Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors.

We have previously demonstrated that the CAD catecholaminergic neuronal cell line is an appropriate model system to study the regulation of D(1) dopamine receptor expression. In this report, we show that brain-derived neurotrophic factor (BDNF) up-regulates the expression of D(1) dopamine receptor in CAD cells. In addition, by comparing D(1) receptor mRNA expression in wild-type, heterozygous and homozygous trkB knockout mice, we show that TrkB receptor signaling up-regulates D(1) receptor expression in vivo. In CAD cells expressing the TrkB receptor, BDNF increased D(1) receptor mRNA in a time- and dose-dependent manner with a fourfold increase in D(1) receptor mRNA observed as early as 3 h with 10 ng/mL of BDNF. Using different classes and concentrations of kinase inhibitors, we determined that BDNF-induced increase of D(1) receptor mRNA is mediated by the phosphatidylinositol 3-kinase signaling pathway. The increase required both new transcription and protein synthesis, as it was blocked by actinomycin D and cyclohexamide, respectively. Promoter deletion analysis identified a D(1) promoter region necessary for mediating the effect of BDNF. These results provide novel evidence that D(1) dopamine receptor expression is regulated by BDNF and its signaling pathway.