BETA(3)-ADRENOCEPTOR AGONISTS, BRL-37344 AND SR-58611A, DO NOT INDUCERELAXATION OF HUMAN, SHEEP AND GUINEA-PIG AIRWAY SMOOTH-MUSCLE IN-VITRO

The existence of atypical- or beta(3)-adrenoceptors has now been gener ally accepted. These receptors have been shown to be abundant in adipo se tissue and in a number of gastrointestinal smooth muscle preparatio ns. A recent study reported that beta(3)-adrenoceptor stimulation medi ated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species. We investigated the in vitro responses of guinea-pig, human and sheep br onchial smooth muscle to isoprenaline, salbutamol (a selective beta(2) -adrenoceptor agonist), and BRL 37344 and SR 58611A (two presumably se lective beta(3)-adrenoceptor agonists). The preparations were precontr acted to 60-70% of maximal tension with histamine 10(-6) M for guinea- pig and human bronchi, or acetylcholine 10(-6) M for sheep bronchi. In each species, SR 58611A produced a slight fall in tension of about 10 % of the effects of theophylline (3 mM), but this decrease in tension was not significantly different from the spontaneous and weak relaxati on observed with saline addition during the same duration of the exper iment. These relaxations were not modified by either the nonselective beta-adrenoceptor antagonist propranolol or the selective beta(2)-adre noceptor antagonist ICI 118,551. In contrast, BRL 37344 induced a sign ificant concentration-dependent fall in tension induced by both spasmo gens. Its relaxant effects were inhibited both by propranolol and ICI 118,551 in human and guinea-pig airways, whereas on the isolated sheep bronchus BRL 37344-induced relaxations were only slightly, albeit sig nificantly, reduced with either of the beta-adrenoceptor antagonists t ested. Salbutamol and isoprenaline induced potent relaxations of guine a-pig, human and sheep airway smooth muscle in vitro, which were antag onized both by propranolol and ICI 118,551. Our findings show that bet a(3)-adrenoceptor stimulation does not induce relaxation in guinea-pig , human and sheep bronchial smooth muscle, and that a beta(2)-adrenoce ptor agonistic component might be implicated in the relaxant effects o f BRL 37344.