BETA-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 Rb-86+ efflux have been made in bovine isolated trachealis with the objectives of (a) identifying which of the P-adrenoceptor subtypes mediates the opening of plasmalemmal K+-channels, (b) gaining further insight into the properties of the novel, long-acting beta2-adrenoceptor agonist, salmeterol and (c) clarifying the role of K+-channel opening in mediating the mechano-inhibitory actions of agonists at beta-adrenoceptors. 2 In bovine trachealis muscle strips precontracted with histamine (460 muM), isoprenaline (0.1 nM-1 muM), procaterol (0.1-10 nm) and salmeterol (0.1-10 nm) each caused concentration-dependent relaxation. 3 ICI 118551 (10 nm-1 muM) 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 muM) failed to antagonize isoprenaline, procaterol or salmeterol. 4 Salmeterol (1 - 10 muM) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (I muM). 5 Cromakalim (10 muM), isoprenaline (100 nm-10 muM), procaterol (10 nm-1 muM) and salbutamol (100 nm- 10 muM) each promoted the efflux of Rb-86+ from strips of bovine trachealis muscle preloaded with the radiotracer. In contrast, salmeterol (100 nm-10 muM) failed to promote Rb-86+ efflux. 6 CGP 201712A (1 muM), ICI 118551 (100 nm) and salmeterol (I muM) did not themselves modify Rb-86+ efflux from trachealis muscle strips, nor did they affect the promotion of Rb-86+ efflux induced by cromakalim (10 muM). In contrast, CGP 20712A (I muM) and ICI 118551 (100 nm) were each able to inhibit the promotion of Rb-86+ efflux induced by isoprenaline (I muM) or procaterol (100 nm). Furthermore, salmeterol (10 muM) inhibited isoprenaline (I muM)-induced promotion of Rb-86+ efflux. 7 It is concluded that, in bovine trachealis, activation of either beta1- or beta2-adrenoceptors can promote the opening of Rb-86+-permeable K+-channels in the plasmalemma. The failure of salmeterol to promote plasmalemmal K+-channel opening may reflect, not its selectivity in activating beta2- as opposed to beta1-adrenoceptors, but rather its low intrinsic efficacy at beta2-adrenoceptors. The opening of plasmalemmal K+-channels plays a supportive rather than a crucial role in mediating the mechano-inhibitory effects of agonists at beta-adrenoceptors acting on trachealis muscle.