What dual-action agents reveal about acid secretion: a combined experimental and modeling analysis.
A previously described simple mathematical model for gastric acid secretion is employed to characterize the acid secretion response to thiocyanate and omeprazole, two partially conservative inhibitors that inhibit both the formation and translocation of acid. In addition, the effect of dithiothreitol on the omeprazole inhibition was investigated. The model parameters were estimated from four data sets by a non-linear least squares procedure: a dynamic (time-dependent) set, made up of individual acid secretion rate curves; and three integral (time-independent) sets consisting of the curves of acid secreted and suppressed above and below baseline, respectively, and the index of conservation, all three as functions of agent exposure. At the translocation step the inhibition function was the same for the two inhibitors, and though similar at the formation step, they differ in that a Hill coefficient larger than unity is necessary in the thiocyanate inhibition function of the acid formation. Dithiothreitol protects only the formation step from inhibition by omeprazole. Hence, the binding sites for omeprazole are different for formation and translocation. This study exemplifies a non-invasive method for the investigation of the mechanism of gastric acid secretion following perturbation by external agents.
Licko
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Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Ekblad
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D000818:Animals; D001001:Anura; D001665:Binding Sites; D004229:Dithiothreitol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008954:Models, Biological; D009853:Omeprazole / Q000378:metabolism / Q000494:pharmacology*; D013861:Thiocyanates / Q000494:pharmacology*
D013861:Thiocyanates; D009853:Omeprazole; D004229:Dithiothreitol