Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The mechanism of histamine secretion from gastric enterochromaffin-like cells. 1090 56

Conventional intracellular microelectrodes and marker injection techniques were used to study the actions of histamine on inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine. Bath application of histamine (1-300 microM) reversibly suppressed both noradrenergic and non-adrenergic slow inhibitory postsynaptic potentials in a concentration-dependent manner. These effects of histamine were mimicked by the selective histamine H(3) receptor agonist R(-)-alpha-methylhistamine but not the selective histamine H(1) receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT dimaleate), or the selective histamine H(2) receptor agonist, dimaprit. The histamine H(3) receptor antagonist, thioperamide, blocked the effects of histamine. Histamine H(1) and H(2) receptor antagonists did not change the action of histamine. Hyperpolarizing responses to focal application of norepinephrine or somatostatin by pressure ejection from micropipettes were unaffected by histamine and R(-)-alpha-methylhistamine. The results suggest that histamine acts at presynaptic histamine H(3) receptors on the terminals of sympathetic postganglionic fibers and intrinsic somatostatinergic nerves in the small intestine to suppress the release of the inhibitory neurotransmitters, norepinephrine and somatostatin.
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PMID:Histamine H3 receptor-mediated suppression of inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine. 1084 98

The ligands interacting with enterochromaffin-like (ECL) and parietal cells and the signaling interactions between these cells were investigated in rabbit gastric glands using confocal microscopy. Intracellular calcium concentration ([Ca(2+)](i)) changes were used to monitor cellular responses. Histamine and carbachol increased [Ca(2+)](i) in parietal cells. Gastrin (1 nM) increased [Ca(2+)](i) in ECL cells and adjacent parietal cells. Only the increase of [Ca(2+)](i) in parietal cells was inhibited by H(2) receptor antagonists (H(2)RA). Gastrin (10 nM) evoked an H(2)RA-insensitive [Ca(2+)](i) increase in parietal cells. Carbachol produced large H(2)RA- and somatostatin-insensitive signals in parietal cells. Pituitary adenylate cyclase-activating peptide (PACAP, 100 nM) elevated [Ca(2+)](i) in ECL cells and adjacent parietal cells. H(2)RAs abolished the PACAP-stimulated [Ca(2+)](i) increase in adjacent parietal cells. Somatostatin did not inhibit the increase of [Ca(2+)](i) in parietal cells stimulated with histamine, high gastrin concentrations, or carbachol but abolished ECL cell calcium responses to gastrin or PACAP. Hence, rabbit parietal cells express histaminergic, muscarinic, and CCK-B receptors coupled to calcium signaling but insensitive to somatostatin, whereas rabbit and rat ECL cells express PACAP and CCK-B calcium coupled receptors sensitive to somatostatin.
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PMID:Regulation of parietal cell calcium signaling in gastric glands. 1105 3

Acid secretion first appears in the stomach during the later stages of fetal development. Gastric acid secretion is regulated by the stimulatory effects of gastrin, histamine, acetylcholine and the inhibitory actions of somatostatin on their respective receptors. A semi-quantitative reverse transcriptase-polymerase chain reaction method for the determination of changes in mRNA expression for these receptors was developed and correlated with known changes in gastric acidity. Glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) was used as a reference and an internal standard. The antrum and fundus from four age groups were assayed: 80 days of gestation, 110 days of gestation, term (145 days) and adult animals. The CCK B/gastrin and the histamine (H(2)) receptor mRNA were significantly lower in samples from the fundus of fetuses, from 80 and 110 days of gestation when compared with the adult fundus. Histamine receptor mRNA in the antrum was also significantly lower in the 80 and 110 days of gestation samples relative to the term fetal antrum. Somatostatin II receptor mRNA levels in the antrum decreased with increasing age with no change in the fundus. These findings suggest that changes in receptor gene expression, may be responsible for the diminished gastric acidity and responsiveness observed in the fetal stomach.
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PMID:Expression of receptors regulating gastric acidity in the developing sheep stomach. 1149 84

The regulation of acid secretion in the stomach involves a complex network of factors that stimulate secretion in response to the ingestion of a meal and maintain homeostasis of gastric pH. Genetically engineered mouse models have provided a new opportunity to investigate the importance and function of specific molecules and pathways involved in the regulation of acid secretion. Mouse mutants with disruptions in the three major stimulatory pathways for acid secretion in parietal cells, gastrin, histamine, and acetylcholine, have been generated. Disruption of the gastrin pathway results in a major impairment in both basal and induced acid secretion. Histamine and acetylcholine pathway mutants also have significant alterations in acid secretion, although the impairment does not appear to be as severe as in gastrin pathway mutants, perhaps due in part to the hypergastrinemia that occurs. Mice with a disruption in the somatostatin pathway have increased gastric acid secretion, which confirms an important negative regulatory role for this factor. This review discusses these genetically engineered mouse models, as well as others, that provide insight into the complex regulation of in vivo gastric acid secretion. The regulation of growth and cellular morphology of the stomach in these mouse models is also presented. In addition, transgene promoters that are expressed in the gastric epithelium are discussed because these promoters will be important tools to alter cellular physiology in new mouse models in the future.
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PMID:Insights into the regulation of gastric acid secretion through analysis of genetically engineered mice. 1251 96

Rat stomach ECL cells release histamine in response to gastrin. Submucosal microinfusion of endothelin or adrenaline, known to cause vasoconstriction and gastric lesions, mobilized striking amounts of histamine. While the histamine response to gastrin is sustainable for hours, that to endothelin and adrenaline was characteristically short-lasting (1-2 h). The aims of this study were to identify the cellular source of histamine mobilized by endothelin and adrenaline, and examine the differences between the histamine-mobilizing effects of gastrin, and of endothelin and adrenaline. Endothelin, adrenaline or gastrin were administered by submucosal microinfusion. Gastric histamine mobilization was monitored by microdialysis. Local pretreatment with the H1-receptor antagonist mepyramine and the H2-receptor antagonist ranitidine did not prevent endothelin- or adrenaline-induced mucosal damage. Submucosal microinfusion of histamine did not cause damage. Acid blockade by ranitidine or omeprazole prevented the damage, suggesting that acid back diffusion contributes. Gastrin raised histidine decarboxylase (HDC) activity close to the probe, without affecting the histamine concentration. Endothelin and adrenaline lowered histamine by 50-70%, without activating HDC. Histamine mobilization declined upon repeated administration. Endothelin reduced the number of histamine-immunoreactive ECL cells locally, and reduced the number of secretory vesicles. Thus, unlike gastrin, endothelin (and adrenaline) is capable of exhausting ECL-cell histamine. Microinfusion of alpha-fluoromethylhistidine (known to deplete ECL cells but not mast cells of histamine) reduced the histamine-mobilizing effect of endothelin by 80%, while 1-week pretreatment with omeprazole enhanced it, supporting the involvement of ECL cells. Somatostatin or the prostanoid misoprostol inhibited gastrin-, but not endothelin-stimulated histamine release, suggesting that endothelin and gastrin mobilize histamine via different mechanisms. While gastrin effectively mobilized histamine from ECL cells in primary culture, endothelin had no effect, and adrenaline, a modest effect. Hence, the striking effects of endothelin and adrenaline on ECL cells in situ are probably indirect, possibly a consequence of ischemia.
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PMID:Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study. 1450 42

Gastric acid secretion is regulated by the stimulatory effects of gastrin, histamine and acetylcholine and the inhibitory actions of somatostatin on their respective receptors. We proposed that the expression of these receptors could be regulated at the transcription level by agonists and antagonists known to effect acid secretion. A quantitative "real-time" PCR method was used to determine changes in mRNA expression for these receptors. The agonists, pentagastrin and histamine, and the H2 antagonist, ranitidine, were infused over a 6 h period to conscious sheep. Blood, antral and fundic tissue samples were taken for analysis. Both pentagastrin and histamine resulted in elevated plasma somatostatin concentrations during the treatment. Ranitidine stimulated a fourfold increase in plasma gastrin while histamine caused a transient decrease. Except for an increase in antral gastrin following ranitidine infusion, there was no significant change in gastric gastrin and somatostatin concentration. Histamine (H2) receptor mRNA expression in the antrum was significantly increased by pentagastrin and decreased by ranitidine. Pentagastrin also stimulated a significant increase in the level of muscarinic (M3) receptor mRNA in the antrum. Antral somatostatin II receptor mRNA was significantly decreased by histamine. In the fundus, pentagastrin infusion resulted in a significant increase in histamine receptor mRNA and a decrease in the muscarinic receptor mRNA. This work demonstrates that the receptors involved in the regulation of acid secretion can be regulated by local events.
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PMID:Regulation of expression of the receptors controlling gastric acidity. 1525 67

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK(2) receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H(2) receptors on the parietal cells, resulting in acid secretion. The parietal cells express H(2), M(3), and CCK(2) receptors and somatostatin sst(2) receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK(2) receptor genes) and genes that are important for "cross-talk" between H(2) receptors and other receptors on the parietal cell (CCK(2), M(3), and sst(2) receptors). Such analysis may provide insight into the functional significance of gastric histamine.
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PMID:Differentiation of the gastric mucosa. I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes. 1695 53

This paper summarizes important developments, published over the past year, that improve our understanding of the regulation of gastric acid secretion at the central, peripheral, and intracellular levels and mechanisms by which various neurotransmitters, paracrine agents, and hormones regulate gastric secretion and are themselves regulated. The main stimulants of acid secretion from the parietal cell are histamine, gastrin, and acetylcholine. Histamine, released from fundic enterochromaffin-like cells, interacts with H(2) receptors on parietal cells that are coupled via separate G proteins to activation of adenylate cyclase and phospholipase C. The antral hormone gastrin, released by activation of cholinergic and bombesin/gastrin-releasing peptide neurons, acts mainly by release of histamine from enterochromaffin-like cells. Acetylcholine, released from gastric intramural neurons, interacts with muscarinic M(3) receptors on parietal cells and has little, if any, effect on histamine secretion. The main inhibitor of acid secretion is somatostatin, which, acting via sst(2) receptors, exerts a tonic restraint on parietal, enterochromaffin-like, and gastrin cells. In patients with duodenal ulcer, infection with Helicobacter pylori is associated with increased basal and stimulated plasma gastrin concentrations and acid outputs. The precise mechanisms mediating the effects are not known, but evidence suggests that both products of the bacteria and the inflammatory infiltrate are capable of stimulating gastrin and acid secretion.
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PMID:Regulation of gastric acid secretion. 1702 91

This article summarizes data published during the past year that improve our understanding of the mechanisms by which various neurotransmitters, paracrine agents, and hormones regulate gastric acid secretion and are themselves regulated. The main stimulants of acid secretion are histamine, gastrin, and acetylcholine. The main inhibitor is somatostatin, which exerts a tonic restraint on parietal, enterochromaffin-like (ECL), and gastrin cells. Histamine, released from ECL cells, stimulates the parietal cell directly via H(2) receptors and indirectly via H(3) receptors coupled to inhibition of somatostatin secretion. Gastrin, acting via gastrin/cholecystokinin-B (CCK-B), now termed CCK(2), receptors on ECL cells activates histidine decarboxylase, releases histamine, and induces ECL hypertrophy and hyperplasia. The latter might be responsible for the rebound hyperacidity observed after withdrawal of long-term antisecretory therapy. The neurotransmitter pituitary adenylate cyclase-activating polypeptide stimulates histamine secretion from isolated ECL cells, but its physiologic role, if any, is not known. Acetylcholine, released from gastric postganglionic intramural neurons, stimulates the parietal cell directly via muscarinic M(3) receptors and indirectly by inhibiting somatostatin secretion. Although infection with H. pylori is associated with increased basal and stimulated acid outputs in patients with duodenal ulcer, most people infected with the organism are asymptomatic and have pangastritis with decreased acid output. In the latter, eradication of the bacterium leads to an increase in gastric acidity and is associated with a two-to threefold increase in gastroesophageal reflux.
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PMID:Gastric secretion. 1703 Nov 23


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