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

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 β2-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 salmeterol (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) failed to promote 86Rb+ efflux. 6 CGP 201712A (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 β1- or β2-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 β2- as opposed to β1-adrenoceptors, but rather its low intrinsic efficacy at β2-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.