Activation of Rat Gastric Mucosal Adenylyl Cyclase by Secretory Inhibitors

Prostaglandin (PG) E 1 , E 2 , A 1 , and A 2 stimulated rat gastric corpus mucosal membrane adenylyl cyclase activity. PGE 1 ( K a ≃ 8 μm) affected the maximum velocity but not the affinity of the enzyme for ATP and maximum PGE, activation was not affected by histamine H 1 or H 2 receptor antagonists. 5′-Guanylyl-diphosphoimide (Gpp(NH)p), but not GTP, stimulated both the basal and PGE 1 -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 PGE,. Secretin also stimulated gastric mucosal adenylyl cyclase activity ( K a ≃30 nm). Maximal secretin activation was not additive to that of PGE 1 , suggesting a coupling to the same adenylyl cyclase catalytic site. These studies suggest that mucosal membranes may contain β-adrenergic receptors. The adenylyl cyclase activating agents used in this study, PGE 1 , 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.