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)

Ebrotidine is a novel H2-receptor antagonist that exhibits both gastroprotective and ulcer-healing properties. Gastroprotection afforded by ebrotidine against ethanol damage was observed only after intragastric, but not parenteral administration, and it was accompanied by an increase in the mucosal blood flow. Ranitidine given at the same dose (100 mg/kg i.g. or s.c.) did not show any protective activity. When administered twice daily at various doses (1-100 mg/kg) for 10 days, ebrotidine reduced dose dependently the area of chronic gastric ulcers, and it was accompanied by significantly higher contents of epidermal growth factor (EGF) in the ulcer bed than in the intact mucosa. Administration of ranitidine resulted in a similar rate of ulcer healing and in a similar accumulation of EGF in the ulcer area to that observed after ebrotidine, but the increments in plasma gastrin levels in rats treated with ranitidine were observed at lower doses than in tests with ebrotidine. Concurrent administration of indomethacin delayed ulcer healing and reduced the accumulation of EGF in the ulcer area, but did not affect the ulcer healing by ebrotidine or ranitidine. We conclude that ebrotidine but not ranitidine shows gastroprotective activity, but it enhances the healing of chronic ulcerations in a similar manner to ranitidine.
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PMID:Gastroprotective and ulcer-healing activities of a new H2-receptor antagonist: ebrotidine. 135 65

In conscious, gastric fistula rabbits, gastric acid and pepsin secretion averaged 4.5 +/- 0.1 mmol/h (1.3 mmol.kg-1.h-1) and 4.9 +/- 0.3 IU/h (1.6 IU.kg-1.h-1), respectively; these values represent approximately 40-50% of maximal output. Basal serum gastrin concentrations averaged 24 +/- 4 pg/ml and did not correlate with basal acid secretion. Atropine and vagotomy incompletely inhibited basal acid secretion (by 84 and 50%, respectively) and completely inhibited 2-deoxy-D-glucose-stimulated gastric acid secretion. Atropine and vagotomy similarly inhibited basal pepsin secretion by 50 and 40%, respectively. Ranitidine decreased acid and pepsin secretion, but as with atropine, inhibition was not complete (73 and 37%, respectively). Although omeprazole did not affect pepsin secretion, omeprazole completely inhibited basal acid secretion and elevated postprandial intragastric pH above 5.0. Conscious, gastric fistula rabbits have the highest basal acid and pepsin output among species commonly studied. Both vagal-cholinergic pathways and histamine drive basal acid and pepsin secretion in the rabbit.
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PMID:Gastric acid and pepsin hypersecretion in conscious rabbits. 167 87

1. The urethane-anaesthetized, vagotomised rat preparation was used to investigate the effects of the histamine H2-antagonist ranitidine, the proton pump inhibitor omeprazole and the CCKB/gastrin antagonists CI-988, PD 136450 and L-365,260 on pentagastrin-, histamine- and bethanechol-induced gastric acid secretion. 2. The novel CCKB/gastrin antagonists CI-988 and PD 136450, and L-365,260 dose-dependently inhibited pentagastrin-induced secretion. The ED50 value for PD 136450 was 0.05 mumol kg-1, the same following intravenous or subcutaneous administration. 3. CI-988 and PD 136450 administered subcutaneously at dose levels highly effective for antagonism of pentagastrin responses had no effect on basal acid secretion. 4. Ranitidine inhibited pentagastrin-, bethanechol-, and histamine-induced acid secretion, whereas the CCKB/gastrin antagonists inhibited only the secretory response to pentagastrin. 5. The selective CCKA antagonist, devazepide, was inactive at up to 300 mumol kg-1 i.p. against the three stimulants of acid secretion. 6. CI-988 and PD 136450 will be useful research tools with which to investigate the role of CCKB/gastrin receptors in gastric acid secretion and the trophic activities of gastrin and cholecystokinin (CCK) on the gastrointestinal tract.
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PMID:The effect of CCKB/gastrin antagonists on stimulated gastric acid secretion in the anaesthetized rat. 168 71

Nizatidine (N-[2-[[[2-[(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2) is a new histamine H2-receptor antagonist which shows suppression of gastric acid secretion and antiulcer activity. In the present experiment, the effects of single s.c. administration of nizatidine, cimetidine and ranitidine on serum gastrin levels were studied in fasted rats. Nizatidine at 100 mg/kg increased serum gastrin level 3 h after administration, which however, returned to basal level 6 h after administration. Cimetidine and ranitidine at respective doses of 250 and 100 mg/kg markedly increased serum gastrin levels 3 and 6 h after administration. In a previous study, the suppressive effect of nizatidine on basal gastric acid secretion was 82.8% at a dose of 100 mg/kg s.c. in rat pylrus-ligated model. On the basis of these findings, changes in basal gastric acid secretion and serum gastrin level after withdrawal of nizatidine, cimetidine and ranitidine administered for 14 consecutive days were studied. One day after withdrawal, nizatidine at 100 mg/kg showed a tendency to increase the basal gastric acid secretion. However, 3 and 7 days after administration, almost no changes were obtained. Cimetidine at 250 mg/kg showed a tendency to increase the basal gastric acid secretion 7 days after withdrawal of the drug. Ranitidine at 100 mg/kg induced no changes in basal gastric acid secretion after withdrawal. No obvious influences of all drugs on serum gastrin level after withdrawals were obtained. These results indicate that consecutive administration of nizatidine may cause only a transient increase of gastric acid secretion but no hypergastrinaemia after its withdrawal.
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PMID:Effects of successive doses of nizatidine, cimetidine and ranitidine on serum gastrin level and gastric acid secretion. 179 24

Although in most patients with duodenal ulcer disease the ulcer heals after 8 weeks of treatment with standard doses of H2 blockers or other agents, in about 10% the ulcer does not heal. These patients are considered 'refractory' to treatment. Reasons often cited for non-healing include poor patient compliance, cigarette smoking, and non-steroidal anti-inflammatory drug (NSAID) use. Gastric acid hypersecretion also appears to be an important factor in non-healing with standard doses of antisecretory agents. We have defined idiopathic gastric acid hypersecretion as a basal acid output of greater than 10 mmol/h in the absence of an elevated fasting serum gastrin level (or a negative secretin test if gastrin level greater than 100 pg/ml) to exclude persons with Zollinger-Ellison syndrome. Among the acid/peptic-related disorders in which idiopathic gastric acid hypersecretion should be considered are refractory duodenal ulcer, refractory gastro-oesophageal reflux disease (especially patients with oesophagitis), postbleeding duodenal ulcer, and certain rare disorders such as hereditary angioedema. Some children with atypical abdominal pain may also be hypersecretors of gastric acid. Once identified, patients with refractory duodenal ulcer or gastro-oesophageal reflux disease are treated with incremental doses of ranitidine titrated against the level of gastric acid secretion that remains during therapy. Ranitidine was selected to avoid the dose-related antiandrogenic effects and potential hepatic cytochrome P450 system-related drug interactions that may occur with cimetidine. In most cases of refractory duodenal ulcer, doubling the standard dose of ranitidine (to 300 mg b.d.) is sufficient to achieve symptomatic relief and mucosal healing. Higher doses appear to be necessary for refractory oesophagitis. To date, no side effects have been associated with high doses of ranitidine (up to 1800 mg/day) for periods of longer than 6 months. Idiopathic gastric acid hypersecretion is an important factor in explaining why not all patients respond to a 'standard' ulcer-healing dose of H2 blocker, and it provides a rationale for use of higher-dose therapy as a safe and effective alternative to omeprazole or to combination drug therapy in refractory acid/peptic disease.
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PMID:Idiopathic gastric acid hypersecretion: treatment implications for refractory acid/peptic disorders. 188 34

Pancreatico-biliary diversion (PBD) stimulates pancreatic growth in the rat. The present experiment was designed to investigate the mechanism of this phenomenon. The potential roles of endogenous CCK, gastrin, and secretin were studied. Hormone measurements by specific RIA's show that PBD was associated with higher CCK plasma concentrations and, conversely, with lower gastrin circulating levels. Secretin and pancreatic polypeptide were unaffected by PBD. Seven days' subcutaneous administration of proglumide (1000 mg/kg/day), benzotript (100 mg/kg/day), two CCK and gastrin receptor antagonists, and Ranitidine (100 mg/kg/day) resulted in a significant inhibition of PBD-induced pancreatic growth, assessed by measurements of pancreatic weight, DNA, RNA and protein content. These results suggest, therefore, that CCK plays a central role in the development of the pancreatic adaptive response to PBD.
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PMID:Mechanism of pancreatic growth induced by pancreatico-biliary diversion in the rat. Inhibition by proglumide, benzotript, and ranitidine. 240 83

1. In the isolated vascularly-perfused stomach of the rat, gastrin 1-17 (520 pmol 1(-1)) increased acid output from basal values of 13.7 +/- 2.7 to 92.5 +/- 11.4 mumol h-1 and venous histamine output from 10.1 +/- 2.3 to 54.7 +/- 7.9 nmol h-1 (mean +/- s.e.mean). 2. The H1 receptor agonist 2-methylhistamine (10 mumol 1(-1)) increased acid output to 21.6 +/- 2.9 mumol h-1 (P less than 0.05) and reduced basal histamine output to 4.0 +/- 0.8 nmol h-1 (P less than 0.05). Gastrin-stimulated acid secretion and vascular histamine output was not significantly affected by 2-methylhistamine (10 mumol 1(-1)). 3. The H2 receptor agonist, impromidine, dose-dependently increased basal acid secretion, reaching a maximal value of 145.5 +/- 11.7 mumol h-1 with impromidine (10 mumol 1(-1)), and maximal gastrin-stimulated acid secretion to 167.4 +/- 15.1 mumol h-1 with impromidine (10 mumol 1(-1)). Impromidine dose-dependently inhibited basal and gastrin-stimulated vascular histamine output. 4. The H3 receptor agonist R-a-methylhistamine, (1 and 10 mumol 1(-1)) minimally increased basal acid secretion. R-a-methylhistamine (10 mumol 1(-1)) did not significantly affect maximal gastrin-stimulated acid secretion. Basal and gastrin-stimulated vascular histamine outputs decreased to 4.0 +/- 0.8 (P less than 0.05) and 24.7 +/- 4.7 nmol h-1 (P = 0.05) with R-a-methylhistamine (10 mumol 1(-1)). 5. The H2 receptor antagonist ranitidine (2 mumol 1(-1)) did not inhibit basal acid secretion, but acid outputs with gastrin and all histamine agonists were reduced. Ranitidine did not affect histamine release in the basal state, with gastrin or with any histamine agonist tested. 6 We conclude that gastric histamine release in the rat is regulated via a histamine H2 receptor sensitive to the histamine agonists tested, but not to ranitidine. It is unlikely that the inhibition of histamine release is secondary to increased gastric acidity.
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PMID:Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors. 247 Apr 53

In the rat, treatment with gastric inhibitory drugs may result in hypergastrinemia, an effect thought to be in response to increased gastric pH caused by inhibition of acid secretion. This study compared 24-hr profiles of plasma gastrin levels associated with three different compounds at equivalent, highly effective antisecretory doses. Ranitidine, famotidine and omeprazole at 60, 20 and 40 mg/kg p.o., respectively, inhibited basal acid secretion of chronic gastric fistula rats by greater than 95% and raised intraluminal pH to above 7.0 for 5 hr. The peak plasma gastrin levels associated with each agent were observed 5 hr after dosing. Ranitidine, famotidine and omeprazole induced statistically significant and distinct peak hypergastrinemic responses of 312 +/- 20, 483 +/- 28 and 616 +/- 27 pg/ml, respectively. After 8 hr ranitidine and famotidine associated gastrin values returned to control levels, whereas those of omeprazole remained substantially above control values until the 12th hr. Differences in peak gastrin levels between compounds disappeared at increased dose levels of 500 mg/kg for ranitidine, 200 or 2000 mg/kg for famotidine and 140 mg/kg for omeprazole. Unlike high dose famotidine, omeprazole (140 mg/kg) maintained peak plasma gastrin levels at 8, 12, and 16 hr after dosing. These studies demonstrate clearly hypergastrinemic responses to single dose administration of ranitidine, famotidine and omeprazole. The differences observed in peak plasma gastrin levels at equivalent antisecretory doses of these agents suggests the presence of luminal acid independent components that effect gastrin release. Moreover, these studies indicate that, in the rat, the most unique aspect of omeprazole-associated hypergastrinemia is the magnitude of its prolonged response.
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PMID:Acute effects of ranitidine, famotidine and omeprazole on plasma gastrin in the rat. 256 84

Female rats were treated for 28 days with high doses of the gastric acid secretion inhibitors omeprazole and ranitidine. Omeprazole, which is long-acting, was given orally once daily. Ranitidine, which is short-acting, was given by continuous infusion (via osmotic minipumps, implanted subcutaneously). The aim was to produce a similar degree of acid inhibition with the two drugs. The inhibition of acid secretion over the day and night was more pronounced in the omeprazole-treated rats (maximal inhibition 100%, minimum 85%) than in those receiving ranitidine (mean 70%). In both groups, there was a great increase in plasma gastrin, somewhat greater after omeprazole than after ranitidine. The gastrin concentration in the antrum was almost doubled by both treatments and there was a moderate increase in the number of antral gastrin cells in the omeprazole-treated rats. The number of enterochromaffin-like (ECL) cells (per visual field) increased in the oxyntic mucosa to the same extent (greater than 100%) in the ranitidine- and omeprazole-treated rats. Apart from the gastrin cells in the antrum and the ECL cells in the corpus no other gastric endocrine cell type seemed to respond to treatments with antisecretagogues. We conclude that, regardless of the type of antisecretagogue used, effective and long-term suppression of gastric acid secretion results in sustained hypergastrinemia and increased number of ECL cells. Conceivably therefore, the ECL cell hyperplasia reflects the trophic effect of gastrin.
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PMID:Omeprazole and ranitidine, antisecretagogues with different modes of action, are equally effective in causing hyperplasia of enterochromaffin-like cells in rat stomach. 275 57

The effect of enprostil, a synthetic dehydro-prostaglandin E2, on meal-stimulated gastric acid secretion and gastrin release was studied in six patients with inactive duodenal ulcer disease. Each subject underwent seven tests in random order on separate days: placebo intragastrically and intraduodenally; enprostil 35 and 70 micrograms both intragastrically and intraduodenally; and ranitidine 150 mg intragastrically. After measuring basal gastric acid secretion and gastrin release, a liquid meal (500 ml, pH 5.5, 40 g protein, 30 g fat, 30 g carbohydrate, 550 Kcal, 768 mOsm) was given. Gastric acid secretion and gastrin release were measured over the next four hours. A second identical meal was instilled and both parameters were measured for an additional four hours. Thirty-five and 70 micrograms of enprostil administered intragastrically reduced total eight-hour gastric acid secretion by 58 percent and 82 percent, respectively (p less than 0.05). The 35 and 70 microgram doses administered intraduodenally decreased gastric acid secretion by 67 percent and 91 percent, respectively (p less than 0.05 compared with placebo). Ranitidine suppressed gastric acid secretion by 95 percent, which was similar to the suppression achieved with the 70 microgram dose of enprostil. The total meal-stimulated integrated gastrin response was significantly suppressed by both intragastric doses of enprostil and by the 70 microgram dose given intraduodenally (p less than 0.05). Compared with placebo, the 35 microgram intragastric and intraduodenal doses decreased the integrated gastrin response by 73 percent and 72 percent, respectively. The 70 microgram intragastric and intraduodenal doses of enprostil reduced the integrated gastrin response by 90 percent and 125 percent, respectively. Ranitidine did not alter the integrated gastrin response. It is concluded that enprostil significantly inhibited both meal-stimulated gastric acid secretion and gastrin release. The response to enprostil occurred in a dose-dependent manner and was similar regardless of the route of administration.
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PMID:Enprostil, a synthetic prostaglandin E2 analogue, inhibits meal-stimulated gastric acid secretion and gastrin release in patients with duodenal ulcer. 309 54


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