Beta 2- but not beta 1-adrenoceptors mediate the adrenergic component of reflex tracheal dilatation during bronchoconstriction in guinea pigs in vivo.
Involvement of beta 1- and/or beta 2-adrenoceptors in vagal reflex-mediated tracheal dilatation during bronchoconstriction was investigated using the in vivo guinea pig tracheo-bronchi separated preparation. Inhalation of 0.01% (w/v) histamine to the bronchial site produced vagal reflex-mediated tracheal constriction followed by dilatation slightly after bronchial constriction. The latter reflex dilatation was significantly inhibited not only by 1% propranolol, a nonselective beta-adrenoceptor antagonist, but also by 0.1% butoxamine and 0.01% ICI-118,551, selective beta 2-adrenoceptor antagonists. However, 0.1% atenolol, a selective beta 1-adrenoceptor antagonist failed to inhibit the dilatation. Furthermore, the dilatation was also inhibited by 0.1% guanethidine treatment or adrenalectomy. All of noradrenaline, adrenaline and cyclic AMP contents in the tissue of the tracheal site significantly increased during the reflex tracheal dilatation after bronchoconstriction. The increase in cyclic AMP was reduced by 1% propranolol. Furthermore, local treatment of the tracheal site with 0.01% noradrenaline or 0.01% adrenaline induced tracheal dilatation, which was significantly inhibited by 0.1% butoxamine or 0.001% ICI-118,551 but not by 0.1% atenolol. These results suggest that the reflex tracheal dilatation during bronchoconstriction may be mediated by mainly beta 2-adrenoceptors activated by adrenaline released from the adrenal medulla and by noradrenaline released from the adrenergic nerve terminals.
Department of Pharmacology, SS Pharmaceutical Co., Ltd., Chiba, Japan.
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Y
Takahashi
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H
Ohno
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Misawa
D000280:Administration, Inhalation; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D014630:Vagus Nerve / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D006632:Histamine; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine