Actions of antisecretory agents on proton transport in hog gastric microsomes.
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 Mg2+, 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, spermine, and NaSCN, but not by cimetidine, prostaglandin E2, 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 omeprazole inhibits H+ accumulation by inhibiting K+-ATPase, fenoctimine suppresses H+ accumulation mainly by increasing the loss of accumulated H+ from the microsomal vesicles, spermine and NaSCN reduce H+ accumulation by inhibiting the transport of H+ into microsomal vesicles.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D004058:Diffusion; D005753:Gastric Mucosa / Q000201:enzymology / Q000648:ultrastructure*; D017506:H(+)-K(+)-Exchanging ATPase; D008274:Magnesium / Q000494:pharmacology; D008854:Microscopy, Electron; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013552:Swine; D014634:Valinomycin / Q000494:pharmacology
D010880:Piperidines; D014634:Valinomycin; D013096:Spermine; C037813:fenoctimine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D008274:Magnesium; D012966:Sodium Cyanide; D011188:Potassium