We have previously shown (SFN 2002 Abstract #542.6) that D3 dopamine receptors (D3DARs) and AMPA receptor subunits can be co-immunoprecipitated from HEK293T cells. These effects were specific and suggested that D3 and AMPA receptors may form hetero-oligomers when expressed in the same cell. We have now investigated the functional consequences of these receptor-receptor interactions using intact cells. Using radioligand binding assays, we found that co-expression of the GluR2 or GluR3 subunits resulted in a 25-50% decrement in D3DAR expression levels. To examine D3DAR function, it was necessary to co-transfect adenylyl cyclase type V in the cells and then examine D3DAR-mediated inhibition of forskolin-stimulated cAMP accumulation. Both dopamine and quinpirole inhibited the adenylyl cyclase activity in a dose-dependent fashion. Co-expression of GluR2 with the D3DAR resulted in a 4-6 fold rightward shift in the agonist dose-response curves (increase in EC50) without a major effect on the maximum response. Int...