Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Omeprazole is a new hydrogen-potassium adenosine triphosphatase antagonist with indications for severe reflux esophagitis and Zollinger-Ellison syndrome. Side effects involving the liver have consisted of minimal elevations of hepatocellular enzymes with higher dosages. We present what we believe is the first reported case of fulminant hepatic failure related to omeprazole.
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PMID:Fulminant hepatic failure related to omeprazole. 155 42

We tested the hypothesis that the gastric H+/K+ adenosine triphosphatase inhibitor, omeprazole, because of its different mode of action and pronounced inhibitory effect on gastric acid secretion, may be more effective in peptic ulcer that is refractory to histamine H2 receptor antagonist treatment than continuing the same therapy. Altogether 107 patients (duodenal ulcer, n = 88; prepyloric ulcer, n = 14; gastric ulcer, n = 3; mixed sites, n = 2) with refractory peptic ulcer - that is ulcer unhealed after at least two months' treatment with cimetidine 0.8 g or 1 g daily or with ranitidine 0.3 g daily - were randomly allocated to receive either omeprazole 40 mg daily (n = 54) or to continue treatment with the same H2 receptor antagonist and at the same dose (n = 53) for up to eight weeks. The patients in the two treatment groups were well matched demographically. Healing by 'intent to treat' analysis was as follows: at four weeks, omeprazole 46 of 54 (85%), H2 receptor antagonist 18 of 53 (34%) (p less than 0.0001); and at eight weeks, 52 of 54 (96%) and 30 of 53 (57%) respectively (p less than 0.0001). One patient was lost to follow up but of the 22 patients whose ulcers were shown to be unhealed at endoscopy after receiving continued H2 receptor antagonist treatment, 21 healed in four to eight weeks when changed to omeprazole. Daytime epigastric pain cleared at four weeks in 43 of 47 (91%) patients on omeprazole and in 32 of 46 (70%) on H2 receptor antagonists (p=0.01) and relief of all dyspeptic symptoms occurred in 39 of 47 (83%) and 23 of 45 (51%) (p=0.0009) patients respectively. Adverse events occurred in 11 of 54 (20%) patients on omeprazole and in 12 of 35 (34%) on cimetidine but in none on ranitidine. The events were mild and none required treatment withdrawal. The commonest event in patients on omeprazole was loose stools or diarrhoea (n=5). Omeprazole was significantly better than continued H2 receptor antagonist treatment for the short term management of refractory peptic ulcer as judged by healing rate and pain relief, and it was safe.
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PMID:Treatment of refractory peptic ulcer with omeprazole or continued H2 receptor antagonists: a controlled clinical trial. 162 76

Omeprazole, a potent inhibitor of gastric hydrogen ion transporting, potassium-stimulated adenosine triphosphatase, was found to be transformed into an SH-reactive strong fluorescent molecule (excitation and emission wavelengths of 370 and 560 nm, respectively) in an acidic medium. The addition of glutathione- or protein-containing sulfhydryl groups such as pepsin to the medium decreased the fluorescence. Also, the increase in the pH of the medium decreased the fluorescence. The fluorescent molecule was identified to be an acid-activated planar cyclic sulfenamide derivative of omeprazole. The transformation was studied in H+-preaccumulated hog gastric vesicles, which contain the hydrogen ion transporting, potassium-stimulated adenosine triphosphatase. The addition of omeprazole to the vesicle suspension induced a rapid increase in the fluorescence intensity, indicating that omeprazole was activated in the intravesicular space. Then, the intensity biphasically decreased with time. The slower small decrease was due to the reaction of the sulfenamide with sulfhydryl group(s) located on the acid secretory side of the hydrogen ion transporting, potassium-stimulated adenosine triphosphatase. Omeprazole was also activated in the acidic lumina of isolated rabbit gastric glands that were stimulated with histamine. Furthermore, direct evidence was obtained from the imaging of the fluorescence that omeprazole was activated in the acidic compartments of the isolated Xenopus oxyntic cell.
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PMID:Acid activation of omeprazole in isolated gastric vesicles, oxyntic cells, and gastric glands. 254 Oct 41

Omeprazole is the first H+-K+-adenosine triphosphatase antagonist available for clinical use. It has a very strong, long-lasting inhibitory effect on gastric acid secretion. The effect is very selective: pepsin and intrinsic factor secretion are unaffected. Once-daily doses of 30-40 mg cause a more than 95% reduction of intragastric acidity. Lower doses have less predictable results. During treatment with omeprazole serum gastrin levels increase. After cessation of treatment gastric acid secretion and serum gastrin levels rapidly return to pretreatment levels. No rebound phenomena are observed after treatment.
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PMID:Effects of omeprazole on gastric secretory functions. 269 7

Due to its potent and long-lasting antisecretory properties is omeprazole, the first clinically used H+/K+-adenosine triphosphatase inhibitor, highly effective in healing of duodenal and gastric ulcers and reflux oesophagitis. Omeprazole is superior to all other presently available antiulcer drugs in the treatment of Zollinger-Ellison syndrome and refractory ulcers. Short-term administration of the drug is safe. However, serum gastrin and gastric enterochromaffin-like cells should be carefully monitored during long-term treatment with the drug.
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PMID:H+/K+-adenosine triphosphatase inhibitors. A new approach to the treatment of acid-peptic diseases. 269 16

The results reported in this paper indicate that representative H2-receptor antagonists are capable of maximally inhibiting gastric acid secretion in animals under the two general circumstances in which it occurs physiologically. Interdigestive or basal secretion was examined in chronic gastric fistula rats and food-stimulated secretion in vagally innervated, lesser curvature pouch dogs. The H2 antagonists studied and omeprazole, an inhibitor of the proton pump H+, K+-adenosine triphosphatase, also decreased pepsin secretion in rats, although not to the same maximal degree as acid secretion. Gastric emptying was increased by each H2 antagonist but only at high acid inhibitory doses. Omeprazole, in contrast, did not alter gastric emptying at a similar antisecretory dosage level. In dogs, a representative H2-receptor antagonist markedly inhibited food-stimulated acid secretion. These data suggest that the predominant effect of omeprazole and H2-receptor antagonists upon gastric function is to inhibit acid secretion and that H2-receptor antagonists may be capable of maximally inhibiting endogenous acid secretion in humans, as does omeprazole, if given under proper conditions.
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PMID:Effects of H2-receptor antagonists upon physiological acid secretory states in animals. 285 83

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of omeprazole are reviewed. Omeprazole, a substituted benzimidazole, has a unique site and mechanism of action because it inhibits the proton pump--i.e., hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase)--and consequently blocks the final common step in the gastric acid secretory pathway. Omeprazole inhibits basal and histamine-, gastrin- and pentagastrin-stimulated gastric hydrochloric acid secretion. It produces a dose-dependent reduction in gastric acidity, gastric acid output, and gastric juice volume and has variable effects on pepsin secretion. Omeprazole has no documented effect on esophageal motility or lower esophageal sphincter pressure. Omeprazole is variably absorbed from the gastrointestinal tract, and food appears to decrease the rate, but not the extent, of drug absorption. The drug is approximately 95% bound to plasma proteins and is metabolized to inactive components that are enterohepatically or renally eliminated. Omeprazole is more effective (in most studies) than H2-receptor antagonists in treating duodenal ulcer, at least as effective in treating benign gastric ulcer, and more effective in treating reflux esophagitis. Omeprazole has been used successfully in patients with Zollinger-Ellison syndrome refractory to treatment with H2-receptor antagonists. Gastrointestinal complaints (nausea and diarrhea) are the most commonly reported adverse effects associated with omeprazole therapy. The most frequently reported laboratory abnormality occurring with omeprazole use is elevation of serum aspartate aminotransferase and alanine aminotransferase concentrations. Omeprazole will serve a valuable role in the management of gastrointestinal tract ulcers and hypersecretory conditions.
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PMID:Therapeutic evaluation of omeprazole. 306 85

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

Proton pump inhibitors irreversibly inhibit the enzyme hydrogen-potassium adenosine triphosphatase (H(+)-K(+)-ATPase), which suppresses acid production in the parietal cell of the stomach. Omeprazole, the prototype proton pump inhibitor, has proved to be very effective. However, newer agents are being designed to provide even more potent acid suppression and longer-acting proton pump inhibition, with the goal of further controlling gastric hypersecretion. Lansoprazole is the second proton pump inhibitor available on the market. Pantoprazole is not yet available for general use in the United States. However, each of these drugs is slightly different from omeprazole, thus offering some possible clinical advantages. Compared with omeprazole, lansoprazole has a longer duration of action and improved activity against Helicobacter pylori, while pantoprazole has less interaction with the cytochrome P-450 system and more predictable bioavailability. All three agents have similarly high healing rates for acid peptic diseases and appear to be superior to histamine2-receptor antagonists.
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PMID:Proton pump inhibitors: new drugs and indications. 854 54

Omeprazole and pantoprazole are known to be irreversible, SH-acting inhibitors of gastric H+,K+-adenosine triphosphatase (H+,K+-ATPase). Both drugs concentration-dependently and pH-dependently inhibited K+-dependent p-nitrophenyl phosphatase (K+-pNPPase) activity in purified rabbit gastric microsomes. The potency of omeprazole was about three times that of pantoprazole in the pH ranges tested. Both drugs also inhibited acid secretion, as determined by [14C]aminopyrine accumulation in isolated rabbit gastric glands, with the potency ratio being about 5 (omeprazole over that of pantoprazole). Under conditions in which acid secretion was inhibited completely by the drugs, the total K+-pNPPase activity in the digitonin-permeabilized glands was scarcely reduced, showing an apparent discrepancy between the acid secretion and the proton pump activity. The isolated glands were stimulated with secretagogues for 30 min in the presence of the inhibitors, homogenized, and then separated into fractions in which K+-pNPPase activity was measured. Omeprazole exclusively inhibited the activity in the low-speed fraction, which was rich in the apical membranes, whereas pantoprazole did not inhibit activity in any fraction. When the time of treatment with the inhibitors was increased up to 5 hr, the inhibition of the total K+-pNPPase activity in the glands reached a plateau at an inhibition rate lower than 50% within 2 hr. This suggested that no continuous recycling of the proton pump was occurring during stimulation. The inhibitory effect of both drugs on the permeabilized gland preparation was less potent than that on the purified enzyme, especially at the higher pH, and it appeared to be partially reversible. The extent of the reduction in potency was more prominent for pantoprazole. It is concluded that a lower amount of proton pump activity needs to be inhibited by pantoprazole than by omeprazole to achieve the same extent of acid secretion inhibition. This appears to be due to the nature of pantoprazole, i.e. the requirement of low pH for activation and the partial reversibility of the inhibition.
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PMID:Correlation between acid secretion and proton pump activity during inhibition by the proton pump inhibitors omeprazole and pantoprazole. 1048 39


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