title: Pharmacological characterization of the beta-adrenoceptor that mediates the relaxant response to noradrenaline in guinea-pig tracheal smooth muscle.
abstract: Pharmacological characteristics of beta-adrenoceptors (beta-ARs) mediating noradrenaline-induced relaxation were investigated in guinea-pig tracheal smooth muscle. The inhibitory effects of several types of beta-AR antagonists on noradrenaline-induced relaxation against histamine contraction were scrutinized with Schild plot analysis. The concentration-response curve for noradrenaline obtained in the absence of phentolamine and uptake inhibitors was competitively antagonized by all of the beta-AR antagonists used in this study (propranolol, bupranolol, atenolol, butoxamine and ICI-118,551). However, their pA2 values were markedly less than the expected values for beta1-AR and beta2-AR. On the other hand, pA2 values of ICI-118,551 (6.85) determined in the presence of phentolamine suggested a contribution of a beta1 -AR rather than beta2 -AR. In the presence of phentolamine and uptake inhibitors (desipramine and deoxycorticosterone), the Schild plot for atenolol was a better fit, with two distinct straight lines. The pA2 values of atenolol provided by the regression were: approximately 7.0, which corresponds to the expected beta1-AR value, and approximately 6.5, which was 3 times less than the expected value for beta1 -AR, and thus the possible presence of two classes of beta1 -AR (beta1(Low) and beta1(High)) was suggested. This view was also supported by Schild plot analysis for propranolol, which fit two straight lines each with a slope of 1.0. The present findings indicate that beta1 -ARs contributing to noradrenaline-elicited relaxation in guinea-pig tracheal smooth muscle exhibit diverse pharmacological characteristics and may be subdivided into at least two classes with distinct affinities for atenolol. Under physiological conditions, beta1(Low) rather than beta1(High) seems to play a more significant role in noradrenaline-regulated airway smooth muscle tone.
authors.affiliation: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi-City, Chiba, 274-8510, Japan. yotanaka@phar.toho-u.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Michikawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horinouchi
authors.forename: Katsuo
authors.initials: K
authors.lastname: Koike
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002046:Bupranolol / Q000494:pharmacology; D002078:Butoxamine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D002078:Butoxamine; D003900:Desoxycorticosterone; C026777:ICI 118551; D001262:Atenolol; D006632:Histamine; D002046:Bupranolol; D011433:Propranolol; C049763:CGP 20712A; D000420:Albuterol; D003891:Desipramine; D009638:Norepinephrine; D010646:Phentolamine