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)

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

Kidneys of full-term newborn humans and animals conserve potassium (K+), a condition essential for growth. The cortical collecting duct (CCD) is uniquely adapted to accomplish this task early in life. CCDs isolated from newborn rabbits and microperfused in vitro show no net K+ secretion until after the third week of life; in contrast, segments isolated from adult animals secrete net K+ at high rates. The magnitude and direction of net K+ transport in the CCD reflect the balance of opposing fluxes of K+ secretion and K+ absorption mediated by principal and intercalated cells, respectively. The absence of net K+ secretion in the CCD early in life may thus be caused by a limited capacity of principal cells for K+ secretion and/or an excess of K+ absorption by intercalated cells. Recent studies provide data to support both possibilities. Patch-clamp analysis detects few conducting apical K+-secretory channels in neonatal principal cells, whereas fluorescent functional assays identify significant activity of the apical hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase), a pump that reabsorbs K+ in exchange for H+s, in adjacent intercalated cells. Under conditions prevailing in vivo, the sum of the fluxes mediated by these two cell types likely contributes to the relative K+ retention characteristic of the neonatal kidney.
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PMID:Regulation of potassium transport in the maturing kidney. 1019 48

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

Blockade of the gastric acid pump, hydrogen-potassium adenosine triphosphatase (H+,K+-ATPase), by proton pump inhibitors (PPIs) is one of the most effective treatments for gastro-oesophageal reflux disease (GORD). In ideal terms, however, the inhibition of acid secretion should occur rapidly, on the first dose, and remain virtually complete in a dose-dependent manner. Several aspects of PPI biochemistry prevent the achievement of this ideal. PPIs target the final step of acid secretion and, due to the covalent nature of their inhibition of H+,K+-ATPase, cause suppression of acid secretion long after the drug has been eliminated. Their disadvantages stem from their mechanism of action: they require accumulation and activation in active parietal cells and have short plasma half-lives, hence a relatively slow onset of action. An extension of PPI plasma half-lives is an obvious goal, possibly via exploitation of probable differences in the metabolism of the two enantiomers (structural mirror images) present in current PPI formulations: e.g., clinical data on the S-enantiomer of omeprazole (esomeprazole) suggest some improvement in acid control. An alternative is to generate a pro-drug of a PPI; plasma levels of the PPI would thus depend on release of the active metabolite from the pro-drug, again extending drug half-life. Another area of active investigation is the development of acid-pump antagonists to inhibit acid secretion at its final step.
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PMID:Improving on PPI-based therapy of GORD. 1143 May 7