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)

Using a newly developed system for culturing canine fundic mucosal cells, we examined regulation of the secretion of somatostatinlike immunoreactivity (SLI) by cholinergic and adrenergic transmitters. Enzyme-dispersed canine fundic mucosa cells were enriched in SLI content by counterflow elutriation and cultured on collagen for 42 h. Epinephrine alone, and in combination with gastrin, stimulated SLI secretion in a dose-dependent fashion. Propranolol did not alter the response to dibutyryl cAMP or gastrin but produced a parallel, rightward shift of the epinephrine dose-response curve with the dissociation constant (Ki) determined to be 14 nM by nonlinear curve fitting. Phentolamine, an alpha-adrenergic antagonist, enhanced SLI secretion in response to epinephrine, an effect reversed by the alpha 1-agonist methoxamine but not by the alpha 2-agonist clonidine. However, neither methoxamine nor clonidine alone inhibited the response to the beta-selective adrenergic agonist isoproterenol; thus, the existence of an adrenergic alpha 1-inhibitory receptor remained uncertain. Carbachol noncompetitively inhibited SLI secretion stimulated by gastrin, epinephrine, and dibutyryl cAMP. Atropine produced a parallel rightward shift of the carbachol dose-response curve (Ki = 0.4 nM). Pirenzepine also inhibited the effects of carbachol (Ki = 35 nM). Our studies suggest that SLI-containing cells in the canine fundic mucosa possess stimulatory beta-adrenergic receptors and inhibitory muscarinic receptors.
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PMID:Autonomic regulation of somatostatin release: studies with primary cultures of canine fundic mucosal cells. 614 98

Both pirenzepine and cimetidine have been shown to be beneficial in the healing of duodenal ulcers. The aim of the present study was to determine the effects of 50 mg of pirenzepine BID and 600 mg of cimetidine BID, either alone or in combination, on 24-hour intragastric acidity, nocturnal gastric secretory volume and acid output, and serum gastrin profile in patients with duodenal ulcers. Eight asymptomatic patients with healed duodenal ulcers received placebo, pirenzepine, cimetidine, or cimetidine plus pirenzepine for one week each in a sequential order. All measurements were performed over a 24-hour period on the last day of each treatment week. Compared with pirenzepine, cimetidine was associated with lower hydrogen ion (H+) activities after breakfast, during the night, and over the 24-hour period. Pirenzepine alone failed to suppress H+, but the combination of cimetidine plus pirenzepine resulted in more prolonged acid suppression, with lower H+ after lunch, than did cimetidine alone. The effect of cimetidine on the suppression of nocturnal acid secretory volume and acid output was further enhanced by the addition of pirenzepine. The fasting serum gastrin concentrations were similar in all treatments, excluding one patient with antral G-cell hyperplasia; the postprandial gastrin responses were similarly higher with cimetidine and cimetidine plus pirenzepine than with pirenzepine. The findings suggest an added benefit of combination therapy with cimetidine and pirenzepine that may be useful in patients who fail to respond to single-agent therapy.
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PMID:Comparative effects of pirenzepine and cimetidine, alone and in combination, on 24-hour gastric acidity in duodenal ulcer disease. 639 32

Gastric secretory functions and plasma gastrin levels in rats after the prolonged treatment of pirenzepine 2HCl were evaluated. Pirenzepine 2HCl at 100 mg/kg was given p.o. twice daily for 4 weeks. Control animals were given saline alone. The test agent potently inhibited gastric secretion in pylorus-ligated rats and fistula rats stimulated with pentagastrin and histamine before and after cessation of 4 weeks' treatment. At 1 day after the treatment, the acid output slightly decreased in pylorus-ligated rats and significantly decreased in fistula rats stimulated with secretagogues. At 3 days, the acid output was slightly increased in pylorus-ligated rats and significantly increased in fistula rats stimulated with pentagastrin but was unchanged in the case of histamine stimulation. At 10 days, the gastric secretion in pylorus-ligated rats tended to increase but the acid output in fistula rats was not affected. Pirenzepine 2HCl increased the plasma gastrin levels in normal rats and at 1 day after the treatment, but had no effects at 3 and 10 days. Propantheline Br showed much the same results as seen with pirenzepine 2HCl. Cessation of prolonged treatment with pirenzepine 2HCl appears to increase only slightly and transiently the sensitivity of gastric secretory cells.
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PMID:Effects of prolonged treatment of pirenzepine 2HCl on gastric secretion and plasma gastrin levels in rats. 689 23

Combinations of H2-receptor antagonists and classical anticholinergics inhibit stimulated gastric acid secretion more than either drug alone. In double blind, placebo controlled, randomised studies we have compared the effects of single and combined intravenous bolus injections of cimetidine and pirenzepine on peptone-stimulated acid secretion and serum gastrin in man. Combined injection of 3.0 mg/kg cimetidine and 0.3 mg/kg pirenzepine suppressed stimulated acid secretion significantly more than either drug alone, and by 90% in healthy volunteers (n = 8) and patients with duodenal ulcer (n = 5). Side-effects (prolactin stimulation, blurred vision) were diminished by reducing the combined dosages to 1.5 mg/kg cimetidine, to 0.075 and 0.15 mg/kg pirenzepine in another series (n = 10). Postprandial gastrin was not affected by any combination. Combination of cimetidine and pirenzepine suppress food-stimulated gastric secretion more effectively than combination of H2-blockers with classical anticholinergics. Pirenzepine--unlike classical anticholinergics--may distinguish between different subclasses of muscarinic receptors and have a more selective antimuscarinic action. Its interaction with H2-receptor antagonists on parietal cell function seems to be synergistic. Such a combination could be of advantage in patients with gastrinoma, in patients with ulcers and hypersecretion resistant to single drug treatment, and in critically ill patients as prophylaxis of stress ulcer bleeding.
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PMID:Interactions of cimetidine and pirenzepine on peptone-stimulated gastric acid secretion in man. 694 73

Pirenzepine exerted a powerful inhibitory effect on gastric acid secretion from both the gastric fistula and the Heidenhain pouch of the dog, following intravenous infusion of bombesin. Similar results were obtained from the Heidenhain pouch when hypersecretion was stimulated by the meal test. The rise in plasma levels of radioimmunological gastrin, obtained by either bombesin or food administration, was not significantly affected by pirenzepine. The overall results indicate that the inhibitory effect of pirenzepine on gastric acid secretion in the dog was independent from the release of endogenous gastrin.
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PMID:The effect of pirenzepine on gastric acid secretion and gastrin release induced by bombesin and meal in the dog. 695 77

Pirenzepine is a new antimuscarinic drug with a peculiar affinity for gastric parietal cells' acetylcholine receptors. Previously it has been shown that the drug effectively inhibits both basal and gastric acid secretion stimulated by several secretagogues. The aim of the present work has been to evaluate, in double-blind, placebo controlled, randomized studies on 6 male patients, the effect of pirenzepine (50 mgs orally) on gastric secretion stimulated by peptone meal, gastric emptying and gastrin release. The results show a significant decrease of gastric secretion (48 per cent in the 1st and 30 per cent in the 2nd hour) without any effect on gastric emptying and gastrin release.
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PMID:The effect of pirenzepine on meal-stimulated gastric acid secretion, gastrin release and gastric emptying. 695 83

This report tests in men the effect of Pirenzepine on L-Amino acids stimulated gastric secretion and serum gastrin levels in order to evaluate the true antimuscarinic selective properties of this drug. Since L-Amino acids given intravenously stimulate gastric acid secretion by a mechanism of action selective on the cholinergic receptors of the gastric parietal cells, not mediated through the vagus nerve, gastrin or other gut hormones. Pirenzepine should be an L-Amino acids antagonist as far as the gastric acid secretion is concerned. By confirming this presumed antagonism between Pirenzepine and L-Amino acids given intravenously, this report points out in men the selective antimuscarinic effect of this anti ulcer drug on the high affinity muscarinic receptors of the gastric parietal cells. Finally a decrease in gastrin serum levels was observed after the i.v. administration of Pirenzepine and this could be explained by a possible effect of blockade of this drug on the cholinergic receptors of the antral G cells, but these data need further experimental confirm. Attention is then paid to the different mechanism of action between Pirenzepine, H2 receptors antagonist drugs and other anti ulcer drugs on healing gastric or duodenal peptic ulcers.
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PMID:Effect of pirenzepine on L--amino acids stimulated gastric acid secretion and serum gastrin levels in peptic ulcer disease in men. 695 88

The functional role of the cholinergic nervous system in regulating gastrin release was investigated using enriched canine antral G cells. Gastrin content was 30.1 +/- 2.9 pmol per well and basal gastrin release was 900 +/- 27 fmol per well (n = 45). Carbachol (10(-8) to 10(-5) M) dose-dependently stimulated gastrin release with a maximal stimulatory response achieved at a concentration of 10(-5) M (330% over basal). To characterize the muscarinic receptor which mediates gastrin release from antral G cells, we examined the effect of three muscarinic receptor antagonists on carbachol-stimulated gastrin release; atropine (nonselective muscarinic receptor antagonist), pirenzepine (M1 muscarinic receptor antagonist) and 4-DAMP (M3 muscarinic receptor antagonist). Atropine (10(-9) to 10(-6) M), pirenzepine (10(-8) to 10(-5) M) and 4-DAMP (10(-9) to 10(-6) M) had no effect on the basal gastrin release. However, carbachol (10(-5) M)-stimulated gastrin release was effectively inhibited by atropine and 4-DAMP with Ki values of 0.48 and 0.66 nM, respectively. Pirenzepine at a high concentration (10(-5) M) also inhibited carbachol-stimulated gastrin release with a Ki value of 46.3 nM. These results suggest that the cholinergic nervous system directly stimulates gastrin release via M3 muscarinic receptors located on antral G cells.
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PMID:Muscarinic M3 receptor-mediated release of gastrin from canine antral G cells in primary culture. 789 29

We evaluated gastric juice secretion during extracorporeal circulation (ECC) in cardiac surgery. The effect of pirenzepine, a muscarine receptor blocker, was also tested to clarify the mechanism involved. Gastric juice secretion increased significantly from pre ECC value of 3.8 +/- 1.3 ml.h-1 to 12.4 +/- 4.0 ml.h-1 during ECC. It decreased to 5.0 +/- 1.4 ml.h-1 (mean +/- SE) after ECC. Pirenzepine premedication reduced serum gastrin level. However, it did not suppress the increase of gastric juice secretion. There is no significant correlation between serum gastrin level and gastric juice secretion. ECC is a major stress and increases gastric juice secretion. This phenomenon is probably activated via sympathetic and hypophysis-adrenal gland system.
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PMID:[Gastric juice secretion increases during extracorporeal circulation employed in cardiac surgery]. 793 68

Pirenzepine has inhibitory effects on gastrin secretion both in vivo and in vitro. The aim of this study was to determine the mechanism responsible for the suppression of omeprazole-induced hypergastrinemia that occurs with pirenzepine treatment. The effects were measured in rats treated with oral omeprazole plus intraperitoneal pirenzepine or saline once daily for seven days in the antrum. The serum gastrin level increased significantly by more than sixfold with omeprazole treatment; additional treatment with pirenzepine suppressed this increase by 48%. Pirenzepine treatment did not change the level of gastrin mRNA but significantly increased the level of somatostatin mRNA. Combination treatment with omeprazole plus pirenzepine significantly decreased the gastrin mRNA level to half and significantly increased the somatostatin mRNA level up to 1.4-fold of the levels achieved with omeprazole treatment alone. These results suggest that the stimulatory effect of omeprazole on gastrin synthesis is partially blocked by pirenzepine via mediation of somatostatin synthesis in the antrum.
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PMID:Effects of pirenzepine on omeprazole-induced gastrin gene expression in rat antral tissues. 865 46


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