title: Gastric H+,K(+)-ATPase as a therapeutic target in peptic ulcer disease.
abstract: The presence of unbuffered acid appears to be an essential contributory factor in the pathogenesis of peptic ulcer disease. Treatment has concentrated therefore on the reduction of acidity, and the last decade has seen the widespread and effective use of H2 antagonists. They are, at low doses, more successful in improving the natural history of duodenal ulcer disease than of gastric or esophageal ulceration. The H2 receptor plays a central role in activation of parietal cell acid secretion, and antagonists at this receptor block most (but not all) of the acid secretion due to even gastrinergic or muscarinic (vagal) stimulation. In hypergastrinemic states such as Zollinger-Ellison syndrome, or where acid secretion has to be inhibited by more than 20% over a 24-hr period, such as for treatment of esophagitis, NSAID damage, or gastric ulcers, the dose and frequency of administration of the currently available antagonists must be increased to achieve reliable therapy. This has led to a search for an alternative target for acid inhibitory drugs, such as the gastric acid pump, the H+,K(+)-ATPase. This article focuses on the function of this ATPase and suggests that inhibition of this pump will provide a more efficacious means of reduction of acid secretion by the stomach, hence improving and simplifying therapy of acid related diseases.
authors.affiliation: CURE, UCLA.
authors.forename: G
authors.initials: G
authors.lastname: Sachs
authors.forename: K
authors.initials: K
authors.lastname: Munson
authors.forename: K
authors.initials: K
authors.lastname: Hall
authors.forename: S J
authors.initials: SJ
authors.lastname: Hersey
mesh_terms: D000818:Animals; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase