SCH 28080 is a lumenally acting, K+-site inhibitor of the gastric (H+ + K+)-ATPase.

摘要: SCH 28080 (2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile) is an effective inhibitor of acid secretion in vivo and a reversible, K+-competitive the gastric (H+ + K+)-ATPase vitro. The actions have been studied on vesicle preparations containing K+)-ATPase. At pH 7, inhibition was competitive with respect to K+ for both ATPase (Ki = 24 nM) pNPPase 275 activities. A close analogue (methylated 1-N position), that not expected cross membranes freely, inhibited activity less effectively intact preparations, where lumenal (extracellular) face membrane directly accessible. This suggested enzyme activities at site enzyme. Being protonatable weak base (pKa 5.6), would be accumulate lumenal, acidic side parietal cell its protonated form. potency 28080, relative “non-protonatable” analogue, increased low pH, commensurate proportion Thus accumulating form active inhibitory species. SCH (50 blocked rapid, K+-stimulated dephosphorylation catalytic phosphoenzyme intermediate room temperature. 4°, higher concentrations were required, suggesting rate binding slow temperatures.