Actions of antisecretory agents on proton transport in hog gastric microsomes

Abstract

The properties of K +-stimulated ATP hydrolysis (K +-ATPase) and vesicular accumulation of H + (H + accumulation) in hog gastric microsomes were investigated. The microsomes consisted of smooth surfaced vesicular particles, 70–300 nm in diameter. Both the activities of ATPase and the vesicular accumulation of H + were stimulated by K + in the presence of Mg 2+, and enhanced by the K +-ionophore, valinomycin. However, there were differences in regulation of K +-ATPase and H + accumulation by K + ions, i.e. K + at concentrations higher than 10 mM decreased K +-ATPase activity but further enhanced H + transport. This observation suggests that the two reactions are partly independent. The H + accumulation was inhibited by omeprazole, fenoctimine, spennine, and NaSCN, but not by cimetidine, prostaglandin E 2, and atropine. The inhibitory effect of omeprazole on H + accumulation paralleled the inhibition of k +-ATPase, while fenoctimine, spermine, and NaSCN suppressed H + accumulation, without inhibiting K +-ATPase, under appropriate concentrations. In addition, the spontaneous diffusion of H + across the microsomal membrane was markedly enhanced by fenoctimine, but not by the other agents used. These results indicate that (1) omeprazole inhibits H + accumulation by inhibiting K +-ATPase, (2) fenoctimine suppresses H + accumulation mainly by increasing the loss of accumulated H + from the microsomal vesicles, (3) spermine and NaSCN reduce H + accumulation by inhibiting the transport of H + into microsomal vesicles.