Sunahara R K, Guan H C, O'Dowd B F, Seeman P, Laurier L G, Ng G, George S R, Torchia J, Van Tol H H, Niznik H B
Department of Pharmacology, University of Toronto, Ontario, Canada.
Nature. 1991 Apr 18;350(6319):614-9. doi: 10.1038/350614a0.
Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.
多巴胺受体属于通过鸟嘌呤核苷酸结合（G）蛋白发挥生物学效应的受体超家族。已鉴定出两种主要的多巴胺受体亚型，即D1和D2，它们在药理学和生化特性上有所不同。D1刺激腺苷酸环化酶活性，而D2抑制它。这两种受体都是用于治疗许多精神运动疾病（包括帕金森病和精神分裂症）的药物的主要靶点。虽然多巴胺D1受体已被克隆，但生化和行为学数据表明存在多巴胺D1样受体，它们要么不与腺苷酸环化酶相连，要么表现出不同的药理活性。我们在此报告克隆了一个编码与克隆的D1受体具有高度同源性的477个氨基酸蛋白质的基因。该受体称为D5，与克隆的D1受体具有相似的药理学特征结合药物，但对内源性激动剂多巴胺的亲和力高10倍。与D1一样，多巴胺D5受体刺激腺苷酸环化酶活性。Northern印迹和原位杂交分析表明该受体是神经元特异性的，主要定位于脑的边缘区域；在肾、肝、心或甲状旁腺中未检测到信使RNA。具有这些特征的多巴胺D1样受体的存在尚未被预测，可能代表多巴胺介导的事件和D2受体活性调节的另一种途径。
