Difference between Two Isozymes of (Na+ + K+)-ATPase in the Interaction with Omeprazole

Abstract

The difference in functional SH groups between two isozymes (α(+) and and α forms) of (Na++K+)-ATPase was examined using omeprazole, a hydrophobic drug which was reported to modify SH groups of gastric (H++K+)-ATPase. Omeprazole inhibited rat brain and kidney (Na++K+)-ATPase activities in a time- and dose-dependent manner, and it inhibited incorporation of [3H]NEM into the catalytic subunit of the enzymes. The inhibition was greater in the brain enzyme than in the kidney enzyme. The inhibition of the brain enzyme showed a lag time, whereas the kidney enzyme was inhibited according to pseudo-first order kinetics. The inhibition by omeprazole of Na+-dependent phosphorylation and K+-stimulated phosphatase activity in the brain enzyme preparation was parallel with that of the overall (Na++K+)-ATPase reaction, while the partial reactions of the kidney enzyme showed different sensitivities to inhibition by omeprazole. Furthermore, the inhibition by omeprazole of [3H]NEM reactivity in the brain α(+) form was greater in the presence of SDS than in the absence, whereas the inhibition in the brain and kidney α forms was less in the presence of SDS than in the absence. These findings suggest that the isozymes of (Na++K+)-ATPase differ in hydrophobicity of SH groups of their catalytic subunits.