Activation of alpha-adrenergic response in tracheal smooth muscle: a postreceptor mechanism.
We have investigated the activation of alpha-adrenergic contractile responses in dog tracheal smooth muscle. After cholinergic and beta-adrenergic blockade, neither electrical field stimulation nor alpha-adrenergic agonists caused contraction of trachealis strips in vitro, but after exposure to histamine or serotonin a striking contractile response was obtained. Similar activation of the contractile response to norepinephrine was seen in isolated tracheal segments in vivo after exposure to histamine and serotonin. This response was mediated predominantly by alpha 2-adrenoceptors, because the alpha 2-antagonist yohimbine was a potent inhibitor whereas the alpha 1-antagonist prazosin was a weak inhibitor of the response to both electrical stimulation and exogenous agonists. Using [3H]yohimbine to label alpha 2-receptors and [3H]prazosin to label alpha 1-receptors, we confirmed the preponderance of alpha 2-receptors in trachealis membranes but found no increase in either receptor number or affinity after incubating muscle strips with histamine. The magnitude of alpha-adrenergic contraction was significantly related to the magnitude of precontraction by histamine and serotonin both in vitro and in vivo but persisted after washout. Acetylcholine was much less potent in activating the alpha-adrenergic response. We conclude that activation of airway alpha-adrenergic responses involves a postreceptor mechanism not directly related to membrane depolarization, but involving some related process such as activation of calcium channels.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D004285:Dogs; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011224:Prazosin / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012701:Serotonin; D006632:Histamine; D011224:Prazosin