CHARACTERIZATION OF BETA-ADRENOCEPTOR SUBTYPES IN CANINE AIRWAY SMOOTH-MUSCLE BY RADIOLIGAND BINDING AND PHYSIOLOGICAL-RESPONSES

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (2) , 456-461
Abstract
.beta.-Adrenoceptor subtypes in canine tracheal smooth muscle were investigated by radioligand binding and by physiological responses to .beta.-agonists and sympathetic nerve stimulation in vitro. Specific binding of [3H]dihydroalprenolol to tracheal smooth muscle membranes was of high affinity (Kd = 1.0 .+-. 0.08 nM), as in peripheral lung membranes from the same animals, but the concentration of binding sites (95.6 .+-. 4.7 fmol/mg of protein) was much lower than in lung (532 .+-. 48 fmol/mg of protein). Binding was stereoselective and agonists competed with the rank order of potency isoproterenol > epinephrine > norepinephrine, signifying a preponderance of .beta.2 receptors. Using selective .beta.-antagonists, the ratio of .beta.1/.beta.2 receptors in tracheal smooth muscle membranes was 1:4. The relaxation response of tracheal smooth muscle strips to exogenous .beta.-agonists was mediated by .beta.2 receptors, with a very small contribution from .beta.1 receptors. The relaxation response to electrical field stimulation of sympathetic nerves was mediated predominantly by .beta.1 receptors. Most .beta.-receptors in dog tracheal smooth muscle are apparently of the .beta.2 subtype and mediate responses to circulating catecholamines, but there is a small concentration of .beta.1 receptors which mediate the response to neurally released norepinephrine.