Striatal dopamine denervation decreases the GDP binding affinity in rat striatal membranes

The role of G-proteins in D-2 receptor supersensitivity was studied in striatal membranes from rats with unilateral 6-hydroxydopamine (6-OHDA) induced lesions of the nigral dopamine (DA) system. Thirteen months after the lesion the number of [H-3]raclopride binding sites was increased in the DA denervated striatum, but no changes in ligand binding affinities and in proportion of high-affinity agonist binding sites could be detected. The affinity of [S-35]GTP gamma S binding was unaltered after the striatal DA denervation, whereas the binding affinity of GDP was decreased in the DA denervated as compared to the intact striatum. It is proposed that the decrease in GDP binding affinity to D-2 DA receptor-coupled G proteins is an important factor in the D2 receptor supersensitivity following degeneration of the striatal DA terminals. (C) 2000 Lippincott Williams & Wilkins.