Brain-derived neurotrophic factor regulates the expression of D-1 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.