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

Abstract

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. 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. 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. Salmeterol (1–10 μm) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (1 μm). 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. 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. 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. 1993 British Pharmacological Society