Differential interactions of clonidine and methoxamine with the postsynaptic alpha-adrenoceptor of rabbit main pulmonary artery.
We investigated the dependence upon extracellular Ca2+ of contractile responses of the isolated rabbit main pulmonary artery to the alpha-adrenoceptor subtype-selective agonists clonidine (alpha 2) and methoxamine (alpha 1). The calcium-entry blocker verapamil caused a weak, surmountable antagonism of contractile responses to methoxamine, whereas the concentration-response curve of clonidine was antagonized in a noncompetitive manner with a marked depression of maximal responses. Withdrawal of Ca2+ from the physiological saline solution virtually abolished contractile responses to clonidine, without significantly affecting methoxamine-induced responses. We, therefore, determined if clonidine and methoxamine were interacting with the same population of vascular postsynaptic alpha-adrenoceptors. We found that the alpha 1-antagonist prazosin and the alpha 2-antagonist yohimbine caused competitive blockade of contractile responses to both agonists. However, the potency of both antagonists was significantly greater against clonidine than methoxamine. This may reflect a heterogeneity in the population of postsynaptic alpha-adrenoceptors of the rabbit main pulmonary artery. On the other hand, the difference in extracellular Ca2+ sensitivity of clonidine- and methoxamine-induced contractions may be explained as a differential mode of stimulation of the postsynaptic alpha 1-adrenoceptor, possibly through separate, interacting recognition sites for both agonists.
D000818:Animals; D002118:Calcium / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D014700:Verapamil; D008729:Methoxamine; D003000:Clonidine; D002118:Calcium; D011224:Prazosin