We have previously shown (SFN 2001 Abstract #379.5) that D2/D3 dopamine receptors directly interact with GRIP, a PDZ domain-containing protein that interacts with GluR2/3 AMPA receptor subunits. GRIP functions as a scaffolding protein linking AMPA receptors and other signaling proteins into macromolecular complexes within postsynaptic membranes. Given this, and the fact that D2-like and AMPA receptors show cellular co-localization in the CNS (Synapse 26:400, 1997), we wondered if D2 or D3 receptors might form heterodimers with AMPA receptors, perhaps in a GRIP-facilitated fashion. As an initial test of this hypothesis, we co-expressed a FLAG-tagged D2 receptor or a c-myc-tagged D3 receptor with either GluR1, GluR2 or GluR4 AMPA receptor subunits in HEK293T cells. Radioligand binding assays confirmed the expression of the dopamine receptors while immunoblots confirmed the expression of the AMPA receptors. The cells were detergent-solubilized and the D2 or D3 receptors were immunoprecipitated with either ant...