title: Study of the mechanisms involved in the bradykinin-induced contraction of the pig iris sphincter muscle in vitro.
abstract: This study was designed to investigate the mechanisms by which bradykinin induces contraction of the pig iris sphincter muscle in vitro. Addition of bradykinin, Lys-bradykinin and Met-Lys-bradykinin to the pig iris sphincter resulted in a graded contraction with a mean EC(50s) of 21, 11 and 5 nM, respectively. The bradykinin B(1) receptor agonist des-Arg(9)-bradykinin only caused a slight contraction, measured 6 h after the tissue was set up. The B(2) receptor antagonists FR 173657 ((E)-3-(6-acetamido-3-pyridyl)-N [N-2-4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]-N-methylamino-carbonyl-ethyl] acrylamide) and Hoe 140 (D-Arg(0)-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin produced a graded shift to the right associated with marked inhibition of the bradykinin-induced contraction. Atropine, guanethidine or tetrodotoxin significantly reduced the bradykinin-induced contraction. Dazoxiben, an inhibitor of thromboxane A(2), and MK-571 (3-(3-(2-(7-chloro-2-quinolinyl) ethenyl) phenyl ((3-dimethyl amino-3oxo-propyl) thio) methyl) propanoic acid, a leukotriene D(4) receptor-selective antagonist, also caused inhibition of the bradykinin-mediated contraction. Cyclooxygenase-1 and -2 inhibitors, indomethacin, ibuprofen, valeryl salicylate and NS 398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]methanosulfonamide) all significantly inhibited the bradykinin-mediated contraction without affecting the carbachol-induced contraction of the pig iris sphincter. Taken together, these results indicate that the bradykinin-mediated contraction of the pig iris sphincter muscle seems to be mediated primarily by the activation of the B(2) receptor release of acetylcholine, noradrenaline and both cyclooxygenase-1 and -2 metabolites besides the release of leukotriene D(4) and tromboxane A(2) from the arachidonic acid pathway.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, SC, 88015-420, Florianópolis, Brazil.
authors.forename: Mariem
authors.initials: M
authors.lastname: El Sayah
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007498:Iris / Q000187:drug effects* / Q000502:physiology; D007609:Kallidin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009578:Nitrobenzenes / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; C105311:FR 173657; D007093:Imidazoles; D009578:Nitrobenzenes; D011422:Propionates; D011804:Quinolines; D012459:Salicylates; D013449:Sulfonamides; C401835:valerylsalicylate; C029166:dazoxiben; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; D013779:Tetrodotoxin; C018103:bradykinin, Met-Lys-; C059141:verlukast; D001285:Atropine; C065679:icatibant; D013930:Thromboxane-A Synthase; D001920:Bradykinin; D007052:Ibuprofen; D007213:Indomethacin; D006145:Guanethidine