Abstract

Adrenoceptors mediating relaxant responses to exogenously added or endogenously released catecholamines in isolated canine bronchi (3rd-6th order) were characterized using selective beta receptor agonists and antagonists. Norepinephrine (3 x 10(7) to 3 x 10(-5) M) or isoproterenol (3 x 10(-8) to 10(-6) M) fully relaxed tissues precontracted with 3 x 10(-7) M carbachol (Cch). Salbutamol (Sal) also relaxed Cch-precontracted tissues, but this relaxant effect was extremely sensitive to the concentration of precontracting agent used: the maximal effect of Sal was 100, 79 and 28% reversal of tone in tissues precontracted with 2 x 10(-8), 10(-7) and 3 x 10(-7) M Cch. The effects of isoproterenol were antagonized by propranolol. Norepinephrine relaxations were antagonized by the beta-1-selective antagonist ICI 89,406 (pA2 = 7.70) and the beta-2-selective antagonist ICI 118,551 (pA2 = 6.33). Sal-relaxations were antagonized by ICI 118,551 (pA2 = 8.91). Field stimulation in tissues precontracted with McNeil A343 (M1-selective muscarinic agonist) produced transient relaxations which were antagonized by ICI 89,406 but not ICI 118,551 (both 10(-9) to 10(-7) M). Thus, exogenous and endogenous catecholamines relax canine bronchial smooth muscle by activating both beta-1 and beta-2 adrenoceptors, although the latter seen to play a significant role only when low concentrations of Cch were used.