Irreversible inactivation of rat gastric (H+-K+)-ATPase in vivo by omeprazole.

Subcutaneous administration of omeprazole, a gastric antisecretory agent belonging to the family of substituted benzimidazoles, brought about a dose-dependent decrease in gastric mucosal (H+-K+)-ATPase activity in the rat. The dose which inhibited 50% of the enzyme activity was 1 mg/kg from dose-response profiles obtained 3 h after the drug dosing. Duration profiles of the drug at 10 mg/kg showed that its ATPase-inhibitory effect reached the maximum in 2 h with 80% reduction of the enzyme activity. The gastric mucosal level of the ATPase activity remained to be maximally inhibited for 12 h and returned to a normal level with a half time of about 20 h. The return of the enzyme activity, however, was blocked by treatment with cycloheximide, an inhibitor of protein synthesis. These observations indicate that omeprazole irreversibly inactivates gastric (H+-K+)-ATPase in vivo.