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)

We have studied the physiologic factors regulating oxyntic cell activity using cytochemical quantification of carbonic anhydrase (CA) activity. Gastrin (10 (-16) to 10(-12)M), histamine (10(-17) to 10(-13) M), and carbamylcholine (10(-13) to 10(-8) M) caused a dose-dependent increase in CA in the oxyntic cells in guinea pig gastric fundus, maximal at 90 sec. The stimulation of CA by all three secretagogues was inhibited by the CA inhibitor, acetazolamide. The agonist activities were selectively blocked by respective antagonists. The benzimidazole derivative compound Hassle 149/94 (10(-3)M) abolished the actions of all agonists. Thus, histamine, gastrin and carbamylcholine have independent actions on oxyntic cell CA. The inhibition of the activity of all three secretagogues by H149/94 suggests a close link between CA activity and the functioning of the proton pump H+ + K+-ATPase.
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PMID:Cytochemical quantification of physiologic regulation of oxyntic cell carbonic anhydrase. 643 Jan 97

Virtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUs) are the consequence of Helicobacter pylori-associated inflammation. In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb. Gastrin homeostasis is disturbed by H. pylori gastritis and there is robust acid secretion. Successful eradication of the infection cures the ulcer diathesis. Amalgamated figures for ulcer relapse per year in H. pylori-positive DUs are > 60% compared with 2.6% for H. pylori-negative DU patients. The corresponding figures for GU are > 50% for H. pylori-positive and 2.0% for H. pylori-negative individuals. This striking difference in relapse rate persists, as the re-infection rate in the developed world is < 1% per year. Recurrent bleeding in bleeding-prone DUs is essentially abolished after cure of the infection. Proton pump inhibitors (PPIs) are increasingly used in eradication regimens. PPIs have intrinsic antimicrobial activity. MICs for lansoprazole (LAN) are lower than for omeprazole (OME). Two weeks of triple therapy (bismuth, tetracycline, imidazole) has, on average, a superior eradication efficacy (> or = 90%) compared with dual therapy (PPI, amoxycillin or clarithromycin) (> or = 80%). When a combination of PPI and two antibiotics has been used, results comparable to triple therapy have been reported. However, the side-effects profile and patient acceptability of PPI plus one or two antibiotic regimens are better than for traditional triple therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No Helicobacter pylori, no Helicobacter pylori-associated peptic ulcer disease. 749 41

The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.
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PMID:A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas. 752 49

To evaluate endogenous and exogenous factors affecting the quality of ulcer healing produced by proton pump inhibitors, gastric acid pH, serum gastrin, and serum pepsinogen (PG) I and II were measured in peptic ulcer patients before and after treatment with lansoprazole 30 mg once daily. Lansoprazole achieved more rapid scarring in duodenal ulcer (n = 34), with a healing rate of 97.1% after 6 weeks, than in gastric ulcer (n = 56), with a healing rate of 92.8% after 8 weeks. Scarring was the most rapid in gastroduodenal ulcer (n = 8), with a healing rate of 100% after 8 weeks, but the rate of complete scarring was the lowest (37.5%). Lower gastric acidity and lower PG I:II ratio were associated with poor quality ulcer scarring in patients with gastric ulcers, but the opposite was true for those with duodenal and gastroduodenal ulcers. For gastric ulcers, not only ulcer size but also mucosal atrophy was an important factor in ulcer healing. Smoking and alcohol consumption had little effect on the quality of ulcer healing during treatment. These results suggest that there are a number of differences between gastric ulcers and duodenal ulcers in terms of the quality of ulcer healing after lansoprazole treatment.
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PMID:Factors affecting quality of ulcer healing after lansoprazole treatment. 759 44

Omeprazole is a potent antisecretory drug that acts by inhibiting the gastric proton pump. In the present study, we have observed the effects of this drug on gastrointestinal mucosal perfusion, oxygenation, and hexosamine generation in humans. Sixteen healthy volunteers were included. Gastrointestinal mucosal perfusion and oxygenation (duodenum, antrum, and corpus) were assessed by laser-Doppler flowmetry and reflectance spectrophotometry. Biopsy specimens were also taken from each location to determine hexosamine content as a quantitative indicator of mucus generation. In addition, serum gastrin level was measured. After baseline data were obtained, subjects were randomly assigned to receive 20 mg of oral omeprazole once daily for 7 days (n = 8) or placebo (n = 8). All measurements were performed again after double-blinded drug administration. No effect was found after placebo administration. In contrast, omeprazole administration significantly increased serum gastrin level (p < .05), suggesting an inhibition of acid secretion. However, this drug did not alter either laser-Doppler signal or oxygen saturation at each location. In addition, no change in mucosal hexosamine content was observed at each location. We conclude that oral omeprazole, despite its well-established antisecretory effect, has no adverse effect on the mucosal defense in humans.
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PMID:Omeprazole administration does not impair gastrointestinal mucosal perfusion, oxygenation, and hexosamine generation. 761 30

The effect of omeprazole, a proton pump inhibitor, on the forward passage of the crop contents of chicks receiving 20% medium chain or long chain triacylglycerol was studied. Medium chain triacylglycerol significantly delayed the crop emptying of chicks compared with long chain triacylglycerol. Omeprazole also significantly inhibited passage from the crop of the long chain triacylglycerol meal. Application of omeprazole induces achlorhydria and consequently hypergastrinemia but chicken gastrin lower than 100 nmol/kg did not delay crop emptying. The addition of hydrochloric acid (HCl) to the diet reversed the action of omeprazole on the crop emptying of chicks. We conclude, then, that omeprazole delayed the crop emptying in chicks as a consequence of inhibition of acid secretion, although the mediator is not gastrin.
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PMID:Inhibition of food passage by omeprazole in the chicken. 773 10

Twelve healthy volunteers (6 females, 6 males) between 26 and 36 years of age were enroled in this double-blind, randomized, placebo-controlled, three-way cross-over study. The objective was to determine the influence of lansoprazole (Agopton, Takeda Pharma GmbH, Aachen), a novel proton pump inhibitor, in doses of 30 and 60 mg, on the intragastric pH, on meal-stimulated gastric acid secretion and on the concentration of gastrointestinal hormones and enzymes in serum and gastric juice. Active drug or placebo had to be taken as single daily morning doses on an empty stomach for 7 days. Each wash-out period between drug application periods was 2 weeks long. Lansoprazole induced a dose-related increase in intragastric pH as well as a relevant reduction of basal acid output, meal-stimulated acid output and meal-stimulated secretion volume. 60 mg lansoprazole was significantly superior to 30 mg in increasing intragastric pH. The basal secretion volume in volunteers on 30 and 60 mg lansoprazole were lower than in volunteers on placebo. Serum gastrin and serum pepsinogen concentrations increased in a dose-dependent manner. Pepsin output and pepsin activity in gastric juice were slightly decreased in volunteers on 30 mg lansoprazole and markedly suppressed in volunteers on 60 mg lansoprazole 2 h after meal stimulation. Intrinsic factor concentration increased in volunteers on lansoprazole with a clear dose relationship. The evaluation of laboratory data and reported nonserious adverse events proved the relative safety of this new antiulcer agent.
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PMID:Influence of lansoprazole on intragastric 24-hour pH, meal-stimulated gastric acid secretion, and concentrations of gastrointestinal hormones and enzymes in serum and gastric juice in healthy volunteers. 775 Jun 67

RP 73870, the racemic potassium salt of (([N-(methoxy-3-phenyl)-N-(N-methyl-N-phenyl-carbamoylmethyl)- carbamoylmethyl]-3-ureido)-3-phenyl)-2-ethylsulfonate-(RS) is a potent, reversible antagonist of both gastrin and cholecystokinin-B receptors in guinea pig and rat tissues. This compound is a potent inhibitor of pentagastrin-stimulated gastric acid secretion in the perfused rat stomach. RP 73870 also inhibits basal gastric acid secretion in the rat, although at doses higher than that required for inhibition of pentagastrin-stimulated gastric acid secretion. RP 73870 is a potent inhibitor of aspirin-induced gastric damage in the rat. In the prevention of aspirin-induced gastric damage, RP 73870, given p.o., was 10-fold less potent than when given i.v. RP 73870 was as potent as a H2 receptor antagonist or proton pump inhibitor in the prevention of cysteamine-induced duodenal ulcers in the rat. Relative to other gastrin/cholecystokinin-B antagonists, RP 73870 demonstrates greater affinity to gastrin binding sites, and possesses a unique spectrum of in vivo biological activities appropriate for an anti-ulcer indication.
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PMID:RP 73870, a gastrin/cholecystokinin-B receptor antagonist with potent anti-ulcer activity in the rat. 779 Oct 71

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.
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PMID:Optimizing acid suppression for treatment of acid-related diseases. 785 82

Our previous study revealed that the gastric vagus nerve plays an etiologic role in immobilization (IMB) stress-induced hypocalcemia. The purpose of the present study is to identify exactly what parts of the stomach are involved in the development of IBM-induced hypocalcemia and to determine whether or not gastric acid secretion is involved. A total gastrectomy, but not a resection of the upper intestine, eliminated the hypocalcemic effect of IMB. In addition, either an antrectomy (removal of the source of gastrin) or a fundectomy (depriving the origin of gastric histamine and gastric acid) was sufficient for eliminating IMB-induced hypocalcemia, while a partial (50%) fundectomy failed to suppress it. An intraperitoneal injection of galanin (an inhibitor of gastrin release) or ranitidine (a blocker of histamine H2-receptor) also suppressed the calcium-lowering effect of IBM, whereas omeprazole (an inhibitor of the proton pump) had no effect. These findings suggest that the antrum and the fundus of the stomach play essential roles in IMB-induced hypocalcemia through the vagus-induced release of gastrin and histamine but not through the secretion of gastric acid per se.
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PMID:The stomach is the etiologic organ for immobilization-induced hypocalcemia in rats. 790 26


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