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Brain‐derived neurotrophic factor regulates the expression of D 1 dopamine receptors
Author(s) -
Do Thuy,
Kerr Bredford,
Kuzhikandathil Eldo V.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04249.x
Subject(s) - receptor , dopamine , neuroscience , dopamine receptor , neurotrophic factors , brain derived neurotrophic factor , biology , microbiology and biotechnology , biochemistry
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.