Inhibition of the gastric (H + + K +)-ATPase by fenoctimine

Abstract

The effects of fenoctimine, an inhibitor of gastric acid secretion, on the microsomal (H + + K +)-ATPase were studied. In the micromolar concentration range, fenoctimine inhibited hydrolysis of ATP and π-nitrophenyl phosphate by the (H + + K +)-ATPase. Inhibition was reversible and non-competitive with substrate. The apparent K i was dependent on the concentration of membranes, being increased by added liposomes or high microsomal membrane concentrations. Over the concentration range that (H + + K +)-ATPase was inhibited, fenoctimine increased by the turbidity of microsomal suspensions. The effects of fenoctimine were not specific for the gastric (H + + K +)-ATPase, since the hydrolytic activities of the (Na + + K +)-ATPase and mitochondrial ATPase were also inhibited by the drug. These results suggest that inhibition of hydrolysis may not be the direct result of an interaction between the (H + + K +-ATPase and fenoctimine but the secondary effect of a fenoctimine-induced perturbation of the microsomal membrane.