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Mucosal Immunology Jan 2013Enterochromaffin (EC) cells in the gastrointestinal (GI) mucosa are the main source of serotonin (5-hydroxytryptamine (5-HT)) in the body. 5-HT is implicated in the...
Enterochromaffin (EC) cells in the gastrointestinal (GI) mucosa are the main source of serotonin (5-hydroxytryptamine (5-HT)) in the body. 5-HT is implicated in the pathophysiology of many GI disorders including functional and inflammatory bowel disorders. Herein we studied the role of interleukin 13 (IL-13) in EC cell biology by utilizing IL-13-deficient (IL-13-/-) mice and BON cells (a model for human EC cells). The numbers of EC cells and 5-HT amount were significantly lower in enteric parasite, Trichuris muris-infected IL-13-/- mice compared with the wild-type mice. This was accompanied with increased parasite burden in IL-13-/- mice. Treatment of naive and infected IL-13-/- mice with IL-13 increased EC cell numbers and 5-HT amount. BON cells expressed IL-13 receptor and in response to IL-13 produced more 5-HT. These results provide novel information on IL-13-mediated immunological control of 5-HT in the gut, which may ultimately lead to improved therapeutic opportunities in various GI disorders.
Topics: Animals; Cell Line; Enterochromaffin Cells; Gastrointestinal Tract; Humans; Hyperplasia; Interleukin-13; Male; Mice; Mice, Knockout; Mucous Membrane; Serotonin; Trichuriasis; Trichuris; Tryptophan Hydroxylase
PubMed: 22763407
DOI: 10.1038/mi.2012.58 -
Acta Histochemica 1976As a result of investigations active biosynthesis of melatonin was found in enterochromaffin cells of gastrointestinal tract. It is suggested to unify epiphysis and...
As a result of investigations active biosynthesis of melatonin was found in enterochromaffin cells of gastrointestinal tract. It is suggested to unify epiphysis and enterochromaffine cells into a united functionally active neuroendocrine system, which plays an important role in the control of rhythms of biological processes in the body.
Topics: Animals; Appendicitis; Biological Assay; Biological Clocks; Cell Count; Chromaffin System; Enterochromaffin Cells; Humans; Melanophores; Melatonin; Rabbits
PubMed: 818867
DOI: 10.1016/S0065-1281(76)80092-X -
Annals of the New York Academy of... Apr 2004The peptide hormone gastrin is the key regulator of gastric acid secretion. Gastrin exerts its effects as acid secretagogue through functional activation of gastric... (Review)
Review
The peptide hormone gastrin is the key regulator of gastric acid secretion. Gastrin exerts its effects as acid secretagogue through functional activation of gastric enterochromaffin-like (ECL) cells, which control acid secretion through biosynthesis and release of histamine. In ECL cells, concerted activation of histidine decarboxylase (HDC), vesicular monoamine transporter 2 (VMAT2), and chromogranin A (CgA) genes by gastrin is a prerequisite for proper acid control. To elucidate the molecular pathways underlying gastrin-dependent control of ECL cell genes, we recently analyzed the signaling cascades, regulatory promoter elements, and transcription factors mediating the transcriptional effects of gastrin. Our studies identified the Raf>MEK1>ERK 1/-2 kinase module as the common signaling pathway mediating gastrin-dependent ECL cell gene transcription. In contrast to this uniform signaling cascade, pronounced heterogeneity was detected between cis- and trans-activating regulatory factors conferring gastrin responsiveness. The molecular diversity of transcription factors and regulatory enhancer elements transmitting gastrin-triggered gene transcription offers the molecular basis for synergistic, but differential, regulation of HDC, VMAT2, and CgA genes during a secretory challenge of ECL cells by gastrin and possibly other acid secretagogues.
Topics: Animals; Enterochromaffin Cells; Gastrins; Gene Expression Regulation; Humans; Signal Transduction
PubMed: 15153424
DOI: 10.1196/annals.1294.010 -
Regulatory Peptides Mar 1995A rapid induction of enterochromaffinlike (ECL) cell tumours has been shown in Praomys (Mastomys) natalensis subjected to histamine2-receptor blockade. In the present...
A rapid induction of enterochromaffinlike (ECL) cell tumours has been shown in Praomys (Mastomys) natalensis subjected to histamine2-receptor blockade. In the present study the reversibility of ECL cell proliferation induced by acid inhibition was investigated. Short-term treatment (8 weeks) with the histamine2-receptor antagonist loxtidine caused a moderate hypergastrinemia, accompanied by a minor increase in histamine contents and a 2-fold increased volume density of the endocrine cells in gastric oxyntic mucosa. Eight weeks after withdrawal of treatment the volume density of endocrine cells was normalised as were the tissue levels of histamine, indicating a total reversibility of ECL cell hyperplasia. Long-term treatment (24 weeks) caused severe changes in the endocrine cell population of the oxyntic mucosa with neoplasia (5/21), dysplasia (11/21) and nodular hyperplasia (5/21). The endocrine cell density increased twofold and tissue histamine levels fourfold. 24 weeks after cessation of treatment, the endocrine cell density had decreased to 136% of controls, while histamine concentrations were normalised. The frequency of invasive carcinoids after recovery (4/23) differed only slightly from that seen after treatment for 24 weeks (5/21). Dysplastic lesions were only seen in 1/23 and hyperplastic lesions were of less severe type after recovery. The results demonstrate that ECL cell hyperplasia and dysplasia, induced by acid inhibition, are reversible after cessation of treatment. However, ECL cell tumours did not disappear, within the given observation period. One may therefore speculate that ECL cell proliferation is no longer reversible once the neoplastic (transformed) phenotype has developed.
Topics: Animals; Carcinoid Tumor; Cell Count; Cell Division; Cell Transformation, Neoplastic; Enterochromaffin Cells; Female; Gastrins; Histamine; Histamine H2 Antagonists; Hyperplasia; Male; Muridae; Parietal Cells, Gastric; Stomach Neoplasms; Triazoles
PubMed: 7770630
DOI: 10.1016/0167-0115(95)00123-s -
Gastroenterology Apr 1996Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide,...
BACKGROUND & AIMS
Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, serotonin, gamma-amino-butyric acid, neurokinins A and B, neurotensin, neuropeptide Y, peptide YY, gastrin-releasing peptide, somatostatin, and [Met5]enkephalin. Although some of these agents have been implicated as regulators of gastric acid secretion, their site and mechanism of action is not well understood. The aim of this study was to investigate whether local gastric neurotransmitters modulate acid secretion by regulating basal and gastrin-driven enterochromaffin-like (ECL) cell histamine release.
METHODS
The effects of the above agents were investigated in a short-term 90%-95% pure ECL cell culture system. Cells were incubated with either the neuromodulator alone or in combination with gastrin for 10-40 minutes, and histamine secretion was measured by enzyme immunoassay.
RESULTS
Acetylcholine, isoproterenol, and vasoactive intestinal polypeptide significantly stimulated basal and gastrin-driven histamine secretion, whereas calcitonin gene-related peptide and somatostatin inhibited basal and gastrin-driven histamine secretion. The M1 muscarinic receptor antagonist pirenzepine dose dependently inhibited the action of acetylcholine, whereas the M3 receptor antagonist 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride had no effect. the rest of the evaluated agents had no effect on ECL cell histamine secretion.
CONCLUSIONS
These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.
Topics: Acetylcholine; Adrenergic Agents; Analysis of Variance; Animals; Calcitonin Gene-Related Peptide; Cells, Cultured; Enterochromaffin Cells; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Histamine Release; Neurotransmitter Agents; Rats; Somatostatin; Vasoactive Intestinal Peptide
PubMed: 8612997
DOI: 10.1053/gast.1996.v110.pm8612997 -
Cancer Nov 1981A case of rectal carcinoid tumor in a 79-year-old Japanese man is reported. The tumor, 1.5 x 0.9 cm, was localized in both mucosa and submucosa of the rectum with...
A case of rectal carcinoid tumor in a 79-year-old Japanese man is reported. The tumor, 1.5 x 0.9 cm, was localized in both mucosa and submucosa of the rectum with neither invasion nor metastasis. Microscopically, neoplastic cells were mainly arranged in rosette-like and trabecular structures within thin fibrous stroma. Histochemically, both argyrophil and argentaffin reactions were positive. At the ultrastructural level, two distinctive types of neurosecretory granules were found in the cytoplasm of tumor cells.
Topics: Aged; Carcinoid Tumor; Enterochromaffin Cells; Humans; Male; Rectal Neoplasms
PubMed: 7296518
DOI: 10.1002/1097-0142(19811101)48:9<2103::aid-cncr2820480931>3.0.co;2-# -
Journal of Visualized Experiments : JoVE Oct 2019Small bowel neuroendocrine tumors (SBNETs) are rare cancers originating from enterochromaffin cells of the gut. Research in this field has been limited because very few...
Small bowel neuroendocrine tumors (SBNETs) are rare cancers originating from enterochromaffin cells of the gut. Research in this field has been limited because very few patient derived SBNET cell lines have been generated. Well-differentiated SBNET cells are slow growing and are hard to propagate. The few cell lines that have been established are not readily available, and after time in culture may not continue to express characteristics of NET cells. Generating new cell lines could take many years since SBNET cells have a long doubling time and many enrichment steps are needed in order to eliminate the rapidly dividing cancer-associated fibroblasts. To overcome these limitations, we have developed a protocol to culture SBNET cells from surgically removed tumors as spheroids in extracellular matrix (ECM). The ECM forms a 3-dimensional matrix that encapsulates SBNET cells and mimics the tumor micro-environment for allowing SBNET cells to grow. Here, we characterized the growth rate of SBNET spheroids and described methods to identify SBNET markers using immunofluorescence microscopy and immunohistochemistry to confirm that the spheroids are neuroendocrine tumor cells. In addition, we used SBNET spheroids for testing the cytotoxicity of rapamycin.
Topics: Enterochromaffin Cells; Humans; Immunohistochemistry; Intestinal Neoplasms; Intestine, Small; Neuroendocrine Tumors; Pancreatic Neoplasms; Spheroids, Cellular; Stomach Neoplasms; Tumor Cells, Cultured; Tumor Microenvironment
PubMed: 31657801
DOI: 10.3791/60303 -
General Pharmacology Mar 19971. The purpose of this study was to examine the change in gastric acid output and gastric erosion formation produced by inducing gastric enterochromaffin-like (ECL) cell... (Comparative Study)
Comparative Study
1. The purpose of this study was to examine the change in gastric acid output and gastric erosion formation produced by inducing gastric enterochromaffin-like (ECL) cell hyperplasia in female rats. 2. Rats were treated with vehicle or ranitidine (1,200 mumol/kg/day x 4 wks) administered via SC Alzet minipumps. Experiments were performed 24 hours after removing the minipump, when the inhibitory effect of ranitidine on gastric acid secretion had been lost. 3. Basal gastric acid secretion was 7-fold higher in chronic ranitidine animals than in sham control. 4. Both total and net gastric acid secretions stimulated by carbachol/pentagastrin infusion or histamine injection were significantly higher in the chronic ranitidine animals than in controls. 5. By contrast, intracisternal injection of the chemical vagal stimulant RX77368 (100 ng) resulted in no net increase in acid output of recovered ranitidine-pretreated group. 6. No significant changes in gastric erosions produced experimentally by cold exposure plus restraint or indomethacin pretreatment were noted in recovered chronic ranitidine animals compared to sham controls. 7. These findings suggest that achlorhydria-induced ECL cell hyperplasia augments both basal and stimulated gastric acid secretory function. The histamine results implicate an enhanced parietal cell mass, upregulation of H2 receptors, and/or second-messenger events at the parietal cell as the mechanism for the enhanced gastric secretory response.
Topics: Animals; Carbachol; Enterochromaffin Cells; Female; Gastric Acid; Gastric Mucosa; Histamine; Hyperplasia; Indomethacin; Pentagastrin; Pyrrolidonecarboxylic Acid; Ranitidine; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological; Thyrotropin-Releasing Hormone
PubMed: 9068983
DOI: 10.1016/s0306-3623(96)00296-0 -
Orvosi Hetilap Dec 1953
Topics: Carcinoid Tumor; Chromaffin System; Enterochromaffin Cells; Hematopoietic System; Humans; Intestine, Small; Neoplasms
PubMed: 13145207
DOI: No ID Found -
Surgery Dec 1985To evaluate the responsiveness of isolated, hyperplastic antral gastrin-producing G cells to a variety of secretagogues, hyperplastic hypergastrinemia was produced in...
To evaluate the responsiveness of isolated, hyperplastic antral gastrin-producing G cells to a variety of secretagogues, hyperplastic hypergastrinemia was produced in Sprague-Dawley rats by fundusectomy. Mean serum immunoreactive gastrin (IRG) concentration was elevated fivefold above controls 4 days after operation and rose steadily to an eightfold increase at 66 days. Mean antral G cell density remained at control levels for as long as 7 days, increased twofold at 14 days, then remained between twofold and threefold greater than controls for as long as 66 days after operation. Antral mucosa IRG content increased from 141 +/- 38 (control) to 262 +/- 58 ng IRG/gm mucosa (4 to 6 weeks after fundusectomy). Crude fractions of dispersed antral mucosa cells enriched in G cells from fundusectomized rats contained 6.5% +/- 1.4% G cells with 0.19 +/- 0.6 pg IRG/G cell. Corresponding preparations from nonoperated rats contained 5.1% +/- 0.5% G cells with 0.07 +/- 0.02 pg IRG/G cell. Viability averaged greater than 95% for all preparations. Gastrin secretion was monitored in cell preparations further enriched in G cells (9% to 10%) by Percoll density gradient centrifugation either in the absence (basal) or presence of bombesin (1 mumol, 1 nmol/L), carbachol (1 mmol/L), leucine (10 mmol/L), and ethylamine (10 mmol/L). The basal secretory rate of hyperplastic G cell populations averaged 250% greater than normal G cell basal rates. Hyperplastic G cell preparations had an increased IRG secretory rate in the presence of bombesin (1 mumol/L, 750%; 1 nmol/L, 191%), leucine (120%), ethylamine (236%), and carbachol (183%). These conditions failed to increase the IRG secretory rate above basal in preparations from normal antra. Viable, dispersed, hyperplastic G cells have increased IRG content and basal IRG secretory rate and are functionally responsive to a variety of secretagogues.
Topics: Animals; Centrifugation, Density Gradient; Chromaffin System; Enterochromaffin Cells; Fluorescent Antibody Technique; Gastric Fundus; Gastric Mucosa; Gastrins; Histocytochemistry; Hyperplasia; Immunoenzyme Techniques; In Vitro Techniques; Laparotomy; Male; Pyloric Antrum; Radioimmunoassay; Rats; Rats, Inbred Strains
PubMed: 3906974
DOI: No ID Found