Klaus Weidmann

Gastric H+/K+-ATPase inhibitors

Publisher Summary This chapter focuses on gastric H + /K + -ATPase inhibitors. The effect of gastric H + /K + -ATPase inhibitors on enzyme activity (ATP cleavage) can be studied in vitro with partly purified H + /K + -ATPase preparations. The assay has been used more effectively to study the mechanism of action of H + /K + -ATPase inhibitors in detail than to study the structure-activity relationship of such inhibitors. Since H + /K + -ATPase inhibitors of the omeprazole-type need acid activation and the enzyme assay should be performed at neutral pH values, a pre-incubation period at the lowest possible pH of about 6 is used to initiate the acidic conversion of the test compound into its active principle. This reflects more the chemical instability of the test compound at neutral pH values than its effect during conditions of much higher acidity within the secretory cannaliculus of the parietal cell during acid secretion. Many chemically labile inhibitors are, therefore, very active in this test system. Proton transport studies in intact gastric vesicles, which form a pH gradient similar to in vivo conditions , are more suitable for studying the mechanism of action, acid-conversion and structure-activity relationship of H + /K + -ATPase inhibitors.