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)

When 17 macrocyclic lactone antibiotics were examined for their abilities to inhibit gastric H+,K(+)-ATPase, copiamycin A was found to have the strongest and relatively specific activity with IC50s of 15.7 micrograms/ml and greater than 100 micrograms/ml against the hog gastric H+,K(+)-ATPase and the dog kidney Na+,K(+)-ATPase, respectively. Furthermore, this antibiotic inhibited the histamine-induced gastric acid secretion in the isolated gastric mucosal membrane of guinea pigs and the gastric ulcer formation in pylorus-ligated rats.
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PMID:Inhibitory effects of copiamycin A, a macrocyclic lactone antibiotic, on gastric H+,K(+)-ATPase, acid secretion and ulcer formation. 164 41

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 is the first of a new class of gastric antisecretory drugs, proton pump inhibitors. It inhibits the H+,K(+)-adenosinetriphosphatase enzyme of the gastric parietal cell, resulting in potent, long-lasting suppression of basal and stimulated acid secretion. The drug is currently approved for treatment of gastroesophageal reflux disease and Zollinger-Ellison syndrome. In clinical trials, treatment with omeprazole results in rapid healing of duodenal ulcers; it is also effective in treating gastric ulcer disease. It is uniformly well tolerated without significant adverse effects, although animal studies linked profound long-term suppression of gastric acid secretion with the development of gastric carcinoids. Potential future uses include the prophylaxis of ulceration secondary to stress or use of nonsteroidal anti-inflammatory drugs, and the prophylaxis of recurrent peptic ulcer disease.
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PMID:Omeprazole: a new drug for the treatment of acid-peptic diseases. 193 56

Omeprazole is a specific inhibitor of H+,K(+)-ATPase or 'proton pump' in parietal cells. This enzyme is responsible for the final step in the process of acid secretion; omeprazole blocks acid secretion in response to all stimuli. Single doses produce dose-dependent inhibition with increasing effect over the first few days, reaching a maximum after about 5 days. Doses of omeprazole 20mg daily or greater are able to virtually abolish intragastric acidity in most individuals, although lower doses have a much more variable effect. Omeprazole causes a dose-dependent increase in gastrin levels. Omeprazole must be protected from intragastric acid when given orally, and is therefore administered as encapsulated enteric-coated granules. Absorption can be erratic but is generally rapid, and initially the drug is widely distributed. It is highly protein-bound and extensively metabolised. Its elimination half-life is about 1h but its pharmacological effect lasts much longer, since it is preferentially concentrated in parietal cells where it forms a covalent linkage with H+,K(+)-ATPase, which it irreversibly inhibits. Omeprazole binds to hepatic cytochrome P450 and inhibits oxidative metabolism of some drugs, the most important being phenytoin. Omeprazole has produced short term healing rates superior to the histamine H2-receptor antagonists in duodenal ulcer, gastric ulcer and reflux oesophagitis. It has also been shown to be highly effective in healing ulcers which have failed to respond to H2-receptor antagonists, and has been extremely valuable in treating patients with Zollinger-Ellison syndrome.
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PMID:Clinical pharmacology of omeprazole. 202 1

A series of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinolin es was synthesized and examined for their (H+ + K+)adenosine triphosphatase (ATPase)-inhibitory and antisecretory activities against histamine-induced gastric acid secretion in rats. Many compounds tested were potent inhibitors of (H+ + K+)ATPase. Most compounds showed antisecretory activity. The antiulcer activity against water-immersion stress-induced gastric ulcer, aspirin-induced gastric ulcer and gastric necrosis induced by hydrochloric acid also were tested in the rat. Some of these compounds, in particular, 4-(N-allyl-N-methylamino)-1-ethyl-8-[(5-fluoro-6-methoxy-2-benzimidazoly l) sulfinylmethyl]-1-ethyl-1,2,3,4-tetrahydroquinoline (XVIIx) were found to have potent activity. The structure-activity relationships are discussed.
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PMID:Synthesis and antiulcer activity of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinoli nes and related compounds. 217 36

The H+K+-ATPase is supposed to be the terminal step in the acid-secreting pathway in the parietal cell. Omeprazole blocks this enzyme, resulting in a marked inhibition of basal and stimulated acid secretion. With omeprazole 20 mg daily, 24-hour intragastric acidity is decreased by about 90%. Several clinical studies have now been published in which omeprazole has been compared with the H2-receptor antagonists cimetidine and ranitidine. Omeprazole in doses between 20 and 40 mg daily resulted in healing rates between 65% and 82% after treatment for 2 weeks and between 90% and 100% after treatment for 4 weeks. Treatment with omeprazole also gave faster and more pronounced pain relief. One comparative study in gastric ulcer has also been published showing healing rates equal to those with ranitidine. Placebo-controlled trials have also shown very pronounced therapeutic effect in reflux esophagitis. Omeprazole seems to be the drug of choice in Zollinger-Ellison syndrome, giving beneficial clinical effects and pronounced and long-lasting reduction in gastric acid secretion.
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PMID:Clinical perspectives of drugs inhibiting acid secretion--H+K+-ATPase inhibitors. 302 57

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

Gastric ulcerations induced in rats by a combination of indomethacin and cold-stress (5 +/- 1 degrees C) for 6 hr were more severe than those induced by indomethacin or cold-stress alone. The acidity of gastric juice was increased in rats treated with indomethacin plus cold-stressed. Histamine H2 receptor antagonists, (H+-K+) ATPase inhibitors and prostaglandins inhibited gastric ulcer formation in indomethacin plus cold-stress treated rats, whereas anticholinergics aggravated the ulceration. The indomethacin plus cold-stress induced acid secretion was inhibited by cimetidine and omeprazole in pylorus-ligated rats. Atropine had less effect on the increase in acidity than cimetidine and omeprazole. These findings indicate that the ulcer formation in indomethacin plus cold-stress treated rats is related the increased in acidity of gastric juice. This gastric ulcer model may be useful for evaluating antiulcer agents.
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PMID:Effects of indomethacin and cold-stress on gastric acid secretion and ulceration. The effects of anti-acid secretory agents in rats. 367 83

Gastric ulcer was elicited in rats by reserpine (5 mg x kg-1 sc.) administration. Ulcer formation (number and severity) was measured 6, 12, 18 and 24 hr after reserpine administration. At the time of killing of the animals, tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP) were measured enzymatically and by radioimmunoassay in the gastric fundal mucosa. The sum of ATP + ADP + AMP (adenylate pool) and the ratio of ATP x ADP-1 were calculated. It was found that (1) the tissue levels of ATP, AMP, cAMP, sum of ATP / ADP + AMP (adenylate pool) and ratio of ATP x ADP-1 increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, thereafter these values decreased gradually and significantly; (2) the tissue level of ADP increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, meanwhile its level increased significantly at 18 and 24 hr; (3) the value of energy charge (ATP + 0.5 ADP x ATP + ADP + AMP-1) remained unchanged; (4) the peaks of biochemical alterations in the gastric fundus mucosa preceded he appearance of ulcers. It was concluded that (1) reserpine ulcer appears after an active metabolic response in the rat gastric fundal mucosa; (2) hypoxaemic damage in the gastric fundal mucosa can be excluded as a possible underlying mechanism of ulcer formation produced by reserpine administration; (3) before the appearance of reserpine ulcer, significant changes in the feedback mechanism, system, i.e. between the ATP--membrane ATPase--ADP and the ATP--adenylate cyclase--cAMP energy systems, can be observed in the rat gastric fundal mucosa.
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PMID:Cellular energy systems and reserpine ulcer in rats. 632 19

Helicobacter pylori is a major cause of gastritis and an important factor in duodenal ulcer relapse. Eradication of H. pylori has usually been achieved by triple therapy, a combination of bismuth salts and two antibiotics. The disadvantage of these regimens is the large number of tablets and the high incidence of side effects. A new H+,K(+)-ATPase inhibitor, lansoprazole (LPZ), has a strong acid inhibitory effect and an anti-H. pylori effect in vitro. These dual effects have an advantage for the eradication of H. pylori by LPZ alone or by a combination of LPZ and antibiotics. In this study, we investigated an anti-H. pylori effect of LPZ alone and LPZ plus low-dose amoxicillin and the relation between the status of H. pylori colonization and the endoscopic healing stage. LPZ monotherapy suppressed H. pylori but did not eradicate it. LPZ plus low-dose amoxicillin dual therapy eradicated H. pylori in 45.5% of patients with gastric ulcer disease. However, this rate is not satisfactory for eradication therapy. The optimal dosage and duration of treatment need to be specified. A high rate of healing to the endoscopic S2 stage was achieved by eradication of H. pylori and the recurrence of gastric ulcer was suppressed in patients in whom H. pylori was eradicated. The eradication of H. pylori may change the natural course of gastric ulcer disease as it does in duodenal ulcer disease.
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PMID:Lansoprazole versus lansoprazole plus amoxicillin treatment for eradication of Helicobacter pylori in patients with gastric ulcer. 759 22


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