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An attempt at selective protection from phenoxybenzamine of postjunctional α‐adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein
Author(s) -
Daly C.J.,
Dunn W.R.,
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.tb11670.x
Subject(s) - rauwolscine , phenoxybenzamine , prazosin , population , medicine , antagonist , endocrinology , adrenergic receptor , chemistry , receptor , biology , pharmacology , environmental health
1 An attempt has been made, with the irreversible α‐adrenoceptor antagonist phenoxybenzamine, to find the conditions under which postjunctional α 1 ‐adrenoceptors in the rabbit isolated saphenous vein can be inactivated, such that postjunctional α 2 ‐adrenoceptors can be studied in isolation. 2 Following exposure to various concentrations of phenoxybenzamine, no evidence was found for a selective inactivation of the postjunctional population of α 1 ‐adrenoceptors: the ‘rauwolscine‐resistant’ (α 1 ‐) and the ‘rauwolscine‐sensitive’ (α 2 ‐) responses to (—)‐noradrenaline were similarly affected. 3 However, in ‘receptor protection’ experiments following exposure to a combination of phenoxybenzamine and the selective α 2 ‐adrenoceptor antagonist rauwolscine, the remaining response to (—)‐noradrenaline appeared to be mediated by a single population of postjunctional α 2 ‐adrenoceptors: the response was insensitive to prazosin and rauwolscine was more potent than corynanthine. 4 Partial isolation of the α 1 ‐adrenoceptor population was attempted by pre‐exposure of the preparation to a combination of phenoxybenzamine and a selective α 1 ‐adrenoceptor antagonist, i.e. prazosin or YM‐12617. Following receptor protection, the inhibition produced by ‘selective’ concentrations of either of these α 1 ‐adrenoceptor antagonists were not significantly different from that observed in control preparations (no phenoxybenzamine). However, the selective α 2 ‐adrenoceptor antagonists rauwolscine and CH‐38083 were still able to inhibit part of the remaining responses to NA. This is interpreted as indicating that, in addition to protecting the putative postjunctional α 1 ‐adrenoceptors, these procedures fail to produce complete inactivation of postjunctional α 2 ‐adrenoceptors. 5 It is concluded that, although phenoxybenzamine appeared to be non‐selective for the two populations of postjunctional α‐adrenoceptors in the rabbit isolated saphenous vein, inclusion of a ‘selective’ concentration of a competitive antagonist during the inactivation period results in differing degrees of functional protection of each subtype. Pharmacological isolation was possible for α 2 ‐adrenoceptors but not convincingly for α 1 ‐adrenoceptors.