RECEPTOR INTERACTIONS OF IMIDAZOLINES: α‐ADRENOCEPTORS OF RAT AND RABBIT AORTAE DIFFERENTIATED BY RELATIVE POTENCIES, AFFINITIES AND EFFICACIES OF IMIDAZOLINE AGONISTS

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Abstract
1 Noradrenaline and a series of imidazolines were used to characterize and differentiate the postsynaptic α-adrenoceptors of rat and rabbit aortae. 2 Dose-response curves in each tissue revealed marked differences in the profile of agonist activity among the compounds. Based on the ED50 values for each compound, a rank order of potency of oxymetazoline > noradrenaline > tramazoline > tetrahydrozoline > clonidine was obtained in rabbit aorta and an order of noradrenaline > clonidine > tramazoline > oxymetazoline was obtained in rat aorta. Tetrahydrozoline had no agonist activity in rat aorta. 3 Dissociation constants were determined for each agonist in rat and rabbit aortae. Again, differences between the tissues were observed to the extent that the rank order of affinities for the imidazolines were exactly opposite for the two tissues. In rabbit aorta the order was, oxymetazoline > tramazoline > tetrahydrozoline > clonidine, whereas in rat aorta it was, clonidine > tetrahydrozoline > tramazoline > oxymetazoline. The extremes in tissue selectivity were observed with clonidine, which had approximately 125 fold higher affinity in rat aorta, and oxymetazoline, which had approximately 4 times higher affinity in rabbit aorta. 4 The absolute values of relative efficacies of the imidazolines studied, and their rank order, also differed between the two tissues. The relative efficacies of oxymetazoline and tramazoline were more than 15 fold greater in rabbit aorta than in rat aorta. Furthermore, tetrahydrozoline had a greater relative efficacy than clonidine in rabbit aorta while the converse was true in rat aorta. 5 Differences in the rank order of potency, affinity and relative efficacy of noradrenaline and a series of imidazolines in rat and rabbit aortae indicate that the postsynaptic α-adrenoceptors in these tissues are different. While the postsynaptic α-adrenoceptor of rabbit aorta is clearly of the α1-subtype, the exact nature of the postsynaptic α-receptor of rat aorta is not clear. The unique α-receptor of rat aorta has properties of both α1- and α2-adrenoceptors.