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  • Title: Omeprazole has a dual mechanism of action: it inhibits both H(+)K(+)ATPase and gastric mucosa carbonic anhydrase enzyme in humans (in vitro and in vivo experiments).
    Author: Puscas I, Coltau M, Baican M, Domuta G.
    Journal: J Pharmacol Exp Ther; 1999 Aug; 290(2):530-4. PubMed ID: 10411559.
    Abstract:
    In this study our experiments followed in vitro and in vivo the effect of omeprazole on purified and erythrocyte carbonic anhydrase (CA) I and II isozymes, as well as on gastric mucosa CA IV in humans. Our in vitro results show that omeprazole-induced inhibition of purified CA I and CA II and gastric mucosa CA IV is dose- and pH-dependent. In vivo, the i.v. administration of omeprazole in humans in therapeutic doses produced a decrease in erythrocyte CA I and CA II activity, as well as in gastric mucosa CA I, II, and IV. Regarding CA IV, the results lead to the conclusion that omeprazole selectively inhibits gastric mucosa CA IV and does not modify the activity of the same isozyme from the kidney and lung, indicating organ specificity. Our results strongly suggest that omeprazole has a dual mechanism of action: H(+)K(+)ATPase inhibition and gastric mucosa CA inhibition, and that these enzymes may be functionally coupled. This 2-fold mechanism of action could explain the greater effectiveness of substituted benzimidazoles as compared with other therapies.
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