Adrenaline produces the relaxation of guinea-pig airway smooth muscle primarily through the mediation of beta(2)-adrenoceptors.
The beta-adrenoceptor subtype that mediates adrenaline-induced relaxation was pharmacologically identified in smooth muscle cells of the isolated guinea-pig trachea. Adrenaline produced a concentration-dependent relaxation with a pD(2) value of 7.1. The concentration-response curve for adrenaline was shifted rightwards in a competitive fashion by the beta(1)-/beta(2)-nonselective antagonists propranolol and bupranolol, with pA(2) values of 8.85 and 8.97, respectively. Adrenaline-induced relaxation was not affected by the beta(1)-selective antagonists atenolol and CGP-20, 712A within the concentration ranges supposed to antagonize the beta(1)-subtype (atenolol, <or=10(-6) M; CGP-20, 712A, <or=10(-8) M). By contrast, the concentration-response curve for adrenaline was shifted rightwards in a competitive fashion by atenolol at concentrations >or=3x10(-6) M with a pA(2) value of 5.77. The concentration-response curve for adrenaline was also competitively antagonized by the beta(2)-selective antagonists butoxamine and ICI-118,551 with pA(2) values of 6.86 and 8.73, respectively. The pA(2) values of beta-adrenoceptor antagonists (propranolol, bupranolol, atenolol, butoxamine and ICI-118,551) tested against adrenaline were consistent with the values when tested against salbutamol, a beta(2)-selective adrenoceptor agonist. The present findings provide evidence that the relaxant response of the smooth muscle of the guinea-pig trachea to the adrenal medulla hormone, adrenaline, is mainly mediated through beta(2)-adrenoceptors.
Tanaka
Yoshio
Y
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Science, Miyama 2-2-1, Funabashi-city, Chiba 274-8510, Japan. yotanaka@phar.toho-u.ac.jp
Yamashita
Yoko
Y
Horinouchi
Takahiro
T
Koike
Katsuo
K
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects*; D009994:Osmolar Concentration; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol; D004837:Epinephrine