MULTIPLE D2 DOPAMINE-RECEPTORS PRODUCED BY ALTERNATIVE RNA SPLICING
MULTIPLE D2 DOPAMINE-RECEPTORS PRODUCED BY ALTERNATIVE RNA SPLICING
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DOI：
10.1038/342926a0
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发表时间：
1989-12-21
期刊：
影响因子：
64.8
通讯作者：
SIBLEY, DR
中科院分区：
文献类型：
--
作者：
MONSMA, FJ;MCVITTIE, LD;SIBLEY, DR
多巴胺受体属于一大类神经递质和激素受体，通过鸟嘌呤核苷酸结合调节蛋白（G蛋白）与其信号转导途径相连。药理学、生物化学和生理学标准已被用于定义多巴胺受体的两个亚类，称为D1和D2。D1受体激活腺苷酸环化酶2并与G调节蛋白3偶联。相比之下，D2受体的激活导致各种反应，包括腺苷酸环化酶的抑制4，磷脂酰肌醇周转的抑制5，K+通道活性的增加6和Ca2+动员的抑制7。尽管D2受体已被证明与G1和G0相关蛋白3共同纯化8，9并在功能上重建10，11，但将D2受体与这些反应联系起来的G蛋白尚未被鉴定。D2受体激活引起的反应的多样性可以反映多种D2受体亚型的存在，最近克隆的编码大鼠D2受体的互补DNA 12促进了D2受体亚型的鉴定。该受体与G蛋白偶联受体超家族的其他成员具有相当大的氨基酸同源性12，13。在这里，我们报告的识别和克隆的cDNA编码的RNA剪接变异体的大鼠D2受体cDNA 12。该cDNA编码主要在脑中表达的受体同种型，并且在第三胞质环中含有额外的29个氨基酸，该区域被认为参与G蛋白偶联。
DOPAMINE receptors belong to a large class of neurotransmitter and hormone receptors that are linked to their signal transduction pathways through guanine nucleotide binding regulatory proteins (G proteins). Pharmacological, biochemical and physiological criteria have been used to define two subcategories of dopamine receptors1referred to as D1and D2. D1receptors activate adenylyl cyclase2and are coupled with the Gsregulatory protein3. By contrast, activation of D2receptors results in various responses including inhibition of adenylyl cyclase4, inhibition of phosphatidylinositol turnover5, increase in K+channel activity6and inhibition of Ca2+mobilization7. The G protein(s) linking the D2receptors to these responses have not been identified, although D2receptors have been shown to both copurify8,9and functionally reconstitute10,11with both Giand Gorelated proteins3. The diversity of responses elicited by D2-receptor activation could reflect the existence of multiple D2receptor subtypes, the identification of which is facilitated by the recent cloning of a complementary DNA encoding a rat D2receptor12. This receptor exhibits considerable amino-acid homology with other members of the G protein-coupled receptor superfamily12,13. Here we report the identification and cloning of a cDNA encoding an RNA splice variant of the rat D2receptor cDNA12. This cDNA codes for a receptor isoform which is predominantly expressed in the brain, and contains an additional 29 amino acids in the third cytoplasmic loop, a region believed to be involved in G protein coupling.