Pharmacological analysis of postjunctional α‐adrenoceptors mediating contractions to (−)‐noradrenaline in the rabbit isolated lateral saphenous vein can be explained by interacting responses to simultaneous activation of α1‐and α2‐adrenoceptors

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Abstract
The pharmacological characteristics of the α‐adrenoceptor population in the rabbit isolated saphenous vein has been examined with (–)‐noradrenaline (NA), as principal agonist, and a number of antagonists with selectivity for either α1‐ or α2‐adrenoceptors. The rank order of potency of various agonists is consistent with a population of α2‐adrenoceptors; UK‐14304 > (—)‐noradrenaline = (—)‐adrenaline > B‐HT 920 = cirazoline > phenylephrine > amidephrine, but the rank order of pA2 values for the antagonists against (—)− noradrenaline: BDF‐6143 > rauwolscine = prazosin > CH‐38083 = YM‐12617 > Wy‐26703 = phentolamine > corynanthine, is indicative of a mixed population of α1‐ and α2‐adrenoceptors or, alternatively, a new subtype with characteristics of both the α1‐ and α2‐subtypes. Further evidence for two discrete populations of α‐adrenoceptors is provided by, (a) the potent but non‐competitive effect of prazosin against (—)‐noradrenaline, (b) the presence of a component of the contractions elicited by NA and phenylephrine which is resistant to the selective α2‐adrenoceptor antagonists rauwolscine and CH‐38083: these responses were inhibited by the selective α1‐adrenoceptor antagonists prazosin and YM‐12617, but not by the selective α2‐adrenoceptor antagonist BDF‐6143 and, (c) the relative potency of the yohimbine diastereoisomers rauwolscine and corynanthine against NA, phenylephrine and UK‐14304. In spite of the overwhelming evidence for a population of postjunctional α2‐adrenoceptors, prazosin was similarly effective against all agonists and failed to discriminate between those with putative selectivity for α1‐ and α2‐adrenoceptors. This suggests an interaction of the effects of agonists at the two α‐adrenoceptor subtypes. An attempt has been made to reconcile a number of paradoxical observations with regard to the identification of postjunctional α2‐adrenoceptors in vitro, and it is suggested that in many of the isolated blood vessels presently available for examination both subtypes reside on the same smooth muscle cell. The pharmacological consequences of multiple subtypes of receptors mediating the same response is considered.