[Pharmacological evidence for the existence of beta 3-adrenergic receptors in canine airway smooth muscle].

There is increasing evidence for the existence of a third atypical beta-adrenergic receptor (beta 3-adrenoceptor) in various tissues including adipocytes, cardiac myocytes and intestinal smooth muscle preparations. In the present study, to determine whether beta 3-adrenoceptors also exist in the airway smooth muscle, we studied isolated bronchial segments from dogs under isometric conditions in vitro. Application of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 10(-5) M acetylcholine, the order of potency being isoproterenol (1) > or = salbutamol, a beta 2-selective adrenoceptor agonist (0.95) > or = BRL 37344, a beta 3-selective adrenoceptor agonist, (0.83) >> norepinephrine (0.10). Under the condition in which alpha- and beta 1-adrenoceptors had been blocked by phentolamine and ICI 89406, respectively, the relaxant response to salbutamol was competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551, and the pA2 value was 7.01 +/- 0.25 (mean +/- SE), whereas the response to BRL 37344 was resistant, with of apparent pA2 value of 5.66. However, cyanopindolol, an antagonist atypical beta-adrenoceptors, antagonized BRL 37344-induced relaxation in a competitive fashion with a pA2 of 6.74 +/- 0.11. This pA2 value was lower than that when salbutamol was used as an agonist (p < 0.05). These results indicate that beta 3-adrenoceptors probably exist in canine bronchial smooth muscle, and that stimulation of this type of receptors produces potent bronchodilation. Therefore, a specific agonist for beta 3-adrenoceptors could be valuable in the treatment of asthma.