title: Beta-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 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). In contrast, CGP 20712A (1 microM) and ICI 118551 (100nM) were each able to inhibit the promotion of 86Rb+ efflux induced by isoprenaline (1 microM) or procaterol (100 nM). Furthermore,salmeterol (10 microM) inhibited isoprenaline (1 microM)-induced promotion of 86Rb+ efflux.7. It is concluded that, in bovine trachealis, activation of either beta l- or beta 2-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 beta 2- as opposed to beta 1-adrenoceptors, but rather its low intrinsic efficacy at beta 2-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.
authors.affiliation: Department of Physiological Sciences, University of Manchester.
authors.forename: P
authors.initials: P
authors.lastname: Chiu
authors.forename: S J
authors.initials: SJ
authors.lastname: Cook
authors.forename: R C
authors.initials: RC
authors.lastname: Small
authors.forename: J L
authors.initials: JL
authors.lastname: Berry
authors.forename: J R
authors.initials: JR
authors.lastname: Carpenter
authors.forename: S J
authors.initials: SJ
authors.lastname: Downing
authors.forename: R W
authors.initials: RW
authors.lastname: Foster
authors.forename: A J
authors.initials: AJ
authors.lastname: Miller
authors.forename: A M
authors.initials: AM
authors.lastname: Small
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D012414:Rubidium Radioisotopes; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D015221:Potassium Channels; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D012414:Rubidium Radioisotopes; D000628:Aminophylline; C026777:ICI 118551; D006632:Histamine; C049763:CGP 20712A; D012413:Rubidium