An attempt at selective protection from phenoxybenzamine of postjunctional α-adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein

Daly, C.J. , Dunn, W.R., McGrath, J.C. and Wilson, V.G. (1988) An attempt at selective protection from phenoxybenzamine of postjunctional α-adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein. British Journal of Pharmacology, 95(2), pp. 501-511. (doi: 10.1111/j.1476-5381.1988.tb11670.x)

Abstract

1: An attempt has been made, with the irreversible α-adrenoceptor antagonist phenoxybenzamine, to find the conditions under which postjunctional α1-adrenoceptors in the rabbit isolated saphenous vein can be inactivated, such that postjunctional α2-adrenoceptors can be studied in isolation.<p></p> 2: Following exposure to various concentrations of phenoxybenzamine, no evidence was found for a selective inactivation of the postjunctional population of α1-adrenoceptors: the ‘rauwolscine-resistant’ (α1-) and the ‘rauwolscine-sensitive’ (α2-) responses to (—)-noradrenaline were similarly affected.<p></p> 3: However, in ‘receptor protection’ experiments following exposure to a combination of phenoxybenzamine and the selective α2-adrenoceptor antagonist rauwolscine, the remaining response to (—)-noradrenaline appeared to be mediated by a single population of postjunctional α2-adrenoceptors: the response was insensitive to prazosin and rauwolscine was more potent than corynanthine.<p></p> 4: Partial isolation of the α1-adrenoceptor population was attempted by pre-exposure of the preparation to a combination of phenoxybenzamine and a selective α1-adrenoceptor antagonist, i.e. prazosin or YM-12617. Following receptor protection, the inhibition produced by ‘selective’ concentrations of either of these α1-adrenoceptor antagonists were not significantly different from that observed in control preparations (no phenoxybenzamine). However, the selective α2-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 α1-adrenoceptors, these procedures fail to produce complete inactivation of postjunctional α2-adrenoceptors.<p></p> 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 α2-adrenoceptors but not convincingly for α1-adrenoceptors.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGrath, Professor John and Daly, Professor Craig
• Authors: Daly, C.J., Dunn, W.R., McGrath, J.C., and Wilson, V.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: British Journal of Pharmacology
• Publisher: John Wiley & Sons, Inc.
• ISSN: 0007-1188
• ISSN (Online): 1476-5381