Hyman S E, Cole R L, Konradi C, Kosofsky B E
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Charlestown 02129, USA.
Chem Senses. 1995 Apr;20(2):257-60. doi: 10.1093/chemse/20.2.257.
Transcriptional regulation is an important mechanism by which neurons adapt to environmental stimuli. The indirect dopamine agonists, amphetamine and cocaine have been shown to induce expression of immediate early genes, such as c-fos, and neuropeptide genes, such as prodynorphin in the rat striatum. Here we show that phosphorylation of transcription factor CREB is a critical early event coupling dopamine stimulation to gene regulation. CREB interacts with functional regulatory elements in both the c-fos and prodynorphin genes, and is phosphorylated in response to dopamine in a D1 dopamine receptor-dependent manner. In addition, we show by intra-striatal injection of antisense oligonucleotides directed against CREB mRNA, that CREB protein is required for c-fos induction by amphetamine.
转录调控是神经元适应环境刺激的一种重要机制。间接多巴胺激动剂苯丙胺和可卡因已被证明可诱导大鼠纹状体中即刻早期基因（如c-fos）以及神经肽基因（如前强啡肽原）的表达。在此我们表明，转录因子CREB的磷酸化是将多巴胺刺激与基因调控相偶联的一个关键早期事件。CREB与c-fos和前强啡肽原基因中的功能性调控元件相互作用，并以D1多巴胺受体依赖性方式响应多巴胺而被磷酸化。此外，我们通过向纹状体内注射针对CREB mRNA的反义寡核苷酸表明，CREB蛋白是苯丙胺诱导c-fos所必需的。
