[3H]Clonidine, a α-noradrenergic agonist, and [3H]WB-4101, a benzodioxan derivative α-antagonist, bind with high affinity and selectivity to membranes of rat brain in a fashion indicating that they label postsynaptic α-noradrenergic receptors. Binding for both ligands is saturable with KD values of 5 nM and 0.6 nM respectively for clonidine and WB-4101. The relative affinities of a series of phenylethylamines for binding sites corresponds well with their relative influences at α-receptors. Binding of both [3H]-ligands is stereoselective with about a 50 fold preference for (-)-norepinephrine. Of a series of ergot alkaloids, only those with known α-receptor activity have high affinities for the binding sites. Binding does not involve pre-synaptic norepinephrine nerve endings, because after an 80% depletion of endogenous norepinephrine by treatment with 6-hydroxydopamine, no decrease can be detected in [3H]clonidine and [3H]WB-4101 binding. α-Agonists have much higher affinities for [3H]clonidine than [3H]WB-4101 sites, while the reverse holds true for α-antagonists. Mixed agonist-antagonist ergots have similar affinities for binding of the two [3H]ligands. These data suggest that [3H]clonidine and [3H]WB-4101 respectively label distinct agonist and antagonist states of the α-receptor.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)