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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003106:Colon / Q000201:enzymology*; D003517:Cyclopentanes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004794:Enzyme Repression; D006801:Humans; D007097:Imines / Q000008:administration & dosage / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology; D007419:Intestinal Secretions / Q000201:enzymology; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology
D003517:Cyclopentanes; D007097:Imines; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases