Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors
Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors
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DOI：
10.1111/j.1471-4159.2006.04249.x
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发表时间：
2007-01-01
影响因子：
4.7
通讯作者：
Kuzhikandathil, Eldo V.
中科院分区：
文献类型：
--
作者：
Do, Thuy;Kerr, Bredford;Kuzhikandathil, Eldo V.
我们以前已经证明，CAD的儿茶酚胺能神经元细胞系是一个适当的模型系统，研究D-1多巴胺受体表达的调节。在这份报告中，我们表明，脑源性神经营养因子（BDNF）上调D-1多巴胺受体在CAD细胞的表达。此外，通过比较野生型、杂合型和纯合型trkB敲除小鼠中D-1受体mRNA的表达，我们表明TrkB受体信号传导上调体内D-1受体表达。在表达TrkB受体的CAD细胞中，BDNF以时间和剂量依赖性的方式增加D-1受体mRNA，早在3 h时观察到10 ng/mL BDNF使D-1受体mRNA增加4倍。使用不同种类和浓度的激酶抑制剂，我们确定BDNF诱导的D-1受体mRNA的增加是由磷脂酰肌醇3-激酶信号通路介导的。这种增加需要新的转录和蛋白质合成，因为它分别被放线菌素D和环己酰胺阻断。启动子缺失分析鉴定了介导BDNF作用所必需的D-1启动子区域。这些结果为D-1多巴胺受体表达受BDNF及其信号通路调控提供了新的证据。
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.