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 'Rb+ 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 P2-adrenoceptor agonist, salmeterol and (c) clarifying the role of K+-channel opening in mediating the mechanoinhibitory actions of agonists at P-adrenoceptors.2 In bovine trachealis muscle strips precontracted with histamine (460 1M), isoprenaline (0.1 nM-1 pM), procaterol (0.1-10 nM) and salmeterol (0.1-10 nM) each caused concentration-dependent relaxation. 3 ICI 118551 (10 nM-I1 M) antagonized isoprenaline, procaterol and salmeterol in suppressing histamine-induced tone of the isolated trachealis muscle. The antagonism was concentration-dependent. In contrast, CGP 20712A (1O nM-1AM) failed to antagonize isoprenaline, procaterol or salmeterol.4 Salmeterol (1-10 ;LM) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (1 gM).5 Cromakalim (10 1AM), isoprenaline (100 nM-10 AM), procaterol (10 nM-1 1AM) and salbutamol (100 nM-10-1M) each promoted the efflux of 86Rb+ from strips of bovine trachealis muscle preloaded with the radiotracer. In contrast, salmeterol (100 nM-1O 1M) failed to promote 86Rb+ efflux. 6 CGP 201712A (1 1AM), ICI 118551 (100 nM) and salmeterol (1 1AM) did not themselves modify 86Rb+ efflux from trachealis muscle strips, nor did they affect the promotion of 86Rb+ efflux induced by cromakalim (10 1M). In contrast, CGP 20712A (1I1M) and ICI 118551 (100nM) were each able to inhibit the promotion of 86Rb+ efflux induced by isoprenaline (1 1aM) or procaterol (100 nM). Furthermore, salmeterol (10I1AM) inhibited isoprenaline (1 1AM)-induced promotion of 86Rb+ efflux.7 It is concluded that, in bovine trachealis, activation of either 13l-or P2-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 P2-as opposed to V-adrenoceptors, but rather its low intrinsic efficacy at P2-adrenoceptors. The opening of plasmalemmal K+-channels plays a supportive rather than a crucial role in mediating the mechano-inhibitory effects of agonists at P-adrenoceptors acting on trachealis muscle. Keywords: Trachealis muscle; 86Rb+ efflux; P-adrenoceptor subtypes; K+-channels; isoprenaline; procaterol; salbutamol; salmeterol; CGP 20712A; ICI 118551 IntroducdonAs background to the experiments described in the preceding paper (Cook et al., 1993) we reviewed the substantial evidence that suggests that agonists at P-adrenoceptors relax airways smooth muscle by mechanisms associated with the opening of plasmalemmal K+-channels. That such K+-channel opening is mediated by the activation of P-adrenoceptors is indicated by the ability of propranolol to inhibit the hyperpolarization of airways smooth muscle induced by isoprenaline (Ito & Tajima, 1...

β‐Adrenoceptor subtypes and the opening of plasmalemmal K+‐channels in trachealis muscle: electrophysiological and mechanical studies in guinea‐pig tissue

“…We thus conclude that the activation of either ,or P2-adrenoceptors can promote K+-channel opening in trachealis muscle. This conclusion receives strong support from the results of our studies of 86Rb+ efflux from bovine trachealis (Chiu et al, 1993).…”

“…Other objectives of the present experiments were to shed more light on the role of K+-channel opening in mediating the mechano-inhibitory effects of the agonists at B-adrenoceptors and to characterize further the pharmacological properties of the novel, longacting P2-adrenoceptor agonist, salmeterol (Ball et al, 1991;Dougall et al, 1991). The present electrophysiological and mechanical studies of guinea-pig trachealis were carried out in parallel with studies of mechanical activity and 86Rb+ efflux in bovine trachealis (Chiu et al, 1993). Some of our findings have been the subject of communications to the British Pharmacological Society Tissue bath studies with isolated trachea Small segments of trachea were set up for the isometric recording of tension changes essentially as described by Foster et al (1983).…”

β-Adrenoceptor stimulation activates large-conductance Ca2+-activated K+ channels in smooth muscle cells from basilar artery of guinea pig

“…As noted in the Introduction, this effect would deactivate voltage-dependent Ca 2 § channels, thus decreasing steady-state Ca 2 § influx and so favor vasorelaxation. An important role for the BK channel in mediating smooth muscle relaxation has been identified in trachealis muscle [9,10,14] and the data presented here indicate that this channel could serve a comparable role in cerebrovascular smooth muscle. Our observations do not, however, address the crucial question of whether activation of the BK channel is required for vasorelaxation or whether, as recently argued for trachealis muscle [9,10], activation of this channel plays merely a supportive role.…”

The involvement of ATP‐sensitive potassium channels in β‐adrenoceptor‐mediated vasorelaxation in the rat isolated mesenteric arterial bed

“…Furthermore, a recent study on the rat basilar artery in vivo has demonstrated that noradrenaline acts via fI-adrenoceptors to cause glibenclamide-sensitive vasodilatation (Kitazono et al, 1993). The coupling of f-adrenoceptors to potassium currents has also been reported in non-vascular tissues including pulmonary smooth muscle, where the responses are linked to calcium-activated potassium channels Chiu et al, 1993), and cardiac tissue, where the receptors are coupled to KATP-channels (Schackow & Ten Eick, 1994). Evidence is therefore accumulating to indicate the involvement of KATPchannels in P-adrenoceptor-mediated responses.…”

“…physiological evidence has demonstrated that isoprenaline causes hyperpolarization of the canine saphenous vein which is sensitive to glibenclamide (Nakashima & Vanhoutte, 1995). Furthermore, studies on both guinea-pig and bovine isolated trachealis muscle indicate that f-adrenoceptor agonists may activate potassium channels leading to hyperpolarization, which contributes towards the relaxant effects of these agents Chiu et al, 1993). Such a hyperpolarizing action of isoprenaline, via potassium channels, has previously been identified in rat myometrial muscle (Kroeger & Marshall, 1973).…”