RT Journal Article SR Electronic T1 Binding Characteristics of a Radiolabeled Agonist and Antagonist at Central Nervous System Alpha Noradrenergic Receptors JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 454 OP 473 VO 13 IS 3 A1 DAVID C. U’PRICHARD A1 DAVID A. GREENBERG A1 SOLOMON H. SNYDER YR 1977 UL http://molpharm.aspetjournals.org/content/13/3/454.abstract AB Binding of the alpha noradrenergic agonist [3H]clonidine and the alpha antagonist [3H]WB-4101 (2-([2',6'-dimethoxy]phenoxyethylamino)methylbenzodioxan) to rat brain membranes exhibits characteristics expected of alpha receptors for norepinephrine. Binding of both [3H]ligands is saturable, with KD values of 5.8 nM and 0.48 nM for [3H]clonidine and [3H]WB-4101, respectively. A series of catecholamines inhibits the binding of both ligands with the potency order epinephrine > norepinephrine >> isoproterenol, corresponding to the relative activities of these agents at alpha receptors in the periphery. Competition for binding is stereoselective, with (-) isomers of phenylethanolamines many times more potent than the corresponding (+) isomers. Classical alpha antagonists inhibit binding of both ligands at low concentrations, but beta antagonists are much weaker. Alpha agonists are more potent in displacing [3H]clonidine than [3H]WB-4101 binding, while alpha antagonists compete more avidly for [3H]WB-4101 sites. Partial agonist ergot alkaloids display similar affinities for the binding sites of both [3H]ligands. These findings may be explained by the existence of discrete agonist and antagonist states of the alpha receptor, which preferentially bind [3H]clonidine and [3H]WB-4101, respectively. Regional variations in the binding of both [3H]ligands in the brain are not pronounced, although levels tend to be highest in hypothalamus and cerebral cortex and lowest in cerebellum. Treatment with 6-hydroxydopamine fails to decrease the binding of either [3H]ligand, suggesting that binding occurs to postsynaptic sites. ACKNOWLEDGMENT We thank Mr. Stephen J. Peroutka for his skillful technical assistance.