title: Inhibition of partially purified K+/H+-ATPase from guinea-pig isolated and enriched parietal cells by substituted benzimidazoles.
abstract: The cellular and subcellular distributions of adenosinetriphosphatases (ATPases) were examined in guinea-pig gastric mucosal cells. All cell types displayed Mg2+-ATPase and bicarbonate (HCO3-)-stimulated ATPase activity. K+-ATPase was located only in fractions derived from parietal cells. Differential and density-gradient centrifugation of material prepared from parietal cells revealed that K+-ATPase activity was located in a tubulo-vesicular membrane fraction. Enzyme activity was ten fold greater in this fraction than in a crude parietal cell homogenate. The substituted benzimidazoles, omeprazole and picoprazole, inhibited K+-ATPase (IC50 1.8 +/- 0.5 mumol l-1 and 3.1 +/- 0.4 mumol l-1, respectively). Detailed kinetic analysis indicated that these compounds were non-competitive and reversible inhibitors of the enzyme. In contrast cimetidine and verapamil were without effect on the enzyme. The relevance of the inhibition of K+-ATPase to the antisecretory activity of the benzimidazoles, in experimental animals and man, is discussed.
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase; D027682:Cation Transport Proteins; D002458:Cell Fractionation; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D007700:Kinetics; D008297:Male; D009853:Omeprazole; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; C022761:potassium transporting ATPase; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; C028887:picoprazole