Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of topical application of omeprazole on transmucosal potential difference (PD), luminal pH and histamine-stimulated acid secretion were examined in anesthetized rat stomachs, and they were compared with those of systemic administration. Omeprazole was suspended in 1% CMC with NaHCO3 (pH 9.0) or dissolved in 0.1 N HCl (pH 1.0). Both omeprazole (30 mg/kg, pH 9.0) and cimetidine (100 mg/kg), given i.d., increased the pH and inhibited acid secretion induced by histamine (8 mg/kg/hr, i.v.), while basal gastric PD was markedly elevated only by the former. Similar responses in PD, pH and acid output were obtained dose-dependently after brief exposure of the stomach (10 min) to omeprazole (0.3-30 mg/kg), even in acidic conditions, but the effects of acidified omeprazole disappeared depending upon the latency period in 0.1 N HCl; there was no effect when applied at more than 30 min after dissolution. Of interest, subsequent exposure of the stomach to a mercaptane compound (cysteine, 100 mg/kg) for 30 min significantly reversed the antisecretory effect of omeprazole (both i.d. and i.g.) but not of cimetidine. These results suggest that omeprazole has a local antisecretory action even in acidic stomachs, probably through an inhibition of the H+/K+ATPase activity, and the increase of PD caused by omeprazole may be a characteristic phenomenon seen after the blockade of H+/K+ ATPase, but is not associated with acid inhibition itself.
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PMID:Effects of topical application of acidified omeprazole on acid secretion and transmucosal potential difference in anesthetized rat stomachs. 318 68

Guinea-pig gastric mucosal cells isolated by collagenase and pronase digestion were used to study the release of prostanoids prostaglandin I2 (PGI2; measured as 6-keto PGF1 alpha), PGE2, PGF2 alpha and thromboxane A2 (TXA2; measured as TXB2). Lysophosphatide acyltransferase (LAT) and phospholipase A2 (PLA2) were measured in the microsomal fraction of isolated but not separated gastric cells and isolated and enriched parietal and mucous cells. In all cell preparations PLA2 activity was approximately 5 times higher than that of LAT. Acid-activated omeprazole inhibited LAT in a concentration-dependent manner with similar IC50 values in gastric, parietal and mucous cells. It had no effect on PLA2. Gastric cells constantly produced PGI2, PGE2, PGF2 alpha and TXA2. The main prostaglandins released were PGI2 and PGE2. PGF2 alpha and TXA2 were released in smaller quantities. Omeprazole dissolved in polyethylene glycol 400 (PEG) pH 2 inhibited spontaneous PGI2 release in a concentration-dependent manner with an IC50 of 14.3 +/- 4.8 microM. Only concentrations as high as 100 microM produced a significant reduction in PGE2 release by 60%. No significant changes could be detected in the spontaneous release of PGF2 alpha and TXA2. Omeprazole dissolved in PEG pH 7 had no effect on PGI2 release except at 100 microM which led to an insignificant decrease by 40%. These data suggest that omeprazole beyond its inhibitory effect on parietal cell K+/H+-ATPase also affects gastric mucosal prostanoid formation and release. The inhibitory effect on PGI2 does not support the view that omeprazole protects the gastric mucosa by increasing prostanoid formation.
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PMID:Effect of omeprazole on eicosanoid formation in and release from guinea-pig gastric mucosal cells. 329 28

A new model for measuring gastric secretory parameters in awake guinea pigs is described. A chronic cannula was surgically implanted in the stomach of each guinea pig. The rates of gastric secretion and changes in intragastric volume were measured using a dye dilution technique. In contrast to previous techniques in small laboratory animals, there was no collection of gastric juice via drainage, no oral intubation for aspiration was involved, no special or sophisticated equipment was used, no anesthesia was employed, and there was no stress associated with acute surgery. This method offers a valuable advantage by combining the chronic gastric cannula with a dye dilution technique in that the same animal can be used several times and finally, several gastric secretory parameters can be measured simultaneously. The animals were used from 3 weeks to 10 months after surgery and as many as 15 studies were performed on the same guinea pig. Samples were collected at 10-min intervals and analyzed for acid and dye concentration from which the onset and kinetics of gastric secretion were followed. Basal gastric secretion (11.8 +/- 1.6 mueq/kg/min; all mean +/- 1 SEM) was increased within 20 min after subcutaneous infusion of histamine (30 micrograms/kg/hr) and peaked by 40-60 min at a mean acid output rate of 41 +/- 3 mueq/kg/min. Histamine also increased the intragastric volume from 6.3 to 13.4 ml as it increased fluid output from 1.6 +/- 0.1 ml/10 min to 3.4 +/- 0.2 ml/10 min. The increase in acid output caused by histamine was inhibited by the H2-antagonists cimetidine (3 mumole/kg) and ranitidine at 0.5 mumole/kg. Omeprazole (1.2 mumole/kg), an H-K-ATPase inhibitor, almost abolished acid output under both basal and histamine-stimulated conditions. Thus, the present method is simple and suitable to study the physiology and pharmacology of gastric secretion in the guinea pig with a particular emphasis on the action of histamine. Furthermore, because of the species involved, there is also a significant economical advantage and the guinea pig can also be used as a potential model for studying experimental ulcer.
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PMID:A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig. 331 43

Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K+-ATPase, is a potent and long-acting antisecretory drug. Because of its high potency and because of the possible risk of long-term hypergastrinaemia intermittent therapy with this drug may be preferable to continuous treatment in patients requiring long-term treatment. We have therefore studied the effect of weekly 3-day courses of 20 mg/day omeprazole followed by a 4-day period without medication (weekend therapy) for 4 weeks on basal and bombesin- (150 ng/kg.h) and pentagastrin- (1.5 micrograms/kg.h) stimulated gastric acid secretion in 10 normal subjects. Gastric acid was measured in week 1, before (day 1) and immediately after the 3-day omeprazole course (day 4), and further on day 6 and day 8, immediately before the next course, and at similar intervals in week 4 (days 22, 25, 27, and 29). When compared with pretreatment values, basal and bombesin- and pentagastrin-stimulated gastric acid were significantly (p less than 0.01-p less than 0.05) inhibited on the days immediately after the courses (days 4 and 25) but were, except for a significant (p less than 0.05) reduction of pentagastrin-stimulated gastric acid on day 8, not significantly affected on all other days. Basal and integrated bombesin-stimulated serum gastrin values were not significantly changed, whereas bombesin-stimulated peak serum gastrin was significantly (p less than 0.05) increased on days 22 and 29. Since this schedule of omeprazole induces pronounced, but transient, inhibition of gastric acid secretion without provoking marked hypergastrinaemia, intermittent weekend therapy may be suitable for long-term maintenance treatment with this drug.
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PMID:Effect of intermittent weekend therapy with omeprazole on basal and bombesin- and pentagastrin-stimulated gastric acid and serum gastrin. 338 Oct 63

The effectiveness of a single, morning oral dose of 40 mg omeprazole or a twice daily oral dose of 150 mg ranitidine was compared in a randomized endoscopically controlled double-blind trial at 37 clinics in Austria, Germany and Switzerland. A total of 178 out-patients in stages I-IVa (after Savary and Miller) were entered into the trial: 78 in stage I, 60 in stage II, 27 in stage III, and in 13 in stage IVa. As early as at the end of the third treatment week there was a significantly higher rate of complete healing or reduction into a lower stage with omeprazole than ranitidine (85% vs 67%; P less than 0.02). After six treatment weeks, healing tendency after omeprazole compared with ranitidine was 85% vs 45% (P less than 0.04). Omeprazole also brought earlier improvement in symptoms. The difference was statistically significant for heartburn (pyrosis): P less than 0.01. Both drugs were equally well tolerated and there were no clinically significant side-effects. This is the first demonstration that the ATPase inhibitor omeprazole is superior to the H2-receptor antagonist ranitidine in the treatment of reflux oesophagitis.
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PMID:[Different healing tendencies of reflux esophagitis following omeprazole and ranitidine. Results of a German-Austrian-Swiss multicenter study]. 351 Aug 47

The effect of gastric anacidity on the absorption of food-bound cobalamins is uncertain. Omeprazole, an inhibitor of the enzyme H-K-ATPase in the parietal cell, is the most potent inhibitor of gastric acidity known so far. In 17 healthy male volunteers the absorption of liver-bound cobalamins was assessed after a single intravenous dose of omeprazole (80 mg) or placebo in a double-blind, crossover manner. The effect of omeprazole on pH, gastric acidity, and intrinsic factor (IF) concentration was measured in aspirates of gastric juice 5 min before and 30 and 60 min after the administration of liver homogenate containing 0.74 nmol of 57Co-labelled cobalamins. Omeprazole treatment resulted in anacidity (pH values above 6.0) in 14 individuals 30 min after the liver dose and in 15 individuals after 60 min. The IF concentration was unchanged in the omeprazole experiment as compared with the placebo experiment. The absorption of liver-bound cobalamins was 310 pmol (189-501 pmol) in the omeprazole experiment as compared with 415 pmol (150-549 pmol) in the placebo experiment (median values and range, p = 0.5228). We suggest that anacidity induced by omeprazole does not reduce the absorption of liver-bound cobalamins.
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PMID:The effect of omeprazole on gastric acidity and the absorption of liver cobalamins. 357 26

It has been hypothesized that prolonged achlorhydria causes compensatory elevation of serum gastrin, and that there is an association in rats between sustained hypergastrinemia, hyperplasia of gastric enterochromaffin-like cells, and subsequent formation of gastric carcinoids in 2-year carcinogenicity studies. The present study examined whether daily administration of gastric antisecretory drugs in rats for 4 days could cause hypergastrinemia associated with inhibition of acid output. Rats were dosed orally for 4 days with the histamine H2-receptor antagonist ranitidine or the H+,K+-sensitive ATPase inhibitor omeprazole, and examined on day 5 for effects on gastric acid secretion and serum gastrin. Omeprazole (138 mg/kg/day significantly inhibited gastric acid secretion and increased serum gastrin levels. Large, single daily doses of ranitidine (1000-2000 mg/kg/day) had no effect on 24-hr acid or gastrin secretion; however, ranitidine did inhibit next-day acid secretion with associated increases in serum gastrin when administered in three divided doses. These results with ranitidine support the hypothesis that a sustained gastric antisecretory action will cause a compensatory hypergastrinemia, regardless of the antisecretory agent used. The ability to detect increased serum gastrin levels associated with inhibition of acid secretion, after administration of antisecretory agents for only 4 days, suggest that this short 5-day test may be useful for determining the potential of antisecretory agents to cause hypergastrinemia due to 24-hr inhibition of acid secretion and may be predictive of long-term hyperplastic changes.
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PMID:Use of a five-day test to predict the long-term effects of gastric antisecretory agents on serum gastrin in rats. 369 37

Omeprazole, a potent long-acting inhibitor of gastric acid secretion that exerts its inhibitory action by direct blocking of the H+, K+-adenosine triphosphatase in the parietal cells, was either applied topically to the solution bathing the exposed mucosa of the test rats or administered intravenously as a bolus injection. The superficial mucosal vessels were monitored on a television screen through a microscope and videorecorded for off-line analysis of red cell velocities and vessel diameters, from which blood flow was calculated. Intravenous omeprazole (5 or 10 mumol/kg) totally abolished the basal secretion 15-25 min after injection, with a parallel decrease in blood flow of approximately 25% for both doses. Omeprazole, 5 mumol/kg, given intravenously to rats stimulated with pentagastrin (20 micrograms/kg X h) significantly inhibited the stimulated acid output, but the blood flow was not significantly decreased. Topical application of omeprazole (2.5 mM in 6 ml) significantly increased blood flow (approximately 15%) while in contact with the mucosa both in the resting and in the pentagastrin (20 micrograms/kg X h)-stimulated situations. However, 10-20 min after the application period, blood flow was restored to the values before application of omeprazole and the acid output was significantly decreased. The results indicate that omeprazole exerts only minor influences on the gastric mucosal microcirculation in spite of its potent acid-inhibitory effect.
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PMID:Effects of omeprazole on gastric mucosal microcirculation and acid secretion in the rat. 381 93

Substituted benzimidazoles represent a new class of gastric secretory inhibitors, which suppress acid secretion via direct inhibition of the parietal cell H+/K+-ATPase. The most potent derivative so far is omeprazole, which inhibits basal acid secretion and prevents the stimulatory effect of all classical acid secretory stimulants. In man, a single dose of 80 mg leads to almost complete achlorhydria over 24 hours. The results of the first duodenal ulcer trial with omeprazole are encouraging. No definite side effects have been attributed to the drug so far. Omeprazole may possibly initiate a new era in the medical treatment of peptic ulcer disease.
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PMID:[Substituted benzimidazoles--a new dimension in ulcer therapy?]. 632 98

Twenty four hour intragastric acidity was measured in nine patients with duodenal ulcer before and after one week of treatment with oral omeprazole 30 mg daily, a drug that inhibits gastric secretion by inhibition of parietal cell H+K+ adenosinetriphosphatase (ATPase). Omeprazole virtually eliminated intragastric acidity in all patients: the median 24 hour intragastric pH rose from 1.4 to 5.3 and the mean hourly hydrogen ion activity fell from 38.50 to 1.95 mmol(mEq)/1 (p less than 0.001). This inhibition of 24 hour intragastric acidity is more profound than that previously reported with either cimetidine 1 g daily or ranitidine 300 mg daily.
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PMID:Effect of daily oral omeprazole on 24 hour intragastric acidity. 640 76


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