A new concept regarding the mechanism of action of omeprazole

Objectives: In this paper we investigated in humans and in animals the in v itro and in vivo effect of omeprazole upon purified and erythrocyte carboni c anhydrase (CA) I and II: isozymes, as well as on gastric mucosa CA IV. Me thod: In vitro, we observed the effect of omeprazole at concentrations betw een 10(-8) - 10(-4) M on purified CA I and CA II, and also on isolated gast ric mucosa CA IV, renal and pulmonary CA IV activity, using the dose-respon se relationship. In vivo, we studied the effect of omeprazole (Losec) on ga stric CA I, II and IV as well as on erythrocyte CA I and CA II, in humans a nd in animals. Results: In vitro omeprazole inhibits pH-dependent purified CA I and CA II and gastric mucosa CA IV according to dose-response relation ship. In vivo, the i.v. administration of omeprazole in rabbits and in huma ns shows a decrease of erythrocyte CA I and CA II activity as well as of ga stric mucosa CA I, II and IV. Conclusions: Omeprazole in its active form (s ulfenamide) selectively inhibits gastric mucosa CA IV and does not modify t he activity of the same isozyme from the kidney and lung proving that the e nzyme has an organ specificity. Our results lead to the conclusion that ome prazole possesses a dual mechanism of action: both H(+)K(+)ATPase and CA in hibition - enzymes that could be in a functional coupling. This dual mechan ism of action might explain the higher effectiveness of treatment using sub stituted benzimidazole inhibitors compared to other therapies.