Activation of rat gastric mucosal adenylyl cyclase by secretory inhibitors

Abstract

Prostaglandin (PG) E1, E2, A1, and A2 stimulated rat gastric corpus mucosal membrane adenylyl cyclase activity. PGE1 (Kalpha congruent to 8 muM) affected the maximum velocity but not the affinity of the enzyme for ATP and maximum PGE1 activation was not affected by histamine H1 or H2 receptor antagonists. 5'-Guanylyl-diphosphoimide (Gpp(NH)p), but not GTP, stimulated both the basal and PGE1-stimulated adenylyl cyclase activities, although the percentage stimulation by maximal PGE was the same with or without Gpp(NH)p. NaF stimulation was also additive to that of PGE1. Secretin also stimulated gastric mucosal adenylyl cyclase activity (Kalpha congruent to 30 nM). Maximal secretin activation was not additive to that of PGE1, suggesting a coupling to the same adenylyl cyclase catalytic site. These studies suggest that mucosal membranes may contain beta-adrenergic receptors. The adenylyl cyclase activating agents used in this study, PGE1, secretin, and the catecholamines, are all known inhibitors of gastric acid secretion, suggesting a possible involvement of cyclic AMP in the inhibition of acid secretion in the rat stomach.