title: Inhibition of gonadotropin-stimulated adenylate cyclase by dansyl-arginyl-(4'-ethyl)piperidine amide (DAPA).
abstract: Protease inhibitors are known to suppress basal, fluoride-, and hormone-stimulated adenylate cyclase activities. The thrombin inhibitor, dansyl-arginyl-(4'-ethyl)piperidine amide (DAPA), also specifically inhibits the binding of gonadotropins to their receptors. Our studies were undertaken to find a concentration of DAPA that would specifically inhibit gonadotropin-stimulated adenylate cyclase without significantly altering basal, fluoride-, isoproterenol-, or prostaglandin E1-stimulated cyclase. Basal adenylate cyclase activity was not inhibited by DAPA in either human chorionic gonadotropin (hCG)- or follicle-stimulating hormone (FSH)-responsive rat ovarian plasma membranes. Human chorionic gonadotropin-stimulated cyclase was completely inhibited by DAPA at a concentration of 2.96 mM; the ID50 was 1.32 mM. Follicle-stimulating hormone-stimulated cyclase was completely inhibited by a DAPA concentration of 4.44 mM, and the ID50 was 1.75 mM. Dansyl-arginyl-(4'-ethyl)piperidine amide (2.96 mM) inhibited isoproterenol-, prostaglandin E1-, and fluoride-stimulated cyclase in hCG-responsive membranes by 11%, 28%, and 35%, respectively. Dansyl-arginyl-(4'-ethyl)piperidine amide (4.44 mM) inhibited fluoride- and prostaglandin-stimulated cyclase in FSH-responsive membranes by 10% and 11%, respectively. The data show that appropriate concentrations of DAPA can antagonize gonadotropin-stimulated adenylate cyclase while only minimally affecting fluoride- and other receptor-activated cyclase activities.
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D010053:Ovary / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D006063:Chorionic Gonadotropin; C010812:OM 205; D012969:Sodium Fluoride; D005640:Follicle Stimulating Hormone; D001120:Arginine; D000262:Adenylyl Cyclases; D000527:Alprostadil; D007545:Isoproterenol