Comparison of potency of α2‐adrenoceptor antagonists in vitro: evidence for heterogeneity of α2‐adrenoceptors

Abstract

1 A comparison has been made of affinity of α‐adrenoceptor antagonists for α₂ binding sites in radioligand binding assays, and functional antagonist activity at pre‐ and postjunctional α₂‐adrenoceptors in various in vitro preparations. 2 The antagonists displaced [³H]‐rauwolscine from rat brain and rabbit spleen membranes but there were substantial differences in rank order and absolute potency in the two tissues. 3 pA₂ values for yohimbine, phentolamine and Wy26703 against the selective α₂ agonist UK‐14,304 were determined in the rat left atrium, rat and rabbit vas deferens and rabbit saphenous vein preparations. The pA₂ values varied substantially between the tissues, differing by two orders of magnitude in the case of Wy26703. Yohimbine was more potent in rabbit preparations while Wy26703 was markedly more potent in all the rat preparations. 4 Yohimbine and Wy26703 were compared in the dog saphenous vein preparation where pre‐ and postjunctional α₂ antagonist activity can be compared in the same tissue. As in the rabbit preparations, yohimbine was more potent than Wy26703 at both sites but the absolute potencies were different. 5 It is concluded that α₂‐adrenoceptors are a heterogeneous population, different subgroups being more apparent between species rather than between tissue types or location.