Serotonergic agonists behave as partial agonists at the dopamine D-2 receptor

RAT dopamine D-2short receptors expressed in CHO cells were characterized b y activation of [S-35]GTP gamma S binding. There were no significant differ ences between the maximal effects seen in activation of [S-35]GTP gamma S b inding caused by dopaminergic agonists, but the effects of 5-MT, 8OH-DPAT a nd 5-methoxytryptamine amounted to 47 +/- 7%, 43 +/- 5% and 70 +/- 7% of th e dopamine effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited activations of both types of ligands with equal potency (pA(2) = 8.9 +/- 0.1), indicating that only one type of receptor is involved. In com petition with [H-3]raclopride binding, dopaminergic agonists showed 53 +/- 2% of the binding sites in the GTP-dependent high-affinity state, whereas 5 -HT showed only 20 +/- 3%. Taken together the results indicate that seroton ergic agonists behave as typical partial agonists for D-2 receptors with po tential antiparkinsonian activity. (C) 1999 Lippincott Williams & Wilkins.