DISTINCT ALPHA-NORADRENERGIC RECEPTORS DIFFERENTIATED BY BINDING AND PHYSIOLOGICAL RELATIONSHIPS

In brain and peripheral tissues the α-noradrenergic agonists 3H-clonidine, 3H-epinephrine and 3H-norepinephrine label sites which are distinct from and do not interconvert with those labeled by the α-noradrenergic antagonist 3H-WB-4101 (2-([2', 6'-dimethoxy]-phenoxyethylamino) methylbenzodioxane). In general agonists have higher affinity for sites labeled by the 3H-agonists while antagonists prefer sites labeled by 3H-WB-4101, though ergots and the α-antagonist phentolamine have similar affinities for the two sites. Peripheral tissues vary in relative numbers of 3H-agonist and 3H-WB-4101 sites with heart and vas deferens having almost exclusively 3H-WB-4101 sites, the rabbit duodenum only 3H-agonist sites, while salivary gland, spleen and cerebral cortex display similar numbers of both sites. The two sites appear to be postsynaptic since 6-hydroxydopamine treatment does not reduce their numbers. In vas deferens, heart and spleen pharmacological potencies of α-agonists and antagonists correlate closely with affinities for 3H-WB-4101 but not 3H-clonidine sites, while potencies in rabbit duodenum correlate with affinities for 3H-clonidine but not 3H-WB-4101 sites. The correspondence of separate binding sites with distinctive patterns of physiological responses indicates the existence of two discrete types of postsynaptic α-receptors. We propose to designate sites labeled by WB-4101 as α-1 receptors and those labeled by 3H-clonidine, 3H-norepinephrine and 3H-epinephrine as α-2 receptors. Drug potencies at α-2 binding sites resemble their affinities for presynaptic α-noradrenergic autoreceptors. © 1979.