DIFFERENTIAL LOCALIZATION OF ALPHA-2-ADRENERGIC RECEPTOR SUBTYPES IN BRAIN

The pharmacological identification and characterization of subtypes of alpha-2-adrenergic receptors have been confirmed by molecular biological investigations. Using receptor autoradiographic techniques, it has been possible to show regions of the brain where alpha-2 agonist binding ([H-3]para-aminoclonidine) is preferentially labeling the presumed guaninenucleotide-sensitive, high-affinity conformations of the alpha-2 receptor. Careful examination of autoradiograms generated using the tritiated antagonists yohimbine, idazoxan, and rauwolscine also indicates some disparity in the regions occupied by these radiolabeled ligands. Inhibition of [H-3]rauwolscine binding with the subtype selective compounds, ARC-239, or oxymetazoline demonstrates that there are discrete regions of the brain where one receptor subtype predominates over the other. These studies indicate that previous investigations utilizing the agonist para-aminoclonidine as the ligand for obtaining labeling Of alpha-2 receptors have overlooked some regions of binding due to the subtype selectivity of this ligand. A more complete localization Of alpha-2-adrenergic receptors can be obtained using the tritiated antagonist rauwolscine, and the differential distribution of at least two subtypes of the alpha-2 receptor can be obtained by selective inhibition of this binding.