POSTSYNAPTIC ALPHA-2-ADRENOCEPTORS PREDOMINATE OVER ALPHA-1-ADRENOCEPTORS IN CANINE TRACHEAL SMOOTH-MUSCLE AND MEDIATE NEURONAL AND HORMONAL ALPHA-ADRENERGIC CONTRACTION

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Abstract
.alpha.-Adrenoceptor subtypes in canine tracheal smooth muscle were investigated by radioligand binding and by in vitro responses of muscle strips to electrical field stimulation and exogenous .alpha.-agonists. [3H]Yohimbine identified a high density of .alpha.2-receptors (51.4 .+-. 4.9 fmol/mg of protein; n [no.] = 5) in tracheal smooth muscle membranes, whereas [3H]prazosin revealed a low density of .alpha.1-receptors (11.1 .+-. 2.9 fmol/mg of protein; n = 5). In peripheral lung membranes, .alpha.1-receptors predominated (46.8 .+-. 7.7 fmol/mg of protein; n = 4) over .alpha.2-receptors (4.1 .+-. 1.5 fmoles/mg of protein; n = 4). After pretreatment with atropine and propranolol and precontraction with serotonin or histamine, the contractile response of tracheal smooth muscle to electrical field stimulation was partially inhibited by 0.3 .mu.M prazosin (16%), potently inhibited by 0.3 .mu.M yohimbine (89%) and abolished by a combination of the 2 drugs. The response to neuronally released norepinephrine is mediated predominantly by .alpha.2-receptors. The rank order of potency for adrenergic agonists were clonidine > norepinephrine > phenylephrine in both competition studies with [3H]yohimbine and in contraction studies, signifying a predominance of postsynaptic .alpha.2-receptors. The contractile responses to exogenous norepinephrine, clonidine and phenylephrine were only weakly inhibited by 0.3 .mu.M prazosin but markedly inhibited by 0.3 .mu.M yohimbine, with a Kb of 1.2 nM, which was similar to the Kd of [3H]yohimbine binding to airway smooth muscle membranes (2.7 nM).