Zhou Q Y, Grandy D K, Thambi L, Kushner J A, Van Tol H H, Cone R, Pribnow D, Salon J, Bunzow J R, Civelli O
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Nature. 1990 Sep 6;347(6288):76-80. doi: 10.1038/347076a0.
The importance of the dopaminergic system in brain function has been emphasized by its association with neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. On the basis of their biochemical and pharmacological characteristics, dopamine receptors are classified into D1 and D2 subtypes. As the most abundant dopamine receptor in the central nervous system, D1 receptors seem to mediate some behavioural responses, modulate activity of D2 dopamine receptors, and regulate neuron growth and differentiation. The D dopamine receptor has been cloned by low-stringency screening. We report here the cloning of human and rat D1 dopamine receptors by applying an approach based on the polymerase chain reaction. The cloned human D1 dopamine receptor has been characterized on the basis of four criteria: the deduced amino-acid sequence, which reveals that it is a G protein-coupled receptor; the tissue distribution of its messenger RNA, which is compatible with that of the D1 dopamine receptor; its pharmacological profile when transfected into COS-7 cells; and its ability to stimulate the accumulation of cyclic AMP in human 293 cells.
多巴胺能系统与帕金森病和精神分裂症等神经和精神疾病相关,这凸显了其在脑功能中的重要性。根据其生化和药理特性,多巴胺受体可分为D1和D2亚型。作为中枢神经系统中含量最丰富的多巴胺受体,D1受体似乎介导某些行为反应,调节D2多巴胺受体的活性,并调节神经元的生长和分化。D多巴胺受体已通过低严谨度筛选进行克隆。我们在此报告通过应用基于聚合酶链反应的方法克隆人及大鼠D1多巴胺受体。已根据四个标准对克隆的人D1多巴胺受体进行了表征:推导的氨基酸序列,表明它是一种G蛋白偶联受体;其信使RNA的组织分布,与D1多巴胺受体的分布相符;转染到COS-7细胞后的药理特性;以及其刺激人293细胞中环状AMP积累的能力。