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

Abstract

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 D1 receptor mRNA in a time- and dose-dependent manner with a fourfold increase in D1 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 D1 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 D1 promoter region necessary for mediating the effect of BDNF. These results provide novel evidence that D1 dopamine receptor expression is regulated by BDNF and its signaling pathway. © 2007 The Authors.