Inhibition of partially purified K/H+ ‐ATPase from guinea‐pig isolated and enriched parietal cells by substituted benzimidazoles

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Abstract
1 The cellular and subcellular distributions of adenosinetriphosphatases (ATPases) were examined in guinea-pig gastric mucosal cells. All cell types displayed Mg2+-ATPase and bicarbonate (HCO&3bar;)-stimulated ATPase activity. K+-ATPase was located only in fractions derived from parietal cells. 2 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. 3 The substituted benzimidazoles, omeprazole and picoprazole, inhibited K+-ATPase (IC50 1.8 ± 0.5 μmol 1−1 and 3.1 ± 0.4 μmol 1−1, 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. 4 The relevance of the inhibition of K+-ATPase to the antisecretory activity of the benzimidazoles, in experimental animals and man, is discussed.