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 beta-adrenoceptor subtypes mediates the opening of plasmalemmal K(+)-channels, (b) gaining further insight into the properties of the novel, long-acting beta 2-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 microM), isoprenaline (0.1 nM-1 microM), procaterol (0.1-10 nM) and salmeterol (0.1-10 nM) each caused concentration-dependent relaxation. 3. ICI 118551 (10 nM-1 microM) 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 microM) failed to antagonize isoprenaline, procaterol or salmeterol. 4. Salmeterol (1-10 microM) antagonized isoprenaline in relaxing strips of bovine trachea which had been precontracted with carbachol (1 microM). 5. Cromakalim (10 microM), isoprenaline (100 nM-10 microM), procaterol (10 nM-1 microM) and salbutamol (100 nM-10 microM) each promoted the efflux of 86Rb+ from strips of bovine trachealis muscle preloaded with the radiotracer. In contrast, salmeterol (100 nM-10 microM) failed to promote 86Rb+ efflux. 6. CGP 201712A (1 microM), ICI 118551 (100 nM) and salmeterol (1 microM) did not themselves modify 86Rb+ efflux from trachealis muscle strips, nor did they affect the promotion of 86Rb+ efflux induced by cromakalim (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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