An attempt at selective protection from phenoxybenzamine of postjunctional alpha-adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein.
1. An attempt has been made, with the irreversible alpha-adrenoceptor antagonist phenoxybenzamine, to find the conditions under which postjunctional alpha 1-adrenoceptors in the rabbit isolated saphenous vein can be inactivated, such that postjunctional alpha 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 alpha 1-adrenoceptors: the "rauwolscine-resistant' (alpha 1-) and the "rauwolscine-sensitive' (alpha 2-) responses to (--)-noradrenaline were similarly affected. 3. However, in "receptor protection' experiments following exposure to a combination of phenoxybenzamine and the selective alpha 2-adrenoceptor antagonist rauwolscine, the remaining response to (--)-noradrenaline appeared to be mediated by a single population of postjunctional alpha 2-adrenoceptors: the response was insensitive to prazosin and rauwolscine was more potent than corynanthine. 4. Partial isolation of the alpha 1-adrenoceptor population was attempted by pre-exposure of the preparation to a combination of phenoxybenzamine and a selective alpha 1-adrenoceptor antagonist, i.e. prazosin or YM-12617. Following receptor protection, the inhibition produced by "selective' concentrations of either of these alpha 1-adrenoceptor antagonists were not significantly different from that observed in control preparations (no phenoxybenzamine). However, the selective alpha 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 alpha 1-adrenoceptors, these procedures fail to produce complete inactivation of postjunctional alpha 2-adrenoceptors. 5. It is concluded that, although phenoxybenzamine appeared to be non-selective for the two populations of postjunctional alpha-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 alpha 2-adrenoceptors but not convincingly for alpha 1-adrenoceptors.
Daly
C J
CJ
Autonomic Physiology Unit, University of Glasgow, Scotland.
Dunn
W R
WR
McGrath
J C
JC
Wilson
V G
VG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D009638:Norepinephrine; D010643:Phenoxybenzamine; D011224:Prazosin; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; D015016:Yohimbine; C044648:YM 12617; D000096926:Benzenesulfonamides