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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 α 1 ‐and α 2 ‐adrenoceptors
Author(s) -
Daly C.J.,
McGrath J.C.,
Wilson V.G.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11669.x
Subject(s) - adrenergic , chemistry , adrenergic receptor , vein , muscle contraction , endocrinology , medicine , receptor
1 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 α 1 ‐ or α 2 ‐adrenoceptors. 2 The rank order of potency of various agonists is consistent with a population of α 2 ‐adrenoceptors; UK‐14304 > (—)‐noradrenaline = (—)‐adrenaline > B‐HT 920 = cirazoline > phenylephrine > amidephrine, but the rank order of pA 2 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 α 1 ‐ and α 2 ‐adrenoceptors or, alternatively, a new subtype with characteristics of both the α 1 ‐ and α 2 ‐subtypes. 3 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 α 2 ‐adrenoceptor antagonists rauwolscine and CH‐38083: these responses were inhibited by the selective α 1 ‐adrenoceptor antagonists prazosin and YM‐12617, but not by the selective α 2 ‐adrenoceptor antagonist BDF‐6143 and, (c) the relative potency of the yohimbine diastereoisomers rauwolscine and corynanthine against NA, phenylephrine and UK‐14304. 4 In spite of the overwhelming evidence for a population of postjunctional α 2 ‐adrenoceptors, prazosin was similarly effective against all agonists and failed to discriminate between those with putative selectivity for α 1 ‐ and α 2 ‐adrenoceptors. This suggests an interaction of the effects of agonists at the two α‐adrenoceptor subtypes. 5 An attempt has been made to reconcile a number of paradoxical observations with regard to the identification of postjunctional α 2 ‐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.