Modulation of high-affinity CNS dopamine D2 receptor by L-pro-L-leu-glycinamide (PLG) analogue 3(R)-(N-L-prolylamino)-2-oxo-1-pyrrolidineacetamide.

1. In our previous studies, we reported that one of the conformationally constrained analogues of PLG, 3(R)-(N-L-prolylamino)-2-oxo-1-pyrrolidineacetamide (PAOPA), was found to be extremely potent in enhancing the [3H]ADTN binding when membranes were preincubated with this compound. The PAOPA was without effect when directly added to assay tubes. In this study, the compound PAOPA was examined on agonist binding to high affinity state of the dopamine D2 receptor. 2. The potent analogue PAOPA was able to prevent the GTP-induced conversion of high affinity state of dopamine D2 receptor to low affinity state. 3. PLG analogue PAOPA modulates the affinity states of the dopamine D2 receptor possibly by affecting its interaction with the G-protein(s).