Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study involved evaluation of the role played by cyclic AMP on the secretion and mechanism of action of gastrin in man. On the basis of the results obtained, gastrin secretion induced by an excessive rise in gastric pH is accompanied by a simultaneous increase in plasma cyclic AMP concentrations (p less than 0.05) as well as a tissue cyclic AMP in the region of the fundus (p less than 0.001). By contrast, no significant change was seen regarding antropyloric AMP. As a result, it is felt that cyclic AMP does not play a direct role in the secretion of gastrin by G cells but is a mediator of the mechanism of action of gastrin in terms of the secretion of HCl by the parietal cell.
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PMID:[Role of cyclic AMP in gastric secretion. The secretion and mechanism of action of gastrin]. 254 Nov 49

Intracellular recordings from cultured parietal cells of the rat gastric fundus showed that carbachol, pentagastrin, histamine (in the presence of isobutylmethylxanthine; IBMX) and dibutyryl cyclic AMP induced hyperpolarizing responses which were sensitive to a K+ channel blocker, quinine. The Ca2+ ionophore, ionomycin, also induced a quinine-sensitive hyperpolarization. Deprivation of extracellular Ca2+ preferentially inhibited the hyperpolarizing responses to histamine (plus IBMX) and to dibutyryl cyclic AMP. Caffeine, oxalate and dantrolene sodium, which are known to affect Ca2+ transport in the endoplasmic reticulum, selectively inhibited the carbachol response. Mitochondrial inhibitors (KCN and carbonylcyanide p-trifluoromethoxyphenylhydrazone) preferentially suppressed the gastrin response. Cytosolic Ca2+ measurements with fura-2 indicated that significant increases in the intracellular concentration of free Ca2+ were induced not only by Ca2+-mediated acid secretagogues (carbachol and gastrin), but also by a cyclic AMP-mediated secretagogue (histamine plus IBMX). Dibutyryl cyclic AMP also increased cytosolic Ca2+ ions. It is concluded that stimulation of receptors to histamine, carbachol and gastrin gives rise to mobilization of Ca2+ ions into the cytoplasm from the different sources, thereby stimulating Ca2+-activated K+ channels in cultured rat parietal cells.
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PMID:Acid secretagogues induce Ca2+ mobilization coupled to K+ conductance activation in rat parietal cells in tissue culture. 275 38

We have recently reported that bombesin (BBS)-stimulated gastrin release is principally dependent on a Ca2+/calmodulin intracellular pathway, and that it is independent of the cyclic AMP-mediated pathway. Recently it was demonstrated that stimulation of protein kinase C (PK-C) resulted in increased gastrin release from the isolated canine G-cells in cultures. The role of PK-C in the BBS-evoked gastrin release, however, remains unexamined. In this study we examined a possible role of PK-C in the secretion of BBS-stimulated gastrin from isolated perfused rat stomach. The effect of phosphorylation on gastrin release, in response to BBS, was also determined. Administration of phorbol ester (PMA 10-100 nM, a PK-C activator) alone significantly provoked gastrin release, but markedly inhibited the BBS (1 nM) stimulated gastrin secretion in a dose-dependent manner. Molybdic acid (phosphatase inhibitor), caused an enhancement of BBS-evoked gastrin response at doses of 5 or greater than 5 mM. These results suggest that: (1) diacylglycerol/PK-C pathway may exert a negative feedback control over BBS-induced gastrin release; (2) phosphorylation step is required for gastrin secretion in response to BBS.
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PMID:Role of protein kinase C and phosphorylation in bombesin-evoked gastrin release from isolated perfused rat stomach. 281 54

The diterpene, forskolin, direct activator of the catalytic subunit of the adenylate cyclase from various tissues, also stimulates gastric acid secretion: in vitro, with an isolated parietal cell preparation, forskolin dose-dependently stimulated acid secretion (EC50: 1 microM) (measured by accumulation in the acidic spaces of the weak base [14C]-aminopyrine) and the maximal acid secretory value at 0.1 mM was 4 times higher than that obtained with histamine. Forskolin dramatically increased the production of intracellular cyclic-AMP at a level 4 times higher than that obtained with histamine at the same concentration. In vivo, gastric acid secretion of the rat is dose-dependently increased. The doses required to get a significant response (100 nmol/kg) were 1,000 times higher than those required for gastrin and 100 times lower than those for histamine, but the same maximal value was obtained. Cimetidine did not significantly modified this response. These results demonstrate that, both in vitro and in vivo, forskolin is a potent stimulant for gastric acid secretion.
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PMID:[Is forskolin a stimulant of gastric secretion?]. 285 29

Organ culture was used to compare gastrin and somatostatin release from cultured antral mucosa obtained from duodenal ulcer and non-ulcer (control) subjects. In response to dibutyryl cyclic AMP (DBCAMP) cultured antral mucosal explants from patients with a history of duodenal ulcer released a greater proportion of antral gastrin into the medium than did antral mucosal explants from non-ulcer subjects. Somatostatin release from antral mucosa from duodenal ulcer patients was substantially less than somatostatin released by antral explants from non-ulcer subjects. In the non-ulcer subjects there was a direct positive correlation between the amounts of antral somatostatin and gastrin released into the culture medium (r = 0.64, less than p 0.01). In the duodenal ulcer patients, however, there was no correlation between gastrin release and somatostatin release from antral mucosa ( r = 0.09; p greater than 0.2). Results of these studies identify enhanced gastrin release in response to stimulation and decreased release of somatostatin from antral mucosa of duodenal ulcer patients. These alterations in paracrine relationships of antral somatostatin and gastrin in duodenal ulcer subjects may contribute, at least in part, to the pathogenesis of duodenal ulcer disease.
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PMID:Antral release of gastrin and somatostatin in duodenal ulcer and control subjects. 287 83

Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.
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PMID:Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995). 287 48

Bombesin, a polypeptide derived from frog skin, has been shown to stimulate gastrin release from the gastric antrum in vivo and in vitro. To elucidate the mechanisms of this effect, we developed a method to culture isolated and enriched G cells from canine stomach. After digestion of antral mucosa with collagenase and EDTA, dispersed cells were fractionated by counterflow elutriation then cultured on a collagen support. Bombesin and three molecular forms of canine gastrin-releasing peptides all stimulated gastrin release from G cells in a dose-dependent manner. The effect of bombesin was suppressed by somatostatin and potentiated by dibutyryl cyclic AMP (10(-3) M) but not by carbachol (10(-6) M). Extracellular calcium depletion attenuated the stimulation of gastrin release by bombesin but not by forskolin. These findings suggest that the bombesin family peptides directly activate G cells through calcium-dependent mechanisms to cause gastrin release.
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PMID:Stimulation of gastrin release by bombesin and canine gastrin-releasing peptides. Studies with isolated canine G cells in primary culture. 288 Aug 70

Gastric acid secretion is controlled by neurocrine, endocrine, and paracrine pathways. At the organ level, the neurocrine and endocrine systems provide long-range regulation; and near the target cell the paracrine system appears to predominate. The integration of the regulatory commands from these various pathways is complex and, as a result, some pathways have not yet been clearly defined. Present evidence suggests that acetylcholine from mucosal nerve endings acts by 2 possible pathways. It interacts with muscarinic receptors on the oxyntic cell stimulating acid production. It is also capable of releasing histamine from the paracrine cell in the gastric glands, and histamine then acts on the oxyntic cells. The endocrine effect on acid secretion mediated by gastrin is less clear. Gastrin binds to oxyntic cell plasma membranes but has little or no direct stimulatory effect on the acid-secreting cell. It is assumed that its stimulatory action on acid secretion in vivo is mediated primarily by increasing histamine levels near the oxyntic cells. Histamine, released from paracrine cells near the oxyntic cells, is probably controlled by acetylcholine and gastrin, but other mechanisms are being explored. Histamine binds to the H2-receptors on the oxyntic cell plasma membrane, activating adenylate cyclase, which catalyzes the production of the intracellular messenger cyclic AMP. Cyclic AMP in turn activates a specific protein kinase, which phosphorylates a yet unknown substrate for the propagation of the stimulatory signal. The action of acetylcholine on the oxyntic cell receptors does not stimulate the production of cyclic AMP; instead, it acts on Ca++ channels, increasing the Ca++ entrance into the cell, which initiates the intracellular events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of gastric acid secretion at the cellular level. 288 22

To determine possible sites and mechanisms of action of somatostatin (SS) in gastric secretory mucosa, secretion of pepsin, H+, Cl-, Na+ and K+ was stimulated in conscious fistula dogs by i.v. infusion of bethanechol, pentagastrin and histamine in the absence and presence of SS-14. At low dose (0.5 micrograms or 300 pmol/kg/h), SS-14 potently inhibited H+ and pepsin stimulated by bethanechol (80 micrograms/kg/h) to less than 5% of control; it required 2 micrograms or 1200 pmol/kg/h of SS-14 to achieve similar inhibition of pentagastrin (1.5 micrograms/kg/h)-stimulated secretion. In both cases, gastric [K+] was depressed by SS-14 infusion and recovered before H+ and pepsin. Similar sensitivity to SS suggests a Ca++-dependent mechanism or pathway of stimulation by gastrin similar to that by cholinergic agonists. By contrast, histamine, which acts via cyclic AMP pathways, was not inhibited by a large dose of SS-14 (20 micrograms/kg/h). SS inhibition is thus agonist (or pathway)- rather than organ- or cell-specific.
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PMID:Somatostatin effects on gastric electrolytes and pepsin in dogs with various secretory stimuli. 289 Jul 56

Parietal cell secretory function may be inhibited by three mechanisms. (1) Receptors for gastrin, histamine and acetylcholine are present on the canine parietal cell, and parietal cell function may be directly inhibited by specific antagonists for each of these receptors. (2) Receptor activation of parietal cell function is mediated by cyclic AMP-dependent (histamine) and calcium-dependent (cholinergic agents and gastrin) mechanisms. The antisecretory action of prostaglandins reflect interference with histamine activation of adenylate cyclase. The current generations of calcium channel blockers have only weak antisecretory actions in vivo and are unlikely to be useful in clinical practice. (3) A third mechanism of inhibition is blockade of H+/K(+)-ATPase by substituted benzimidazoles, such as omeprazole. Each of these three mechanism provides modalities of potential clinical usefulness for treating acid-peptic disease. Gastrin and acetylcholine receptors are present on other fundic cells, in addition to the parietal cell. These other cells include the somatostatin cell in the dog fundic mucosa and the histamine-containing enterochromaffin-like (ECL) cell present in the fundic mucosa of several species. The relative impact of these receptors on different cell types on the regulation of acid secretion remains uncertain, and is probably variable among different species. One gastrin receptor of considerable importance is the gastrin receptor that exerts a trophic effect on the ECL cell in the fundic mucosa. Sustained hypergastrinaemia in response to profound hypochlorhydria is associated with hyperplasia of this cell type; the elucidation of the conditions that promote this hyperplasia and the clinical consequences of this association are pressing challenges.
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PMID:Review: antisecretory drugs: cellular mechanisms of action. 297 19


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