ATYPICAL BETA-ADRENOCEPTOR (BETA-3-ADRENOCEPTOR) MEDIATED RELAXATION OF CANINE ISOLATED BRONCHIAL SMOOTH-MUSCLE

To determine whether atypical beta-adrenoceptors (beta3-adrenoceptors) exist in the airway smooth muscle, we studied isolated bronchial segments from dogs under isometric conditions in vitro. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 10(-5) M acetylcholine, rank-order potency being isoproterenol (1) greater-than-or-equal-to salbutamol (0.95) greater-than-or-equal-to BRL 37344, a beta3-selective adrenoceptor agonist (0.83) > norepinephrine (0.10). Under the condition that alpha- and beta1-adrenoceptors had been blocked, the relaxant response to salbutamol was competitively antagonized by the beta2-adrenoceptor antagonist ICI 118551 and the pA2 was 7.01 +/- 0.25 (SE), whereas the response to BRL 37344 was resistant, with an apparent pA2 of 5.66. However, cyanopindolol, an antagonist for atypical beta-adrenoceptors, antagonized the BRL-induced relaxation in a competitive manner, with a pA2 of 6.74 +/- 0.11. This pA2 was lower than that when salbutamol was used as an agonist (P < 0.05). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were increased by BRL 37344 in a concentration-dependent fashion. These results suggest that beta3-adrenoceptors may exist in canine bronchial smooth muscle and that the stimulation of this type of receptor causes a bronchodilation through a cAMP-dependent pathway.