title: The bradykinin B2 receptor antagonist WIN 64338 inhibits the effect of des-Arg9-bradykinin in endothelial cells.
abstract: WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino) methylene] amino]-3-(2-naphthalenyl) 1-oxopropyl]amino]-phenyl]- tributyl, chloride, monohydrochloride) is the first potent nonpeptide competitive bradykinin B2 receptor antagonist as shown in classical pharmacological preparations with no activity in the rabbit aorta stimulated by the bradykinin B1 receptor agonist des-Arg9-bradykinin. In primary cultured bovine aortic endothelial cells, both bradykinin and des-Arg9-bradykinin stimulate the production of intracellular cyclic GMP, an index for the production of nitric oxide. Surprisingly, WIN 64338 did not inhibit bradykinin but abolished the effect of des-Arg9-bradykinin suggesting that kinin receptor antagonists do not necessarily discriminate between kinin receptor subtypes in an identical way in different tissues and species.
authors.affiliation: Hoechst AG, Frankfurt am Main, Germany.
authors.forename: K J
authors.initials: KJ
authors.lastname: Wirth
authors.forename: B A
authors.initials: BA
authors.lastname: Schölkens
authors.forename: G
authors.initials: G
authors.lastname: Wiemer
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D065168:Bradykinin Receptor Antagonists; D009281:Naphthalenes; D009943:Organophosphorus Compounds; C087374:WIN 64338; C024626:bradykinin, des-Arg(9)-; D009569:Nitric Oxide; D006152:Cyclic GMP; D001920:Bradykinin