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Lee CH, Kim DK, Yook TH, Sasaki M, Kitamura N. Effectiveness of electroacupuncture at Zusanli (ST36) on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function. J Acupunct Meridian Stud 2012; 5:63-71. [PMID: 22483184 DOI: 10.1016/j.jams.2012.01.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2011] [Revised: 10/05/2011] [Accepted: 11/30/2011] [Indexed: 11/24/2022] Open
Abstract
The purpose of this study was to examine the effects of electroacupuncture at Zusanli on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function. The authors investigated the histochemical changes of mucous substances and immunohistochemical density of gastrin, serotonin, calcitonin gene-related peptide (CGRP), insulin, and pancreatic polypeptide (PP) secreting cells in rats. Staining density of mucous substances and the enteroendocrine cells of the gastrointestinal tract was observed with histochemical and immunohistochemical methods. Stainless steel needles with a diameter of 0.25 mm were inserted into Zusanli (St36, 5mm below the head of the fibula under the knee joint, and 2mm lateral to the anterior tubercle of the tibia) and connected to an electrical stimulator. The electroacupuncture (EA) stimulation was delivered for 30 minutes at 10 mA, 2 Hz in EA stimulation (2EA group) or 4 Hz in EA stimulation (4EA group) in each experimental group. In 4EA stimulation at the Zusanli, staining density of Alcian blue-periodic acid-Schiff on mucous substances of the stomach body was stronger than those of the 2EA and control groups. Periodic acid-Schiff staining density of pyloric mucosa in the 4EA group was stronger than that of the 2EA and control groups. The immunohistochemical staining density of gastrin, serotonin, and CGRP-secreting cells of pylorus in the 2EA and 4EA groups was stronger than that of the control group. Immunohistochemical staining density of insulin and PP secreting cells of islets of the pancreas in the 2EA and 4EA groups was stronger than that of the control group. These results suggest that EA stimulus at St36 has the potential to influence gastric mucous substances and enteroendocrine cells (gastrin, serotonin, CGRP, insulin, and PP) that subsequently modulate digestive functions.
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Affiliation(s)
- Chang Hyun Lee
- Department of Anatomy, College of Oriental Medicine, Woosuk University, Chonbuk, Korea
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Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Hum Pathol 2011; 42:1373-84. [PMID: 21531442 DOI: 10.1016/j.humpath.2011.01.018] [Citation(s) in RCA: 137] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2010] [Revised: 01/22/2011] [Accepted: 01/28/2011] [Indexed: 12/13/2022]
Abstract
Gastric neuroendocrine neoplasms differ considerably in histology, clinicopathologic background, stage, and patient outcome, implying a wide spectrum of therapeutic options, hence the need for improved diagnostic and prognostic criteria to select appropriate therapy. Here, we tested the European NeuroEndocrine Tumor Society and the novel World Health Organization 2010 grade and stage classifications together with additional clinicopathologic and histologic parameters in a series of 209 gastric neuroendocrine neoplasms with a median follow-up of 89 months. Fifty-one grade 3 neuroendocrine carcinomas and 15 mixed endocrine-exocrine carcinomas of poor outcome were separated from 143 neuroendocrine tumors, including 132 G1 or G2 enterochromaffin-like (ECL) cell neoplasms and 11 G1 gastrin-cell, somatostatin-cell, or serotonin-cell tumors. Most G1 cases had excellent prognosis, even when metastatic, whereas G2 and G3 neoplasms had worse or very severe prognosis, respectively. The European NeuroEndocrine Tumor Society-World Health Organization 2010 proliferative grading system well correlated with patient survival. Structural histologic parameters were equally predictive and when combined with the European NeuroEndocrine Tumor Society-World Health Organization 2010 grading system in a "global grade" improved tumor prognostic stratification. The European NeuroEndocrine Tumor Society-World Health Organization 2010 staging system proved effective. Introduction of novel T (T(1a) and T(1b) or deep submucosal) and N categories (N(1), <3 nodes metastases; N(2), ≥3) allowed a simplified, equally informative 3-stage TNM system. Such improved diagnostic and prognostic criteria for gastric neuroendocrine neoplasms are proposed and discussed.
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20
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Lee HS, Choi SH, Ku SK. Regional distribution and relative frequency of gastrointestinal endocrine cells in the ddN mice: an immunohistochemical study. Anat Histol Embryol 2010; 39:521-8. [PMID: 20712802 DOI: 10.1111/j.1439-0264.2010.01024.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract - fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the ddN mouse, were studied with immunohistochemical method using seven types of antisera against chromogranin (Cg) A serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP). In the GI tract of ddN mice, CgA, serotonin, somatostatin, glucagon, gastrin, CCK-8 immunoreactive (IR) cells were identified with various frequencies, but hPP-IR cells were not observed in this study. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) whereas cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. They showed the highest frequency in the pylorus or colon. CgA-IR cells were observed from the pylorus to ileum. Serotonin-IR cells were detected throughout the whole GI tract except for the fundus. Somatostatin-IR cells were demonstrated throughout the whole GI tract except for the cecum and colon. Gastrin and CCK-8-IR cells were restricted to the pylorus and duodenum. In addition, a few glucagon-IR cells were restricted to the fundus and rectum. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the ddN mouse was similar to that of other strains of mice. However, some strain and/or species-dependent unique distributions and frequencies of endocrine cells were also observed in the present study.
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Affiliation(s)
- H S Lee
- Department of Clinical Laboratory Science, College of Health and Therapy, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea
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21
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The activity of gastric ghrelin positive cells in obese patients treated surgically. Folia Histochem Cytobiol 2010; 47:307-13. [PMID: 19995718 DOI: 10.2478/v10042-009-0033-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Ghrelin is a 28 amino acid peptide hormone regulating food intake and stimulating releasement of growth hormone. It is produced in a distinct endocrine call known as X/A - like cells. The most abundant source of this very important factor in energy homeostasis is gastric fundus. Regulatory mechanisms of ghrelin synthesis and secretion in physiological and pathological states are not discovered completely. The aim of our study was evaluation of the activity of gastric X/A-like cells in obese patients before and after the most popular surgical bariatric procedures - Roux - Y Gastric Bypass (RYGB) and Laparoscopic Adjustable Gastric Banding (LAGB). Obese patients in number 18 took part in the study. LAGB was performed in 7 patients and RYGB in 11 patients. Peripheral blood was taken from each patient before operation and first day, seventh day, one month and three months after surgery. Ghrelin level was determined by RIA technique. The specimen of stomach was taken from circular stapler after gastrojejunostomy during RYGB and immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin-immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. Efficiency of bariatric procedures was estimated by EWL- excess weight loss. We observed very strong immunohistochemical reactions of gastric X/A-like cells, accompanied by lower ghrelin plasma concentration, in comparison to the control group. LAGB procedure induced increase of ghrelin plasma level while RYGB procedure induced decrease of this hormone. The main finding of the present study is the hypoactivity of gastric X/A-like cells in obese patients in comparison to the control group.
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Tagliafierro G, Faraldi G, Pozzi MG. Ultrastructure of the pyloric endocrine cells in the cartilaginous fishScyliorhinus stellaris. ACTA ACUST UNITED AC 2009. [DOI: 10.1080/11250008409439468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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24
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Håkanson, Duan Chen, Erik Lindström R. Control of secretion from rat stomach ECL cells in situ and in primary culture. Scandinavian Journal of Clinical and Laboratory Investigation 2009. [DOI: 10.1080/003655101753352059] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
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25
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Distribution and developmental changes in ghrelin-immunopositive cells in the gastrointestinal tract of African ostrich chicks. ACTA ACUST UNITED AC 2009; 154:97-101. [DOI: 10.1016/j.regpep.2009.02.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2008] [Revised: 01/06/2009] [Accepted: 02/03/2009] [Indexed: 11/24/2022]
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26
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Stengel A, Goebel M, Yakubov I, Wang L, Witcher D, Coskun T, Taché Y, Sachs G, Lambrecht NWG. Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa. Endocrinology 2009; 150:232-8. [PMID: 18818289 PMCID: PMC2630900 DOI: 10.1210/en.2008-0747] [Citation(s) in RCA: 255] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hypothalamic nesfatin-1, derived from the nucleobindin2 (NUCB2) precursor, inhibits nocturnal food intake and body weight gain in rats. Nesfatin-1 is able to cross the blood-brain barrier, suggesting a peripheral source of nesfatin-1. Many centrally acting food intake regulatory neuropeptides are also produced in the periphery, especially in the gastrointestinal tract. Therefore, we investigated the gene expression of NUCB2 and distribution of nesfatin-1-immunoreactive cells in the stomach. Microarray mRNA expression profiles in purified small endocrine cells of the gastric mucosa substantiated by quantitative RT-PCR showed significantly higher NUCB2 mRNA expression compared with brain and heart. Western blot confirmed the expression of NUCB2 protein and its transport into a secretory soluble fraction of gastric mucosal endocrine cell homogenates. Immunohistochemical colabeling for nesfatin-1 and ghrelin, histidine decarboxylase, or somatostatin revealed two subtypes of nesfatin-1-positive endocrine cells. Cells in the midportion of the glands coexpressed nesfatin-1 and ghrelin, whereas few cells in the glandular base coexpressed nesfatin-1 and somatostatin or histidine decarboxylase. High-resolution three-dimensional volume imaging revealed two separate populations of intracytoplasmic vesicles in these cells, one containing nesfatin-1 and the other ghrelin immunoreactivity. Microarray rat genome expression data of NUCB2 in small gastric endocrine cells confirmed by quantitative RT-PCR showed significant down-regulation of NUCB2 after 24 h fasting. In summary, NUCB2 mRNA expression as well as protein content is present in a specific subset of gastric endocrine cells, most of which coexpress ghrelin. NUCB2 gene expression is significantly regulated by nutritional status, suggesting a regulatory role of peripheral nesfatin-1 in energy homeostasis.
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Affiliation(s)
- Andreas Stengel
- CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, University of California, Los Angeles, California, USA
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Santos CM, Nascimento AA, Peracchi AL, Sales A, Mikalauskas JS, Gouveia SF. Immunocytochemical study of gastrintestinal endocrine cells in insectivorous bats (Mammalia: Chiroptera). BRAZ J BIOL 2008; 68:663-9. [DOI: 10.1590/s1519-69842008000300026] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2007] [Accepted: 07/05/2007] [Indexed: 11/22/2022] Open
Abstract
The regional distribution and relative frequency of endocrine cells in the stomach and intestine of Phyllostomidae: Lonchorhina aurita and Molossidae: Molossus molossus bats were studied immunohistochemically. Three types of immunoreactive (IR) endocrine cells - to serotonin (5-HT), gastrin (GAS) and enteroglucagon (GLUC) - were found in the gastric mucosa and four types of IR cells were identified in the intestinal mucosa. This study showed an interespecfic difference in the regional distribution and relative frequency of endocrine cells in the Chiropteran alimentary tract.
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Affiliation(s)
- CM. Santos
- Universidade Federal Rural do Rio de Janeiro, Brazil
| | | | - AL. Peracchi
- Universidade Federal Rural do Rio de Janeiro, Brazil
| | - A. Sales
- Universidade Federal Rural do Rio de Janeiro, Brazil
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28
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Endocrine hyperplasia and dysplasia in the pathogenesis of gastrointestinal and pancreatic endocrine tumors. Gastroenterol Clin North Am 2007; 36:851-65, vi. [PMID: 17996794 DOI: 10.1016/j.gtc.2007.08.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Non-neoplastic proliferative lesions of endocrine cells have been described throughout the gastrointestinal tract and pancreas. A multistep continuum from hyperplasia and dysplasia to neoplasia originally was identified and systematically defined for histamine-producing enterochromaffin-like (ECL) cells of the gastric corpus. More recently, a similar classification system was devised for gastrin (G)- and somatostatin (D)-producing cells in the duodenum. Preneoplastic lesions of the endocrine pancreas still lack a solid and widely accepted definition of a multistep growth process. Similarly, in spite of reports of carcinoid-associated endocrine cell hyperplasia, there is no systematic definition of nonneoplastic lesions of the endocrine cells of the ileum, appendix and colorectum.
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Knezević M, Aleksić-Kovacević S, Aleksić Z. Cell proliferation in pathogenesis of esophagogastric lesions in pigs. ACTA ACUST UNITED AC 2007; 260:1-34. [PMID: 17482903 DOI: 10.1016/s0074-7696(06)60001-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Esophagogastric ulcer is an independent disease in swine that is characterized by ulcerous autodigestion of the cutaneous mucosa, which does not exhibit a tendency to recover, but, on the contrary, a tendency toward severe hemorrhaging, with a predominantly lethal outcome. Since it develops in the part of the stomach that is morphologically and functionally different from other glandular mucosa, it was questioned earlier whether it could be a peptic ulcer based on its nature. Spontaneous ulcers, usually of the stomach, commonly occur in many domestic animals. Some of these lesions are chronic and they may occur in either the glandular or squamous-lined regions of the stomach. As with the human disease, the pathogenesis in domestic animals is multifactorial, poorly understood, and variable between and within species. Environmental stress and dietary factors are very important in the ulcer disease in swine. It has been shown that the Helicobacter spp. is strongly associated with naturally occurring ulcer and preulcer lesions of the pars esophagea in swine, which raises the possibility that Helicobacter spp. is an important factor in the pathogenesis of these lesions. The dynamics of the development of esophagogastric ulcers imply hyperplastic lesions (parakeratosis and hyperkeratosis), keratolysis, erosions, peptic necrosis, and the development of ulcers with all the characteristics of peptic ulcerations in other localities. In addition, K6 is expressed in association with the mucosal changes. The pattern of the intermediate filaments of keratin suggests that epithelial proliferation, which leads to visible hyperkeratosis, constitutes the essence of gastric ulcers in swine.
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Affiliation(s)
- Milijana Knezević
- Department of Pathology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia
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30
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Kidd M, Modlin IM, Eick GN, Champaneria MC. Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells. Am J Physiol Gastrointest Liver Physiol 2006; 291:G778-91. [PMID: 16455786 DOI: 10.1152/ajpgi.00552.2005] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Although the enterochromaffin (EC) cell is one of the primary neuroendocrine regulatory cells of the small intestine, the lack of a purified cell system has precluded characterization of the cell and limited precise physiological evaluation. We developed methodology to obtain a pure population of Mastomys ileal EC cells, evaluated their functional regulation, and defined the transcriptome. Mastomys ilea were everted, end ligated, pronase-collagenase digested, and Nycodenz gradient centrifuged, and EC cells were collected by fluorescence-activated cell sorting (FACS) of acridine orange-labeled cells. Enrichment was confirmed by immunostaining of tryptophan hydroxylase and chromogranin A, specific EC cell markers, serotonin content, EC cell marker gene expression, and electron microscopy. Pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin, and gastrin receptor expression was determined by real-time RT-PCR. Live post-FACS-sorted cells were cultured, and the effects of forskolin, isoproterenol, acetylcholine, GABAA, PACAP-38, and gastrin on serotonin secretion were measured by ELISA. GeneChip Affymetrix profiling of FACS-sorted cells was undertaken to obtain the EC cell transcriptome. FACS produced a >70-fold enrichment of EC cells with a serotonin content of 240 +/- 22 ng/mg protein. Preparations were 99 +/- 0.7% pure by immunostaining for tryptophan hydroxylase. Vasoactive intestinal peptide/PACAP receptor 1 (VPAC1) and somatostatin receptor 2 were present, whereas PACAP receptor 1 (PAC1) and CCK2 receptors were undetectable. Forskolin, isoproterenol, and PACAP-38 stimulated serotonin secretion at EC50 values of 5 x 10(-10), 4.5 x 10(-10), and 1.2 x 10(-9) M, respectively. Isoproterenol stimulated cAMP levels by approximately 3.5 +/- 0.62-fold vs. unstimulated cells (EC50 of approximately 10(-9) M). Octreotide, acetylcholine, and GABAA inhibited serotonin secretion with IC50 values of 3 x 10(-11), 3 x 10(-10), and 2.9 x 10(-10) M, respectively. Gastrin had no effect on serotonin secretion. The naive EC cell transcriptome revealed highly expressed EC cell marker genes, the absence of marker genes for other small intestinal cell types, and a receptor profile that included cholinergic, adrenergic, dopaminergic, serotoninergic, GABAergic, and prostaglandin receptors. We were able to isolate homogeneous preparations (>99%) of live ileal EC cells and demonstrated regulation of serotonin secretion as well as established the normal EC cell transcriptome. Application of this methodology to normal and diseased human ileum will facilitate the elucidation of the pathophysiology of EC cells.
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Affiliation(s)
- M Kidd
- Gastrointestinal Pathobiology Research Group, Yale University School of Medicine, CT, USA
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Abstract
Reactive or chemical gastropathy is the constellation of endoscopic and histological changes caused by chemical injury to the gastric mucosa. Its diagnosis rests on the histopathological demonstration of nonspecific elementary lesions that may occur simultaneously or separately in different degrees and various proportions. These lesions include foveolar hyperplasia, interfoveolar smooth muscle fibers, erosions, edema, and hyperemia, in the absence of significant inflammation. Their respective occurrence in a set of gastric biopsies can be placed on a spectrum of diagnostic certainty that is never absolute because each of such changes can and does occur in other conditions. Although a correlation between histological evidence of chemical gastropathy and clinical manifestations, particularly risk of bleeding, is yet to be documented, reporting the suspicion of drug-induced gastric damage may help clinicians to identify patients that might benefit from change, reduction, or discontinuation of certain medications.
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Affiliation(s)
- Robert M Genta
- Department of Pathology, Geneva University Hospitals, Switzerland.
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Ku SK, Lee HS, Lee JH. The regional distribution and relative frequency of gastrointestinal endocrine cells in the nude mice, Balb/c-nu/nu: an immunohistochemical study. Anat Histol Embryol 2006; 35:104-10. [PMID: 16542175 DOI: 10.1111/j.1439-0264.2005.00645.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract - fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the nude mouse, Balb/c-nu/nu were studied with immunohistochemical method using six types of anti-sera against serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin, glucagon and human pancreatic polypeptide (hPP). All of six types of immunoreactive (IR) cells were identified. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of GI tract. Serotonin-IR cells were detected throughout the whole GI tract and they showed the highest frequency in the pylorus. Gastrin-IR cells were restricted to the pylorus and duodenum with numerous and a few frequencies, respectively. CCK-8-IR cells were also restricted to the pylorus, duodenum and jejunum with numerous, a few and rare frequencies, respectively. Somatostatin-IR cells were demonstrated throughout the whole GI tract except for the colon and rectum, and they showed the highest frequency in the fundus. In addition, glucagon- and hPP-IR cells were restricted to the fundus and rectum, respectively with a few frequencies. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the nude mouse, Balb/c-nu/nu was similar to that of other strains of mice. However, some strain and/or species-dependent unique distributions and frequencies of endocrine cells were also observed especially for somatostatin- and hPP-IR cells.
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Affiliation(s)
- S K Ku
- Pharmacology and Toxicology Laboratory, Dong-Wha Pharmaceutical Industrial Co. Ltd, Anyang 430-017, Repubulic of Korea
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Waisberg J, de Matos LL, do Amaral Antonio Mader AM, Pezzolo S, Eher EM, Capelozzi VL, Speranzini MB. Neuroendocrine gastric carcinoma expressing somatostatin: A highly malignant, rare tumor. World J Gastroenterol 2006; 12:3944-7. [PMID: 16804989 PMCID: PMC4087952 DOI: 10.3748/wjg.v12.i24.3944] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen’s neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.
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Affiliation(s)
- Jaques Waisberg
- Department of Surgery, Faculty of Medicine of ABC, Santo André, Braz.
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Modlin IM, Kidd M, Pfragner R, Eick GN, Champaneria MC. The functional characterization of normal and neoplastic human enterochromaffin cells. J Clin Endocrinol Metab 2006; 91:2340-8. [PMID: 16537680 DOI: 10.1210/jc.2006-0110] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT Neuroendocrine regulation of small intestinal (SI) function is poorly understood because pure neuroendocrine cells are unavailable, whereas the biological basis of SI carcinoid tumors is unknown because neoplastic human enterochromaffin (EC) cells are unavailable. OBJECTIVE The objective of this study was to define the secretory regulation and transcriptome of naive and neoplastic SI neuroendocrine cells. DESIGN EC cells from human ilea were isolated and purified, and a malignant EC cell carcinoid cell line (KRJ-I) was characterized. METHODS Human ilea from right hemicolectomies were pronase/collagenase digested and Nycodenz gradient centrifuged, and EC cells were fluorescence-activated cell sorting (FACS) sorted after acridine orange labeling. Enrichment was defined by immunostaining, gene expression, serotonin (5-HT) content, and real-time RT-PCR. Naive FACS-sorted EC and KRJ-I cells were cultured, and 5-HT secretion was measured after stimulation with forskolin, isoproterenol, acetylcholine, gamma-aminobutyric acid A (GABA(A)), pituitary adenylate cyclase-activating polypeptide (PACAP)-38, and gastrin. Normal and neoplastic EC cell transcriptomes were acquired by Affymetrix profiling (U133A). RESULTS FACS produced 100 +/- 0.3% (chromogranin A staining) and 99 +/- 0.7% pure EC cells by immunostaining for tryptophan hydroxylase with greater than 67-fold enrichment and a 5-HT content of 180 +/- 18 ng/mg protein (mucosa, 3.5 +/- 0.9). Forskolin- and isoproterenol-stimulated 5-HT secretion was 10-100 times more potent for naive cells (EC(50), 1.8 x 10(-9) m; 5.1 x 10(-9) m) than neoplastic cells (EC(50), 2.1 x 10(-7) m; 8.1 x 10(-8) m), but the effect of PACAP-38 was similar (EC(50), 1 x 10(-7) m). Isoproterenol stimulated cAMP levels 1.6 +/- 0.1-fold vs. basal (EC(50), 2.7 x 10(-9) m). Acetylcholine inhibited naive EC cell 5-HT secretion more potently than neoplastic (IC(50), 3.2 x 10(-9) vs. 1.6 x 10(-7) m), whereas GABA(A) was more potent in neoplastic cells (IC(50), 3.9 x 10(-10) vs. 4.4 x 10(-9) m). Octreotide inhibited naive, but not neoplastic, basal 5-HT secretion. Gastrin had no effect on 5-HT secretion. Comparison of naive and neoplastic transcriptomes revealed shared neuroendocrine and EC cell-specific marker genes. Real-time PCR confirmed that expression of adrenergic (beta1), somatostatinergic (SST(R)2), and neural (VPAC(1) and GABA(A)) receptors occurred on both cell types, but PACAP type 1 (PAC(1)) and cholecystokinin type 2 (CCK(2)) were undetectable. The putative carcinoid malignancy genes (MTA1 and MAGE-D2) were unique to the neoplastic EC cell transcriptome. CONCLUSION These data support novel methodology to purify live human EC cells for functional characterization and transcriptome assessment, which will allow identification of new targets to control the secretion and proliferation of SI carcinoids.
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Affiliation(s)
- Irvin M Modlin
- Department of Surgery, TMP202, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
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Gustafsson BI, Bakke I, Tømmerås K, Waldum HL. A new method for visualization of gut mucosal cells, describing the enterochromaffin cell in the rat gastrointestinal tract. Scand J Gastroenterol 2006; 41:390-5. [PMID: 16635905 DOI: 10.1080/00365520500331281] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Enterochromaffin (EC) cells in the gastrointestinal tract have an important function as regulators of secretion, motility and sensation. The EC cell has traditionally been described as bottle-shaped, with basally located stores of serotonin. Stimuli acting on the apical membrane trigger serotonin release, which in turn activates the subepithelial sensory nerve terminals. To better describe the appearance of EC cells, we developed a new method for visualization of mucosal cells. MATERIAL AND METHODS The stomach, small intestine and large intestine were excised from Sprague-Dawley rats and then fixed in formalin. The organs were everted and filled with pronase solution. Single cells and aggregates of formalin-fixed mucosal cells were collected by scraping the mucosa off the muscularis mucosa. EC cells were visualized by staining for immunoreactivity against serotonin. RESULTS EC cells with luminal extensions and very long (up to 80 microM) basally located axon-like extensions, sometimes connecting to neuron-like structures, were found. Other EC cells had no or only short and blunt basal extensions. Dividing serotonin-containing EC cells were also seen. CONCLUSIONS These findings could make an important contribution towards furthering our understanding of EC cell function in gastrointestinal physiology. This new method can also readily be used to give better visualization of the morphology of other mucosal cells.
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Affiliation(s)
- Björn I Gustafsson
- Department of Gastroenterology, St Olav's Hospital HF, Trondheim University Hospital, Trondheim, Norway.
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Locatelli V, Bresciani E, Bulgarelli I, Rapetti D, Torsello A, Rindi G, Sibilia V, Netti C. Ghrelin in gastroenteric pathophysiology. J Endocrinol Invest 2005; 28:843-8. [PMID: 16370568 DOI: 10.1007/bf03347579] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor 1a (GHS-R1a). It is localized in distinct cells of the gastric mucosa, mainly distributed in the mid portion of the oxyntic gland characterized by P/D1 granules in man and X/A-like granules in rodents. The ghrelin cell represents the second most frequent endocrine cell type after the enterochromaffin-like cells in gastric oxyntic mucosa, pointing to a potentially relevant role in the physiology of the stomach. Ghrelin has no relevant homology with any known gastrointestinal peptide and displays strong GH-releasing activity both in animals and in humans. However, in addition to stimulating GH secretion, ghrelin possesses several other endocrine and extraendocrine biological activities that are explained by the widespread distribution of ghrelin and GHS-R1a expression. In the rat, ghrelin exerts a control in gastric acid secretion and motility: the gastric acid secretion is stimulated by peripheral administration of high doses of ghrelin, but inhibited by very low doses of ghrelin delivered into the central nervous system. Moreover, ghrelin provides a potent and dose-related gastroprotective action against ethanol- and stress-induced gastric ulcers. The integrity of both nitric oxide (NO) system and capsaicin afferent nerves are required for the gastroprotective effect of ghrelin, whereas the vagus nerve might be involved in conveying ghrelinergic signal from periphery to the brain. In addition, prostaglandins derived by the constitutive cyclooxygenase (COX) activity are essential for the protective activity of ghrelin in ethanol and stress-induced gastric lesions. Given its prevailing role in physiological and pathophysiological gastric function, the discovery of ghrelin will open new perspectives and potential clinical implications in the gastroenteric field.
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Affiliation(s)
- V Locatelli
- Department of Experimental and Environmental Medicine and Biotechnology, University of Milano-Bicocca, Monza, Italy.
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Abstract
AIM: To clarify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans.
METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum, rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxy-tryptamine (5-HT), somatostatin (SS), gastrin (GAS), glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted.
RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates. Five types of GI endocrine cells, namely 5-HT, SS, GAS, SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus; while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells, which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found throughout the GIT except for jejunum in E. elegans and showed a restricted distribution in the GIT of G. japonicus and S. indicus. In the GIT of four reptiles the region with the highest degree of cell type heterogeneity was pylorus and most types of GI endocrine cells along the GIT showed the peak density in pylorus as well.
CONCLUSION: Some common and unique features of the distribution and morphology of different types of GI endocrine cells are found in four reptiles. This common trait may reflect the similarity in digestive physiology of various vertebrates.
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Affiliation(s)
- Xu-Gen Huang
- Key Laboratories on Conservation and Use of Important Biological Resources of Anhui Province, College of Life Science, Anhui Normal University, Wuhu 241000, Anhui Province, China
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Abstract
Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.
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Affiliation(s)
- Masayasu Kojima
- Molecular Genetics, Institute of Life Science, Kurume University, Hyakunenkouen 1-1, Kurume, Fukuoka 839-0864, Japan.
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Ku SK, Lee HS, Byun JS, Seo BI, Lee JH. Changes of the gastric endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma: An immunohistochemical quantitative study. World J Gastroenterol 2005; 11:1317-23. [PMID: 15761969 PMCID: PMC4250678 DOI: 10.3748/wjg.v11.i9.1317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The regional distributions and relative frequencies of some gastric endocrine cells of C57BL/6 mice were studied by immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon and human pancreatic polypeptide (HPP) after subcutaneous implantation of murine lung carcinoma (3LL) cells.
METHODS: The experimental animals were divided into two groups, one is non-implanted sham and the other is 3LL-implanted group. Samples were collected from the two regions of stomach (fundus and pylorus) at 28 d after implantation of 3LL cells (1×105 cell/mouse).
RESULTS: In this study, all the seven types of immunoreactive (IR) cells were identified except for HPP. Most of these IR cells in the gastric portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found occasionally. The regional distributions of gastric endocrine cells in the 3LL-implanted group were similar to those of non-implanted sham. However, significant decreases of some types of IR cells were detected in 3LL-implanted group compared to those of non-implanted sham. In addition, the IR cells showing degranulation were numerously detected in 3LL-implanted group. CGA-, serotonin- and somatostatin-IR cells in the fundus and pylorus regions, and gastrin-IR cells in the pylorus regions of 3LL-implanted groups significantly decreased compared to those of non-implanted sham. However, no changes on frequencies of CCK-8- and glucagon-IR cells were demonstrated between 3LL-implanted and non-implanted groups.
CONCLUSION: Endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. Implantation of tumor cell mass (3LL) induced severe quantitative changes of gastric endocrine cell density, and the abnormality in density of gastric endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.
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Affiliation(s)
- Sae-Kwang Ku
- Pharmacology and Toxicology Laboratory, Central Research Laboratories, Dong-Wha Pharmaceutical Industrial Co. Ltd, Anyang 430-017, Republic of Korea
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Lee HS, Ku SK. An immunohistochemical study of endocrine cells in the alimentary tract of the grass lizard, Takydromus wolteri Fischer (Laceridae). Acta Histochem 2005; 106:171-8. [PMID: 15147638 DOI: 10.1016/j.acthis.2003.10.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2003] [Revised: 10/23/2003] [Accepted: 10/31/2003] [Indexed: 12/20/2022]
Abstract
Distribution patterns and the relative frequency of different types of endocrine cells were demonstrated in the alimentary tract of the grass lizard, Takydromus wolteri, using nine specific antibodies raised against mammalian regulatory peptides. The alimentary tract of the lizard was divided into six portions from the esophagus to the rectum. Most endocrine cells were found in the epithelial lining and were generally spindle shaped with long cytoplasmic processes ending in the lumen (open cell type), whereas cells that were spherical in shape (closed cell type) were occasionally found in gastric, esophageal and intestinal glands. Endocrine cells were stained for the following regulatory peptides: bovine Sp-1/chromogranin (BCG), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon, insulin, human pancreatic polypeptide (HPP) and secretin. Cells stained for BCG and serotonin were present throughout the entire gastrointestinal tract and they occurred with the highest frequency in stomach and pylorus, respectively. Somatostatin-positive cells were detected throughout the entire gastrointestinal tract except for the esophagus and large intestine, and were most predominant in pylorus and duodenum. Cells stained for gastrin were restricted to the pylorus and duodenum and occurred with a relatively low frequency. CCK-8-positive cells were observed from pylorus to small intestine and showed the highest frequency in the pylorus. Glucagon- and insulin-containing cells were located in duodenum and small intestine but were found only rarely. HPP-stained cells were detected in duodenum and small intestine with the highest frequency in duodenum. Cells stained for secretin were restricted to duodenum and were found only rarely. In conclusion, distribution patterns and the relative frequency of these endocrine cells correspond well with previous reports on distribution patterns of endocrine cells in reptile species but some deviating patterns were also observed.
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Affiliation(s)
- Hyeung Sik Lee
- Department of Herbal Biotechnology, Daegu Haany University, Gyeongsan, Gyeongbuk, 712-715, Republic of Korea.
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41
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Tonelli F, Fratini G, Falchetti A, Nesi G, Brandi ML. Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience. J Intern Med 2005; 257:38-49. [PMID: 15606375 DOI: 10.1111/j.1365-2796.2004.01424.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Multiple endocrine neoplasia type 1 (MEN1) gastro-entero-pancreatic (GEP) tumours develop from the pancreatic islets and from the endocrine cells of the duodenal and gastric mucosa. Even if GEP tumours have generally a benign course, a subgroup of them shows an aggressive behaviour and is a major cause of death amongst MEN1 patients. Diagnosis of insulinoma should lead promptly to pancreatic surgery. MEN1 gastrinomas are multiple and almost exclusively localized in the duodenum. Cure rate for Zollinger-Ellison syndrome in MEN1 is low when surgery is limited to tumour enucleation or full thickness duodenal wall resection. Conversely, pancreatoduodenectomy is followed by higher chance of cure. For nonfunctioning tumours exceeding 1 cm diameter in size a prompt treatment is recommended due to their high malignant potential. Gastroscopic surveillance is indicated for the frequent occurrence of multiple, small, type 2 fundic carcinoids. Endoscopic removal is possible for lesions growing in the mucosa-submucosa, but partial or even total gastrectomy is recommended for the small number of gastric carcinoids infiltrating the muscular layers.
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Affiliation(s)
- F Tonelli
- Department of Clinical Physiopathology, University of Florence, Florence, Italy.
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42
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Kojima M, Hosoda H, Kangawa K. Clinical endocrinology and metabolism. Ghrelin, a novel growth-hormone-releasing and appetite-stimulating peptide from stomach. Best Pract Res Clin Endocrinol Metab 2004; 18:517-30. [PMID: 15533773 DOI: 10.1016/j.beem.2004.07.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Recent identification of novel appetite-regulating hormones has revealed the complex interactions of these humoral factors in the regulation of feeding behavior in mammals. One of these hormones, ghrelin, a natural ligand of the orphan receptor GHS-R, purified from stomach, is able to stimulate growth hormone release from pituitary cells. Ghrelin is a 28 amino acid peptide containing an n-octanoylated serine 3 residue that is essential for its activity. Ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, the region known to control food intake. As an orexigenic peptide, ghrelin is therefore an endogenous regulator of feeding behavior from the peripheral tissues to the central nervous system.
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Affiliation(s)
- Masayasu Kojima
- Molecular Genetics, Institute of Life Science, Kurume-University, Kurume, Fukuoka 839-0861, Japan.
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43
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Ku SK, Lee JH, Lee HS. Immunohistochemical study on the endocrine cells in gut of the stomachless teleost, Zacco platypus (Cyprinidae). Anat Histol Embryol 2004; 33:212-9. [PMID: 15239812 DOI: 10.1111/j.1439-0264.2004.00539.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The regional distribution and relative frequency of neurohormonal peptides-producing cells were demonstrated in the gut of the stomachless teleost, Zacco platypus (Temminck et Schegel), using 10 types of specific antisera raised against mammalian regulatory peptides. The gut of Z. platypus was divided into five portions from proximal to distal (segment I-V). Most of immunoreactive cells in the epithelial lining portion, between epithelial cells, were generally spherical or spindle shape having long cytoplasmic process that was reached via the lumen while cells round in shape were found in the basal portions of epithelial lining occasionally. Serotonin-, somatostatin-, glucagon-, cholecystokinin (CCK)-8 and pancreatic polypeptide (PP)-immunoreactive cells were observed in this study. However, no chromogranin A-, secretin-, vasoactive intestinal peptide (VIP)-, substance P- and bombesin-immunoreactive cells were found. Serotonin-immunoreactive cells were demonstrated throughout the entire gut tract and occurred more frequently than other cells. Somatostatin-immunoreactive cells were restricted to proximal segments of the gut (segment I-III) with rare frequencies, and glucagon-immunoreactive cells were demonstrated in the proximal segments of the gut (segment I, II) with moderate to few occurrences. CCK-8-immunoreactive cells were found throughout the whole intestinal tract except for most proximal segment (segment I) with moderate to few frequencies and PP-immunoreactive cells were demonstrated in the proximal to middle segments, segment I-III, with a few, rare and rare frequencies, respectively.
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Affiliation(s)
- S K Ku
- Pharmacology and Toxicology Laboratory, Central Research Laboratories, Dong-Wha Pharmaceutical Industrial Co, Anyang 430-017, Republic of Korea
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44
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Kanamoto N, Akamizu T, Tagami T, Hataya Y, Moriyama K, Takaya K, Hosoda H, Kojima M, Kangawa K, Nakao K. Genomic structure and characterization of the 5'-flanking region of the human ghrelin gene. Endocrinology 2004; 145:4144-53. [PMID: 15142980 DOI: 10.1210/en.2003-1718] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Ghrelin, an endogenous ligand for the GH secretagogue receptor, induces GH secretion, food intake, and positive energy balance. Although ghrelin exhibits a variety of hormonal actions, the mechanisms regulating ghrelin expression and secretion remain unclear. To understand regulation of human ghrelin gene expression, we examined the genomic structure of approximately 5,000 bp of the 5'-flanking region of the human ghrelin gene. We performed rapid amplification of cDNA ends to estimate transcriptional start sites, indicating that there are two transcriptional initiation sites within the human ghrelin gene. Both transcripts were equally expressed in the human stomach, whereas the longer transcript was mainly expressed in a human medullary thyroid carcinoma (TT) cell line. Functional analysis using promoter-reporter constructs containing the 5'-flanking region of the gene indicated that the sequence residing within the -349 to -193 region is necessary for human ghrelin promoter function in TT cells. Within this region existed several consensus sequences for a number of transactivating regulatory proteins, including an E-box site. Destruction of this site decreased to 40% of the promoter activity. The upstream region of the promoter has two additional putative E-box sites, and site-directed mutagenesis suggested that these are also involved in promoter activation. Electrophoretic mobility shift assays demonstrated that the upstream stimulatory factor specifically bound to these E-box elements. These results suggest a potential role for upstream stimulatory factor transcription factors in the regulation of human ghrelin expression.
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Affiliation(s)
- Naotetsu Kanamoto
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Rindi G, Leiter AB, Kopin AS, Bordi C, Solcia E. The "normal" endocrine cell of the gut: changing concepts and new evidences. Ann N Y Acad Sci 2004; 1014:1-12. [PMID: 15153415 DOI: 10.1196/annals.1294.001] [Citation(s) in RCA: 202] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
The endocrine cells of the gut are a highly specialized mucosal cell subpopulation. Within the gastrointestinal tract at least 14 different cell types produce a wide range of hormones with a specific regional distribution. The gut endocrine cells belong to the diffuse endocrine system. These cells present two regulated pathways of secretion characterized by large dense core vesicles (LDCV) and synaptic-like microvesicles (SLMV). Gut endocrine cells are recognized by the expression of several "general" markers, including the LDCV marker chromogranin A and the SLMV marker synaptophysin, in addition to the cytosolic markers neuron-specific enolase and protein gene product 9.5. The expression of different hormones identifies specific cell types. The gut endocrine cells are reputed to be terminally differentiated and incapable of proliferation. However, some data suggest that the number of gut endocrine cells may adapt in response to tissue-specific physiological stimuli. Gut endocrine cell differentiation appears to follow a "constitutive" tissue-specific pathway, which may be disrupted and investigated by genetic manipulation in mice. It is suggested that endocrine cell homeostasis is maintained by the entry of new endocrine-committed cells along the differentiation pathway and that such intermediate cells may be sensitive to physiological stimuli as well as transforming agents.
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Affiliation(s)
- Guido Rindi
- Department of Pathology and Laboratory Medicine, University of Parma, Italy.
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46
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Ku SK, Lee HS, Lee JH. An Immunohistochemical Study of Gastrointestinal Endocrine Cells in the BALB/c Mouse. Anat Histol Embryol 2004; 33:42-8. [PMID: 15027962 DOI: 10.1111/j.1439-0264.2004.00508.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal tract (GIT) of BALB/c mouse were studied. Endocrine cells were stained using immunohistochemical method with seven types of antisera against bovine chromogranin (BCG), serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin, glucagon and human pancreatic polypeptide (HPP), and the regional distributions and their relative frequencies were observed in the eight portions of the GIT of BALB/c mice. All seven types of immunoreactive (IR) cells were identified. Most of the IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) while round-shaped cells (closed type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies varied according to each portion of the GIT. BCG-IR cells were observed throughout the whole GIT except for the rectum and they were most predominant in the pylorus. Serotonin-IR cells were detected throughout the whole GIT and they showed the highest frequency in the fundus. Gastrin- and CCK-IR cells were restricted to the pylorus and duodenum with a majority in the pylorus and rare or a few frequencies in the duodenum. Compared with other mammals, somatostatin-IR cells were restricted to the fundus and pylorus with a few frequencies, respectively. In addition, glucagon- and HPP-IR cells were restricted to the fundus and duodenum, respectively, with relative low frequencies. Some species-dependent unique distributions and frequencies of endocrine cells were observed in the GIT of BALB/c mouse compared with other rodents.
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Affiliation(s)
- S K Ku
- Department of Biology, Faculty of Basic Science, Kyungsan Univesrity, Kyungsan, Kyungpook, Republic of Korea
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Ku SK, Lee HS, Koh JK, Lee JH. An immunohistochemical study on the neuropeptide-producing endocrine cells in the alimentary tract of wrinkled frog, Rana rugosa (Ranidae). Gen Comp Endocrinol 2003; 131:1-8. [PMID: 12620241 DOI: 10.1016/s0016-6480(02)00642-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The regional distribution and relative frequency of neurohormonal peptides-producing endocrine cells were demonstrated in the alimentary tract of wrinkled frog, Rana rugosa, using eight types of specific antisera raised against mammalian regulatory peptides. The alimentary tract of frog was divided into six portions from esophagus to rectum. Most of the cells in the epithelial lining portion, between epithelial cells, were generally spherical or spindle shaped having long cytoplasmic process that was reached to the lumen (open-typed cell) while cells showing round shape (close-typed cell) were also found in the gastric, esophageal or intestinal glands occasionally. All of eight immunoreactive (IR) cells against serotonin, somatostatin, bovine Sp-1/chromogranin (BCG), gastrin, cholecystokinin (CCK)-8, bombesin, glucagon, and human pancreatic polypeptide (HPP) were observed in this study. Serotonin-IR cells were demonstrated throughout whole alimentary tract including esophagus and showed most predominant frequency in antrum. Somatostatin-IR cells were also detected throughout whole alimentary tract including esophagus and showed most predominant in pylorus and antrum. BCG-IR cells were restricted to stomach regions with relatively low frequencies. CCK-8-IR cells were observed from antrum to ileum and showed highest frequency in antrum. Gastrin-IR cells were restricted to antrum with low frequency and bombesin-IR cells were demonstrated from esophagus to antrum with various frequencies. Glucagon-IR cells were located throughout whole alimentary tract except for rectum and showed most predominant frequency at antrum. HPP-IR cells were detected from antrum to ileum with highest frequency in antrum. In conclusion, the regional distribution and relative frequency of these IR cells correspond well to the previous report in anuran species but somewhat peculiar patterns are also detected.
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Affiliation(s)
- Sae-kwang Ku
- Pharmacology and Toxicology Laboratory, Central Research Laboratories, Dong-Wha Pharmaceutical Industrial Co, Anyang 430-017, Republic of Korea
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48
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Ku SK, Lee HS, Lee JH. An immunohistochemical study of the gastrointestinal endocrine cells in the C57BL/6 mice. Anat Histol Embryol 2003; 32:21-8. [PMID: 12733269 DOI: 10.1046/j.1439-0264.2003.00433.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) of the gastrointestinal tract of C57BL/6 mouse was studied with immunohistochemical method using seven types of specific anti-sera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecystokinin (CCK)-8. In this study, all these seven types of immunoreactive (IR) cells were identified. Most of these IR cells in the intestinal portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of gastrointestinal tract. CGA-IR cells were demonstrated throughout the whole gastrointestinal tract and they showed most predominant in the pylorus and duodenum. Serotonin-IR cells were detected throughout whole gastrointestinal tract and they showed highest frequency in the stomach and colon. Somatostatin-IR cells were demonstrated throughout whole gastrointestinal tract except for large intestine and showed highest frequency in the fundus. HPP-IR cells were found in the fundus with rare frequency. Peculiarly, glucagon-IR cells were restricted to the fundus, ileum and colon with a few frequencies. Gastrin-IR cells were restricted to the pylorus with numerous frequency and CCK-8-IR cells were observed in the pylorus, duodenum and jejunum with numerous and/or a few frequencies, respectively. In conclusion, some peculiar distributional patterns of gastrointestinal endocrine cells were found in C57BL/6 mouse.
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Affiliation(s)
- S K Ku
- Pharmacology and Toxicology Laboratory, Central Research Laboratories, Dong-Wha Pharmaceutical Industrial Co., Ltd, Anyang 430-017, Republic of Korea
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49
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Ku SK, Lee JH, Lee HS, Park KD. The regional distribution and relative frequency of gastrointestinal endocrine cells in SHK-1 hairless mice: an immunohistochemical study. Anat Histol Embryol 2002; 31:78-84. [PMID: 12047243 DOI: 10.1046/j.1439-0264.2002.00362.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum, caecum, colon and rectum) of the gastrointestinal tract of SKH-1 hairless mice were investigated using immunohistochemical methods and seven types of specific antisera against somatostatin, serotonin, glucagon, cholecystokinin (CCK)-8, secretin, pancreatic polypeptide (PP) and gastrin. In this study, somatostatin-, serotonin-, glucagon-, CCK-8-, secretin- and gastrin-immunoreactive (IR) cells were identified. Most of these IR cells in the intestinal portion were generally spherical or spindle-shaped (open-type cell) while cells that were round in shape (close-type cell) were occasionally found in the stomach regions. Their relative frequencies were varied according to each portion of gastrointestinal tract. Somatostatin-IR cells were found throughout the gastrointestinal tract except for the large intestine. Serotonin-IR cells were detected throughout the whole gastrointestinal tract and were the most predominant endocrine cell types in this species of mouse. Glucagon-IR cells were restricted to the fundus, occurring rarely. CCK-8-IR cells were observed in the pylorus, duodenum and jejunum with frequencies that were numerous, moderate and few, respectively. Peculiarly, secretin-IR cells were demonstrated in the whole intestinal tract with either few or rare frequencies. Gastrin-IR cells were restricted to the pylorus and were numerous. However, no PP-IR cells were found in this study. In conclusion, some peculiar distributional patterns of gastrointestinal endocrine cells were found in SKH-1 hairless mouse.
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Affiliation(s)
- S-K Ku
- Pharmacology & Toxicology Laboratory, Dong-Wha Pharmaceutical Industrial Co, Anyang 430-017, Korea
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50
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Sakata I, Nakamura K, Yamazaki M, Matsubara M, Hayashi Y, Kangawa K, Sakai T. Ghrelin-producing cells exist as two types of cells, closed- and opened-type cells, in the rat gastrointestinal tract. Peptides 2002; 23:531-6. [PMID: 11836003 DOI: 10.1016/s0196-9781(01)00633-7] [Citation(s) in RCA: 215] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the growth-hormone secretagogue receptor (GHS-R) and is known to exist in the gastrointestinal tract and hypothalamus. In this study, we investigated in detail the distribution and morphologic characteristics of ghrelin-containing cells (ghrelin cells) in the gastrointestinal tract by immunohistochemistry and in situ hybridization. Ghrelin cells were found to be localized in the mucous membrane of the stomach, duodenum, ileum, cecum and colon but not in myenteric plexus, and they can be classified into open- and closed-type cells. The greatest number of ghrelin cells was found in the stomach, and it was found that the number of the opened-type cells gradually increased in the direction from stomach to the lower gastrointestinal tract. These results suggest that the two types of ghrelin cells may be distinctly regulated and play different physiological roles in various regions of the gastrointestinal tract.
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Affiliation(s)
- Ichiro Sakata
- Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Saitama, 338-8570, Saitama, Japan
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