Modulation of [S-35]GTP gamma S binding to Chinese hamster ovary cell membranes by D-2(short) dopamine receptors

Rat dopamine D-2short expressed in Chinese hamster ovary (CHO) cells were c haracterized by means of activation of [S-35]-guanosine 5'-O-(gamma-thiotri phosphate) ([S-35]GTP gamma S) binding and inhibition of [H-3]raclopride bi nding. Among 18 dopaminergic ligands studied dopamine, NPA, apomorphine and quinpirole were full agonists in activation of [S-35]GTP gamma S binding, while seven ligands were partial agonists with efficacies from 16 to 69% of the effect of dopamine and seven ligands were antagonists having no effect on the basal level of [S-35]GTP gamma S binding, but inhibited dopamine-de pendent activation in a dose-response manner. Despite the different efficac ies, the potencies of all 18 ligands to modulate [S-35]GTP gamma S binding revealed a good correlation with their potencies to inhibit [H-3]raclopride binding in the CHO cell membranes. This indicates that the binding of the ligand to the receptor determines its potency, but has no direct correlatio n with its intrinsic activity. (C) 2000 Elsevier Science Ireland Ltd. All r ights reserved.