Inhibition of human colonic adenylate cyclase by RMI 12330 A.

RMI 12330 A, a compound of the lactamamide series, is a potent inhibitor of vasoactive intestinal polypeptide(VIP)- and prostaglandin (PG)-stimulated colonic secretion in the rat. This substance was tested on the adenylate cyclase system in human colonic mucosa. RMI 12330 A inhibited PGE2-, 16,16-dimethyl-PGE2- as well as VIP-sensitive adenylate cyclases in a dose-related manner. Half-maximal inhibition of hormone-stimulated enzyme activities occurred at a lactamimide concentration of about 0.15 mM. Lactamimide inhibition was non-competitive. Our results are compatible with the concept of RMI 12330 A acting as an inhibitor of colonic secretion via inhibition of hormone-sensitive adenylate cyclase. Since basal, NaF- and guanylyl-imidodiphosphate-stimulated enzyme activities were also affected by this compound, we may conclude that RMI 12330 A is a non-specific inhibitor of the human colonic adenylate cyclase system.