A new concept regarding the mechanism of action of omeprazole.

OBJECTIVES

In this paper we investigated in humans and in animals the in vitro and in vivo effect of omeprazole upon purified and erythrocyte carbonic anhydrase (CA) I and II isozymes, as well as on gastric mucosa CA IV.

METHOD: In vitro, we observed the effect of omeprazole at concentrations between 10(-8)-10(-4) M on purified CA I and CA II, and also on isolated gastric mucosa CA IV, renal and pulmonary CA IV activity, using the dose-response relationship. In vivo, we studied the effect of omeprazole (Losec) on gastric CA I, II and IV, as well as on erythrocyte CA I and CA II, in humans and in animals.

RESULTS

In vitro omeprazole inhibits pH-dependent purified CA I and CA II and gastric mucosa CA IV according to dose-response relationship. In vivo, the i.v. administration of omeprazole in rabbits and in humans shows a decrease of erythrocyte CA I and CA II activity as well as of gastric mucosa CA I, II and IV.

CONCLUSIONS

Omeprazole in its active form (sulfenamide) selectively inhibits gastric mucosa CA IV and does not modify the activity of the same isozyme from the kidney and lung proving that the enzyme has an organ specificity. Our results lead to the conclusion that omeprazole possesses a dual mechanism of action: both H+K+ATPase and CA inhibition--enzymes that could be in a functional coupling. This dual mechanism of action might explain the higher effectiveness of treatment using substituted benzimidazole inhibitors compared to other therapies.