Postsynaptic alpha 2-adrenoceptors predominate over alpha 1-adrenoceptors in canine tracheal smooth muscle and mediate neuronal and hormonal alpha-adrenergic contraction.
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 fmoles/mg of protein; n = 5) in tracheal smooth muscle membranes, whereas [3H]prazosin revealed a low density of alpha 1-receptors (11.1 +/- 2.9 fmoles/mg of protein; n = 5). In peripheral lung membranes, however, alpha 1-receptors predominated (46.8 +/- 7.7 fmoles/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 microM prazosin (16%), potently inhibited by 0.3 microM yohimbine (89%), and abolished by a combination of the two drugs. The response to neuronally released norepinephrine is therefore mediated predominantly by alpha 2-receptors. The rank order of potency for adrenergic agonists was clonidine greater than norepinephrine greater than 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 microM prazosin but markedly inhibited by 0.3 microM 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).
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D007700:Kinetics; D008168:Lung / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011224:Prazosin / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011224:Prazosin