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The Journal of Physiology Jan 2017
Topics: Enterochromaffin Cells; Ion Transport; Serotonin
PubMed: 28035678
DOI: 10.1113/JP273041 -
The American Journal of Chinese Medicine 1980Guinea pig acupuncture points located on the back of the animal, cranial and caudal to the last rib in the muscular groove between longissimus dorsi and iliocostalis,...
Guinea pig acupuncture points located on the back of the animal, cranial and caudal to the last rib in the muscular groove between longissimus dorsi and iliocostalis, were treated by electro-acupuncture (EA). In the duodenum, when compared with the control, the EA-treated group showed a significant decrease of its enterochromaffin (EC) cell count. However, the sham-treated group also had a lower EC cell count compared to the control. Decreased EC counts were also observed in the jejunum and colon in both EA and sham treated groups; however, they were not significant except in the sham-treated colon. The present study demonstrated that in the normal guinea pigs electro-acupuncture on certain points tends to cause a decrease of the EC cell count in some parts of the gut; however, such results cannot be completely attributed to the effect of acupuncture.
Topics: Acupuncture Therapy; Animals; Cell Count; Chromaffin System; Electric Stimulation; Enterochromaffin Cells; Guinea Pigs; Intestines; Male
PubMed: 7211748
DOI: 10.1142/s0192415x80000268 -
Arkhiv Anatomii, Gistologii I... Sep 1985The modern classification of the gastroenteropancreatic endocrine system (GEPES) is presented. Qualitative and quantitative composition of the entero-endocrine system... (Review)
Review
The modern classification of the gastroenteropancreatic endocrine system (GEPES) is presented. Qualitative and quantitative composition of the entero-endocrine system (EES) included in the GEPES is considered, as well as functional role of every type of the cells. The literature data are summarized and the morphology at the light optic and electron microscopic levels of the endocrine cells and the peptidergic nerves of the intestine is demonstrated. The existing methods for investigation of the EES endocrine cells and for the whole neuroendocrine complex of the gastro-intestinal tract taken together are analysed.
Topics: APUD Cells; Animals; Chromaffin System; Digestive System; Enterochromaffin Cells; Gastric Mucosa; Gastrointestinal Hormones; Histocytochemistry; Immunochemistry; Intestinal Mucosa; Microscopy, Electron; Neurosecretory Systems; Pancreas; Peptides; Phosphopyruvate Hydratase; Rats; Substance P; Vasoactive Intestinal Peptide
PubMed: 2415089
DOI: No ID Found -
Uspekhi Sovremennoi Biologii 1975
Review
Topics: Animals; Blood Coagulation; Blood Pressure; Carcinoid Tumor; Chromaffin System; Duodenal Ulcer; Enterochromaffin Cells; Ganglia, Autonomic; Histocytochemistry; Humans; Intestinal Mucosa; Melatonin; Mesoderm; Neoplasms; Respiration; Serotonin; Stomach Ulcer
PubMed: 1103502
DOI: No ID Found -
Physiological Reports Mar 2017Enterochromaffin (EC) cells located in the gastrointestinal (GI) tract provide the vast majority of serotonin (5-HT) in the body and constitute half of all...
Enterochromaffin (EC) cells located in the gastrointestinal (GI) tract provide the vast majority of serotonin (5-HT) in the body and constitute half of all enteroendocrine cells. EC cells respond to an array of stimuli, including various ingested nutrients. Ensuing 5-HT release from these cells plays a diverse role in regulating gut motility as well as other important responses to nutrient ingestion such as glucose absorption and fluid balance. Recent data also highlight the role of peripheral 5-HT in various pathways related to metabolic control. Details related to the manner by which EC cells respond to ingested nutrients are scarce and as that the nutrient environment changes along the length of the gut, it is unknown whether the response of EC cells to nutrients is dependent on their GI location. The aim of the present study was to identify whether regional differences in nutrient sensing capability exist in mouse EC cells. We isolated mouse EC cells from duodenum and colon to demonstrate differential responses to sugars depending on location. Measurements of intracellular calcium concentration and 5-HT secretion demonstrated that colonic EC cells are more sensitive to glucose, while duodenal EC cells are more sensitive to fructose and sucrose. Short-chain fatty acids (SCFAs), which are predominantly synthesized by intestinal bacteria, have been previously associated with an increase in circulating 5-HT; however, we find that SCFAs do not acutely stimulate EC cell 5-HT release. Thus, we highlight that EC cell physiology is dictated by regional location within the GI tract, and identify differences in the regional responsiveness of EC cells to dietary sugars.
Topics: Animals; Calcium; Colon; Duodenum; Enterochromaffin Cells; Fatty Acids, Volatile; Fructose; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Serotonin; Sucrose
PubMed: 28320893
DOI: 10.14814/phy2.13199 -
APMIS : Acta Pathologica,... May 1996Thirty patients with chronic renal failure (CRF) and 30 age- and sex-matched controls were assessed for gastrointestinal diseases by gastroscopy, serum gastrin...
Thirty patients with chronic renal failure (CRF) and 30 age- and sex-matched controls were assessed for gastrointestinal diseases by gastroscopy, serum gastrin determination, and routine clinical and laboratory evaluation. Biopsy specimens from their gastric oxyntic mucosa were immunohistochemically stained with monoclonal antibodies against serotonin (5-hydroxytryptamine) and chromogranin A, the latter staining all gastric endocrine cells, the former disclosing serotonin-containing enterochromaffin (EC) cells only. The average EC cell density (cells/mm2) in the CRF patients was significantly lower than in the controls: 2.6 vs 12.9 (p = 0.0005). The EC cell counts also correlated negatively with serum gastrin values (p = 0.0031). The densities of the chromogranin-positive cells did not differ between CRF patients (74 cells/mm2) and controls (76 cells/mm2) (p = 0.7559). We conclude that, in addition to the previously known findings of hypoacidity, persistent hypergastrinaemia, and G and parietal cell hyperplasia, CRF also reduces the number of oxyntic EC cells. The negative correlation between EC cell density and serum gastrin levels reflects the complex interplay between different endocrinological activities in the gastrointestinal tract.
Topics: Adult; Cell Count; Enterochromaffin Cells; Female; Gastric Mucosa; Humans; Kidney Failure, Chronic; Male; Middle Aged
PubMed: 8703442
DOI: 10.1111/j.1699-0463.1996.tb00728.x -
American Journal of Physiology.... Nov 2006Although 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...
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.
Topics: Acetylcholine; Acridine Orange; Animals; Cell Separation; Centrifugation, Density Gradient; Cyclic AMP; Enterochromaffin Cells; Flow Cytometry; Ileum; Immunohistochemistry; Murinae; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Reverse Transcriptase Polymerase Chain Reaction; Serotonin; Tryptophan Hydroxylase; gamma-Aminobutyric Acid
PubMed: 16455786
DOI: 10.1152/ajpgi.00552.2005 -
The American Journal of Physiology Nov 1999Enterochromaffin-like (ECL) cells play a pivotal role in the peripheral regulation of gastric acid secretion as they respond to the functionally important... (Review)
Review
Enterochromaffin-like (ECL) cells play a pivotal role in the peripheral regulation of gastric acid secretion as they respond to the functionally important gastrointestinal hormones gastrin and somatostatin and neural mediators such as pituitary adenylate cyclase-activating peptide and galanin. Gastrin is the key stimulus of histamine release from ECL cells in vivo and in vitro. Voltage-gated K(+) and Ca(2+) channels have been detected on isolated ECL cells. Exocytosis of histamine following gastrin stimulation and Ca(2+) entry across the plasma membrane is catalyzed by synaptobrevin and synaptosomal-associated protein of 25 kDa, both characterized as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein. Histamine release occurs from different cellular pools: preexisting vacuolar histamine immediately released by Ca(2+) entry or newly synthesized histamine following induction of histidine decarboxylase (HDC) by gastrin stimulation. Histamine is synthesized by cytoplasmic HDC and accumulated in secretory vesicles by proton-histamine countertransport via the vesicular monoamine transporter subtype 2 (VMAT-2). The promoter region of HDC contains Ca(2+)-, cAMP-, and protein kinase C-responsive elements. The gene promoter for VMAT-2, however, lacks TATA boxes but contains regulatory elements for the hormones glucagon and somatostatin. Histamine secretion from ECL cells is thereby under a complex regulation of hormonal signals and can be targeted at several steps during the process of exocytosis.
Topics: Enterochromaffin Cells; Exocytosis; Gastric Mucosa; Histamine Release
PubMed: 10564076
DOI: 10.1152/ajpcell.1999.277.5.C845 -
American Journal of Physiology.... Feb 2019The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine...
The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine (ACh), presumably via histamine 4 receptors, and weakly activated by histamine alone. Sensing these signals, enterochromaffin cells could participate in intestinal intolerance or allergic reactions to food constituents associated with elevated histamine levels. In this study we aimed to analyze the underlying molecular mechanisms. Inhibition by mepyramine and mibefradil indicated that histamine alone caused a rise in intracellular calcium concentration ([Ca]) via histamine 1 receptors involving T-type voltage-gated calcium channels (VGCCs). Sensitivity to histamine was enhanced by pretreatment with the inflammatory cytokine tumor necrosis factor-α (TNF-α). In accordance with the relief it offers some inflammatory bowel disease patients, otilonium bromide, a gut-impermeable inhibitor of T-type (and L-type) VGCCs and muscarinic ACh receptors, efficiently inhibited the [Ca] responses induced by histamine plus ACh or by histamine alone in P-STS cells. It will take clinical studies to show whether otilonium bromide has promise for the treatment of adverse food reactions. The cells did not react to the nutrient constituents glutamate, capsaicin, cinnamaldehyde, or amylase-trypsin inhibitors and the transient receptor potential channel vanilloid 4 agonist GSK-1016790A. The bacterial product butyrate evoked a rise in [Ca] only when added together with ACh. Lipopolysaccharide had no effect on [Ca] despite the presence of Toll-like receptor 4 protein. Our results indicate that inflammatory conditions with elevated levels of TNF-α might enhance histamine-induced serotonin release from intestinal neuroendocrine cells. NEW & NOTEWORTHY We show that histamine synergistically enhances the intracellular calcium response to the physiological agonist acetylcholine in human ileal enterochromaffin tumor cells. This synergistic activation and cell activation by histamine alone largely depend on T-type voltage-gated calcium channels and are inhibited by the antispasmodic otilonium bromide. The cells showed no response to wheat amylase-trypsin inhibitors, suggesting that enterochromaffin cells are not directly involved in nongluten wheat sensitivity.
Topics: Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Enterochromaffin Cells; Histamine; Humans; Membrane Potentials
PubMed: 30540489
DOI: 10.1152/ajpgi.00261.2018 -
Gastroenterology Aug 1993In vivo studies have suggested an important role for gastric enterochromaffinlike (ECL) cells in mediating acid secretion. Direct evidence for this function is lacking...
BACKGROUND
In vivo studies have suggested an important role for gastric enterochromaffinlike (ECL) cells in mediating acid secretion. Direct evidence for this function is lacking and requires a preparation of highly purified ECL cells. This work investigates the possible role and mechanism of histamine release from the ECL cell in the peripheral regulation of acid secretion, using purified ECL cells from rat fundic mucosa.
METHODS
A combination of elutriation and density-gradient centrifugation was used to purify rat fundic ECL cells. Enrichment was determined by the presence of acidic vacuoles containing a V type adenosine triphosphatase, electron microscopy, immunostaining, and histamine content and release.
RESULTS
ECL cells were enriched at least 65-fold with respect to the fundic epithelium. Gastrin (EC50 0.2 nmol/L) and cholecystokinin octapeptide (nonsulfated, EC50 0.04 nmol/L) stimulated histamine release in a time- and dose-dependent manner, suggesting a CCK-B receptor subtype, confirmed by the inhibition of gastrin/CCK stimulation with the CCK-B antagonist L365,260. Somatostatin also inhibited gastrin-mediated histamine release. Single cell imaging showed that gastrin elevated intracellular cytosolic calcium concentration biphasically. Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release. Epinephrine (blocked by propranolol), forskolin, and dibutyryl-5'-cyclic adenosine monophosphate were also effective, implicating a beta-adrenergic pathway. The H3 agonist R-alpha-methyl-histamine inhibited, whereas the H3-antagonist thioperamide potentiated gastrin/CCK stimulated histamine release.
CONCLUSIONS
These in vitro results support a central role for the ECL cell in the peripheral regulation of gastric acid secretion.
Topics: Animals; Calcium; Enterochromaffin Cells; Female; Gastrins; Histamine Release; Immunohistochemistry; Intracellular Membranes; Microscopy, Electron; Microscopy, Fluorescence; Rats; Rats, Sprague-Dawley; Receptors, Histamine; Sincalide; Somatostatin; Stimulation, Chemical
PubMed: 7687574
DOI: 10.1016/0016-5085(93)90719-s