EFFECTS OF 2 BETA(3)-ADRENOCEPTOR AGONISTS, SR-58611A AND BRL-37344, AND OF SALBUTAMOL ON CHOLINERGIC AND NANC NEURAL CONTRACTION IN GUINEA-PIG MAIN BRONCHI IN-VITRO

1 The aim of the present study was to investigate the type of adrenoce ptor which modulates constriction of the guinea-pig isolated main bron chus in response to electrical field stimulation (EFS). Drugs used wer e salbutamol and two agonists reportedly selective for the putative be ta3-adrenoceptor: BRL 37344 and SR 58611A. 2 At basal tone, all three drugs induced relaxation, however, SR 58611A and BRL 37344 (10(-9) to 10(-6) M) relaxed guinea-pig isolated main bronchus more weakly than s albutamol (10(-9) to 10(-6) m). The effects observed at 10(-6) m were 43% +/- 9%, 63% +/- 4% and 98% +/- 1% of the maximal effect induced by theophylline (3 x 10(-3) M) for SR 58611A, BRL 37344 and salbutamol, respectively.3 SR 58611A and BRL 37344 (10(-8) to 10(-6) m) did not si gnificantly modify the cholinergic component of the response to EFS, b ut caused a concentration-dependent reduction of the nonadrenergic non cholinergic (NANC) excitatory component (41.8% +/- 10.1% and 56.8% +/- 7.4% respectively at 10(-6) M, n = 6-7). Salbutamol (10(-9) to 10(-7) M) strongly inhibited both components, with 91.1% +/- 4.2% of inhibit ion for the NANC contraction and 62.0% +/- 5.2% of inhibition for the cholinergic contraction (10(-7) M, n = 7). 4 Whereas the inhibitory ef fects of salbutamol were strongly inhibited by both propranolol (10(-6 ) M) and ICI 118,551 (10(-6) M), those of BRL 37344 were only slightly , albeit significantly reduced by both propranolol and ICI 118,551, an d those of SR 58611A were unaffected by treatment with either beta-adr enoceptor antagonist. An alpha2-adrenoceptor antagonist, yohimbine, di d not influence the inhibitory effects of any of the beta-adrenoceptor agonists tested. 5 Concentration-response curves to acetylcholine (10 (-8) to 10(-3) M), [Nle10]NKA(4-10) (10(-10) to 10(-6) M) and substanc e P (10(-10) to 3 x 10(-6) M) were also significantly shifted to the r ight by salbutamol (10(-6) M), whereas SR 5861 IA and BRL 37344 (10(-6 ) m) had no effect. 6 These results suggest that the stimulation of pu tative beta3-adrenoceptors exerts a specific prejunctional inhibitory action on NANC excitatory response induced by EFS of the isolated main bronchus of the guinea-pig. They also suggest that a beta2-adrenocept or agonistic component may be involved in the effects of BRL 37344.