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The American Journal of Surgical... 1995The enterochromaffin-like (ECL) cell of the oxyntic, acid-secreting mucosa is at present the most extensively studied endocrine cell type in the gastrointestinal tract.... (Review)
Review
The enterochromaffin-like (ECL) cell of the oxyntic, acid-secreting mucosa is at present the most extensively studied endocrine cell type in the gastrointestinal tract. It is functionally related to acid secretion through paracrine release of histamine. Its ability to undergo proliferation in response to the trophic stimulus of hypergastrinemia has important implications in pathology, being involved in the development of ECL-cell carcinoid tumors of rodents treated with powerful inhibitors of acid secretion as well as in that of most human gastric carcinoids which, with rare exceptions, are composed of ECL cells. The various aspects of the ECL-cell response to hypergastrinemia in humans are discussed in this review. The trophic effect of gastrin is specific for ECL cells and its sensitivity is enhanced by the female sex and by the genetic background of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Exposure of ECL cells to hypergastrinemia induces peculiar changes in the structure of cytoplasmic granules and triggers the phenotypic expression of a novel protein, the alpha subunit of glycoprotein hormones, absent in normal cells. The ECL-cell hyperplasia driven by hypergastrinemia may influence the hypersecretory gastric state of patients with Zollinger-Ellison syndrome (ZES) by inappropriate intramucosal secretion of histamine and may contribute to the high circulating levels of basic fibroblast growth factor (bFGF), an ECL-cell product responsible for parathyroid mitogenic effects in MEN-1 patients. However, hypergastrinemia per se cannot promote evolution of hyperplasia into carcinoid tumors, for which additional unknown factors, particularly associated with atrophic gastritis or MEN-1 syndrome, are required. ECL-cell carcinoids developing within these backgrounds have a strikingly more favorable course than their gastrin-independent counterpart. Suppression of hypergastrinemia, either by antrectomy or treatment with somatostatin analogues, may induce regression of both ECL-cell hyperplasia and gastrin-sensitive ECL-cell carcinoids.
Topics: Carcinoid Tumor; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Hyperplasia; Stomach Neoplasms; Zollinger-Ellison Syndrome
PubMed: 7762739
DOI: No ID Found -
Journal of Visualized Experiments : JoVE Sep 2018Enterochromaffin (EC) cells in the gastrointestinal (GI) epithelium constitute the largest subpopulation of enteroendocrine cells. As specialized sensory cells, EC cells...
Enterochromaffin (EC) cells in the gastrointestinal (GI) epithelium constitute the largest subpopulation of enteroendocrine cells. As specialized sensory cells, EC cells sense luminal stimuli and convert them into serotonin (5-hyroxytryptamine, 5-HT) release events. However, the electrophysiology of these cells is poorly understood because they are difficult to culture and to identify. The method presented in this paper outlines primary EC cell cultures optimized for single cell electrophysiology. This protocol utilizes a transgenic cyan fluorescent protein (CFP) reporter to identify mouse EC cells in mixed primary cultures, advancing the approach to obtaining high-quality recordings of whole cell electrophysiology in voltage- and current-clamp modes.
Topics: Animals; Cells, Cultured; Electrophysiological Phenomena; Enterochromaffin Cells; Mice
PubMed: 30320764
DOI: 10.3791/58112 -
Trends in Pharmacological Sciences Jun 2018The first step in serotonin (5-HT) biosynthesis is catalyzed by tryptophan hydroxylase (TPH). There are two independent sources of the monoamine that have distinct... (Review)
Review
The first step in serotonin (5-HT) biosynthesis is catalyzed by tryptophan hydroxylase (TPH). There are two independent sources of the monoamine that have distinct functions: first, the TPH1-expressing enterochromaffin cells (ECs) of the gut; second, TPH2-expressing serotonergic neurons. TPH1-deficient mice revealed that peripheral 5-HT plays important roles in platelet function and in inflammatory and fibrotic diseases of gut, pancreas, lung, and liver. Therefore, TPH inhibitors were developed which cannot pass the blood-brain barrier to specifically block peripheral 5-HT synthesis. They showed therapeutic efficacy in several rodent disease models, and telotristat ethyl is the first TPH inhibitor to be approved for the treatment of carcinoid syndrome. We review this development and discuss further therapeutic options for these compounds.
Topics: Animals; Disease Models, Animal; Drug Design; Enterochromaffin Cells; Enzyme Inhibitors; Humans; Molecular Targeted Therapy; Serotonin; Tryptophan Hydroxylase
PubMed: 29628275
DOI: 10.1016/j.tips.2018.03.004 -
The Yale Journal of Biology and Medicine 1992The significance of the enterochromaffin-like (ECL) cell as a critical endocrine regulator of gastric fundic mucosal function has only recently been recognized. Although... (Review)
Review
The significance of the enterochromaffin-like (ECL) cell as a critical endocrine regulator of gastric fundic mucosal function has only recently been recognized. Although the percentage of these cells present in the human fundic mucosa is less than that in rodents, the observation that they secrete histamine and are probably important modulators of parietal cell function has resulted in their attaining some considerable biological significance. The further identification of gastrin and somatostatin receptors on the surface of the ECL cells has suggested that other neurohormonal influences may be significant in the regulation of parietal cell function, utilizing the ECL cell as an intermediate modifier. While abnormalities of ECL cells in the human stomach (hyperplasia/neoplasia) have been mostly confined to observations in patients with pernicious anemia and atrophic gastritis, the recent recognition of hyperplasia in pharmacotherapeutically induced achlorhydric or hypochlorhydric states has excited considerable interest. It has been proposed that the generation of luminal hypo- or achlorhydria by powerful acid inhibitory pharmacotherapy may result in hypergastrinemia. This condition is responsible initially for the development of hyperplasia and, subsequently, possibly even neoplasia of the ECL system of the fundic mucosa. This phenomenon seems to be prevalent in rodents but has so far been only rarely observed in humans, e.g., pernicious anemia, atrophic gastritis. In particular, patients with the gastrinoma component of the multiple endocrine neoplasia type I syndrome exhibit ECL-cell hyperplasia and neoplasia after exposure to acid inhibitory pharmacotherapy. It is therefore likely that an underlying genomic phenomenon is necessary prior to the induction of hyperplasia and subsequent neoplastic transformation. The scientific evaluation of the relationship between gastrin, ECL-cell function, and the development of hyperplasia and neoplasia may provide some important information in regard to the molecular evolution of gastrointestinal neuroendocrine disease states. It is possible that the future pharmacotherapy of acid secretory disease may require regulation not only of parietal cell but of ECL-cell function.
Topics: Enterochromaffin Cells; Humans
PubMed: 1341078
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics 1993In both rodents and humans the development of gastrin-promoted gastric argyrophil enterochromaffin-like cell carcinoids requires the involvement of a genetic factor... (Review)
Review
In both rodents and humans the development of gastrin-promoted gastric argyrophil enterochromaffin-like cell carcinoids requires the involvement of a genetic factor inherent to multiple endocrine neoplasia syndrome or of type A autoimmune chronic atrophic gastritis. Prolonged severe hypergastrinaemia acting on non-gastritic mucosa, as in Zollinger-Ellison syndrome patients, results in diffuse argyrophil enterochromaffin-like cell hyperplasia but, as a rule, does not produce tumours. Combination of chronic atrophic gastritis (mostly related to Helicobacter pylori infection) with hypergastrinaemia frequently causes linear and micronodular hyperplasia of argyrophil cells, whereas carcinoids are exceptional. No tumours or pre-neoplastic lesions have been observed in patients treated long-term with proton pump inhibitors, apart from rare cases in patients with combined Zollinger-Ellison and multiple endocrine neoplasia syndromes. A moderate increase in the incidence of argyrophil cell clustering, with or without hyperplasia, probably results from the parallel evolution of ulcer-associated Helicobacter gastritis into chronic atrophic gastritis. Eradication of H. pylori with a combination of proton pump inhibitors and antibiotics suppresses gastritis and prevents ulcer recurrence.
Topics: Animals; Carcinoid Tumor; Cell Division; Enterochromaffin Cells; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pumps; Stomach Neoplasms
PubMed: 8490076
DOI: 10.1111/j.1365-2036.1993.tb00584.x -
The Histochemical Journal Aug 1987On the basis of staining results in closely related semi-thin sections from rat antral mucosa immunostained with polyclonal serotonin antibodies and silver-stained for...
On the basis of staining results in closely related semi-thin sections from rat antral mucosa immunostained with polyclonal serotonin antibodies and silver-stained for the argentaffin reaction, respectively, three different cell populations could be distinguished. One of these cell populations showed both serotonin immunoreactivity and an argentaffin reaction, a second one serotonin immunoreactivity alone, and a third one only an argentaffin reaction. These cell populations were studied electron microscopically in ultra-thin sections located between the stained semi-thin sections. The cell population displaying an agentaffin reaction and serotonin immunoreactivity showed secretory granules of the enterochromaffin cell type. A similar granular appearance was observed in cells which only exhibited an argentaffin reaction. Serotonin immunoreactivity in the absence of an argentaffin reaction was evident in some G (gastrin) cells, and in some D1 and possibly also some D (somatostatin) cells; but not all the endocrine cells of the non-enterochromaffin type displayed serotonin immunoreactivity. The significance of the different reactions in the three cell populations is discussed.
Topics: Animals; Chromaffin System; Endocrine Glands; Enterochromaffin Cells; Gastric Mucosa; Male; Microscopy, Electron; Rats; Rats, Inbred Strains
PubMed: 3429259
DOI: 10.1007/BF01675756 -
International Journal of Molecular... Aug 2021The monoamine serotonin, 5-hydroxytryptamine (5-HT), is a remarkable molecule with conserved production in prokaryotes and eukaryotes and a wide range of functions. In... (Review)
Review
The monoamine serotonin, 5-hydroxytryptamine (5-HT), is a remarkable molecule with conserved production in prokaryotes and eukaryotes and a wide range of functions. In the gastrointestinal tract, enterochromaffin cells are the most important source for 5-HT production. Some intestinal bacterial species are also able to produce 5-HT. Besides its role as a neurotransmitter, 5-HT acts on immune cells to regulate their activation. Several lines of evidence indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. In this review, we discuss the current knowledge on the production, secretion, and signaling of 5-HT in the intestine. We present an inventory of intestinal immune and epithelial cells that respond to 5-HT and describe the effects of these signaling processes on intestinal homeostasis. Further, we detail the mechanisms by which 5-HT could affect inflammatory bowel disease course and describe the effects of interventions that target intestinal 5-HT signaling.
Topics: Animals; Colitis; Enterochromaffin Cells; Epithelial Cells; Gastrointestinal Tract; Homeostasis; Humans; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Serotonin; Signal Transduction
PubMed: 34502396
DOI: 10.3390/ijms22179487 -
Acta Oncologica (Stockholm, Sweden) 1991During the last few years the endocrine stomach has come into focus much due to the side-effects produced by powerful acid blockers. A sustained and marked inhibition of... (Review)
Review
During the last few years the endocrine stomach has come into focus much due to the side-effects produced by powerful acid blockers. A sustained and marked inhibition of acid secretion in the rat results in hypergastrinemia, with gastrin cell hyperplasia, and a consequent hyperplasia of the ECL cells. This response of the ECL cells was predictable in view of previous observations that sustained hypergastrinemia causes ECL cell hyperplasia. While the gastrin cell hyperplasia levels off at about twice the normal cell density a few weeks after start of treatment, the ECL cells continue to proliferate for months to reach a five-fold higher density than normally. Evidence is accumulating that ECL cells proliferate through self replication. After life-long inhibition of acid production (high doses of ranitidine or omeprazole) or after extirpation of 75% of the acid-producing part of the stomach, ECL cell carcinoids develop. Endocrine cells in the gut often contain more than one putative messenger. Thus, gastrin cells in many species store GABA and peptide YY; in e.g. cat and man they store in addition a xenopsin-like peptide. Neuromedin U and pituitary adenylate cyclase activating peptide (PACAP) have recently been demonstrated in gut nerves. Their role in gut physiology remains to be identified.
Topics: Animals; Enterochromaffin Cells; Gastric Acid; Gastrins; Humans; Hyperplasia; Neuropeptides; Neurosecretory Systems; Peptide YY; Peptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Stomach; gamma-Aminobutyric Acid
PubMed: 1854499
DOI: 10.3109/02841869109092396 -
The Yale Journal of Biology and Medicine 1992Enterochromaffin-like (ECL) cells are the dominant endocrine cell type in the oxyntic mucosa. Normally regarded as histamine-producing cells, they are exquisitely... (Review)
Review
Enterochromaffin-like (ECL) cells are the dominant endocrine cell type in the oxyntic mucosa. Normally regarded as histamine-producing cells, they are exquisitely sensitive to the trophic action of gastrin and undergo a hyperplastic increase in a variety of hypergastrinemic conditions. A hyperplasia-neoplasia sequence of ECL-cell proliferations has been recently proposed, following the realization that increasingly severe degrees of ECL-cell hyperplasias over a period of several years can progress to ECL-cell carcinoids. Such carcinoids arising in patients with chronic hypergastrinemia differ both in their clinical and pathologic profiles from the sporadic carcinoids that occur in normogastrimenic individuals and, therefore, need to be distinguished from them. This distinction is particularly important for their clinical management, since antrectomy appears to be of benefit in ECL carcinoids of hypergastrinemic patients.
Topics: Animals; Cell Division; Enterochromaffin Cells; Humans; Hypertrophy
PubMed: 1341080
DOI: No ID Found -
Neurogastroenterology and Motility Apr 2004The enteric nervous system in combination with inputs from parasympathetic and sympathetic nerves regulate the contractile, secretory and vasomotor activity of the... (Review)
Review
The enteric nervous system in combination with inputs from parasympathetic and sympathetic nerves regulate the contractile, secretory and vasomotor activity of the gastrointestinal track via neural reflexes. Sensory elements which may be present in specialized neurones, enteroendocrine cells or mast cells detect changes in force, chemical composition or even foreign antigens. Sensory elements signal the enteric nervous system to correct these changes by altering contractile activity, secretion and blood flow. Advances have been made in understanding the sensory mechanisms that are involved in 5-hydroxytryptamine (5-HT) release from enterochromaffin cells (EC) or a model for EC cells. These advances relate to roles for ATP and its metabolites ADP and adenosine in mechanotransduction and a role for a sodium glucose cotransporter, a SGLT-like protein, in chemotransduction.
Topics: Animals; Digestive System; Enteric Nervous System; Enterochromaffin Cells; Gastrointestinal Motility; Humans; Mechanotransduction, Cellular; Reflex; Sensory Receptor Cells
PubMed: 15066007
DOI: 10.1111/j.1743-3150.2004.00477.x