β-Adrenoceptor subtypes and the opening of plasmalemmal K +-channels in bovine trachealis muscle: Studies of mechanical activity and ion fluxes

Abstract

1. Studies of mechanical activity and 86Rb + efflux have been made in bovine isolated trachealis with the objectives of (a) identifying which of the β-adrenoceptor subtypes mediates the opening of plasmalemmal K +-channels, (b) gaining further insight into the properties of the novel, long-acting β 2-adrenoceptor agonist, salmeterol and (c) clarifying the role of K +-channel opening in mediating the mechano-inhibitory actions of agonists at β-adrenoceptors. 2. In bovine trachealis muscle strips precontracted with histamine (460 μM), isoprenaline (0.1 nM-1 μM), procaterol (0.1-10 nm) and samleterol (0.1-10 nM) each caused concentration-dependent relaxation. 3. ICI 118551 (10 nM-1 μM) antagonized isoprenaline, procaterol and salmeterol in suppressing histamine-induced tone of the isolated trachealis muscle. The antagonism was concentration-dependent. In contrast, CGP 20712A (10 nM-1 μM) failed to antagonize isoprenaline, procaterol or salmeterol. 4. Salmeterol (1-10 μM) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (1 μM). 5. Cromakalim (10 μM), isoprenaline (100 nM-10 μM), procaterol (10 nM-1 μM) and salbutamol (100 nM-10 μM) each promoted the efflux of 86Rb + from strips of bovine trachealis muscle preloaded with the radiotracer. In contrast, salmeterol (100 nM-10 μM) filed to promote 86Rb + efflux. 6. CGP 20712A (1 μM), ICI 118551 (100 nM) and salmeterol (1 μM) did not themselves modify 86Rb + efflux from trachealis muscle strips, nor did they affect the promotion of 86Rb + efflux induced by cromakalim (10 μM). In contrast, CGP 20712A (1 μM) and ICI 118551 (100 nM) were each able to inhibit the promotion of 86Rb + efflux induced by isoprenaline (1 μM) or procaterol (100 nM). Furthermore, salmeterol (10 μM) inhibited isoprenaline (1 μM)-induced promotion of 86Rb + efflux. 7. It is concluded that, in bovine trachealis, activation of either β 1- or β 2-adrenoceptors can promote the opening of 86Rb +-permeable K +-channels in the plasmalemma. The failure of salmeterol to promote plasmalemmal K +-channel opening may reflect, not its selectivity in activating β 2- as opposed to β 1-adrenoceptors, but rather its low intrinsic efficacy at β 2-adrenoceptors. The opening of plasmalemmal K +-channels plays a supportive rather than a crucial role in mediating the mechano-inhibitory effects of agonists at β-adrenoceptors acting on trachealis muscle.