南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (06): 715-718.

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多巴胺受体在可卡因诱导的转录因子CREB活化中的作用(英文)

刘怒云; 张琳; 王小宁; 张璐;   

  1. 南方医科大学生物技术学院分子免疫研究所; 南方医科大学广东省功能蛋白质组学重点实验室重大疾病的转录组与蛋白质组学教育部重点实验室; 南方医科大学广东省功能蛋白质组学重点实验室重大疾病的转录组与蛋白质组学教育部重点实验室 广东广州510515; 广东广州510515;
  • 出版日期:2006-06-20 发布日期:2006-06-20
  • 基金资助:
    SupportedbyScienceTechnologyResearchProjectofGuangdong(2005B50301010)andNaturalScienceFoundationofGuangdong(40204411)

Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation

LIU Nu-yun1, ZHANG Lin2, WANG Xiao-ning1, ZHANG Lu2 1Institute of Molecular Immunology, Southern Medical University, Guangzhou 510515, China; 2Department of Pathophysiology, Key Laboratory of Functional Proteomics of Guangdong Province, Key Laboratory for Transcriptomics and Proteomics of Ministry of Education, Southern Medical University, Guangzhou 510515, China   

  1. 南方医科大学生物技术学院分子免疫研究所; 南方医科大学广东省功能蛋白质组学重点实验室重大疾病的转录组与蛋白质组学教育部重点实验室; 南方医科大学广东省功能蛋白质组学重点实验室重大疾病的转录组与蛋白质组学教育部重点实验室 广东广州510515; 广东广州510515;
  • Online:2006-06-20 Published:2006-06-20

摘要: 目的研究多巴胺受体在可卡因诱导的转录因子CREB磷酸化活化中的调控作用。方法采用D1和D3多巴胺受体抑制剂,应用Westernblotting检测D1与D3多巴胺受体在可卡因诱导的cAMP反应元件结合蛋白(CREB)磷酸化活化中的作用及D1和D3多巴胺受体抑制剂本身对CREB磷酸化活化的影响,进一步应用Westernblotting检测细胞外信号调节激酶(ERK)在CREB磷酸化活化中的作用。结果D1多巴胺受体抑制剂阻止可卡因诱导的CREB磷酸化活化,而D3多巴胺受体抑制剂促进可卡因诱导的CREB磷酸化活化,D1和D3多巴胺受体抑制剂本身不能诱导CREB磷酸化活化。MEK的特异性抑制剂SL327可以抑制可卡因诱导的CREB磷酸化活化。结论D1和D3多巴胺受体对CREB的磷酸化活化起反式调控作用,并且这种反式调控作用依赖于ERK信号通路。 

Abstract: Objective To study the role of dopamine receptors in the regulation of the activity of transcription factor cAMP response element-binding protein (CREB) after cocaine treatment. Methods By using dopamine receptor antagonists SCH23390 and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after cocaine treatment and role of extracellular signal-regulated kinase (ERK) in cocaine-induced CREB activation were examined by Western blotting, which was also employed for determination of the effect of SCH23390 and nafadotride on CREB activation. Results D1 receptor antagonist could inhibit cocaine-induced CREB activation, while D3 receptor antagonist enhanced cocaine-induced CREB activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB activation. Conclusion D1 and D3 dopamine receptors can oppositely regulate CREB activation after cocaine treatment and this regulation depends on ERK signaling pathway. 

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