THE DOPAMINE-D2 RECEPTOR - 2 MOLECULAR-FORMS GENERATED BY ALTERNATIVE SPLICING
THE DOPAMINE-D2 RECEPTOR - 2 MOLECULAR-FORMS GENERATED BY ALTERNATIVE SPLICING
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DOI：
10.1002/j.1460-2075.1989.tb08585.x
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发表时间：
1989-12-20
期刊：
影响因子：
11.4
通讯作者：
SEEBURG, PH
中科院分区：
文献类型：
--
作者：
DALTOSO, R;SOMMER, B;SEEBURG, PH
克隆的人多巴胺D2受体cDNA分离自垂体cDNA文库，并发现编码一个额外的29个氨基酸残基之间的跨膜区5和6相对于先前描述的大鼠脑D2受体的预测的胞内域。从聚合酶链反应以及原位杂交的结果显示，编码两种受体形式的mRNA存在于垂体和大脑的大鼠和人。较大的形式是占主导地位的，在这些组织中，如在大鼠中所示，表达的多巴胺能和多巴胺感受神经元。对人类基因的分析表明，额外的肽序列由单独的外显子编码。因此，这两种受体形式是通过差异剪接产生的，可能允许与不同的G蛋白偶联。在培养的哺乳动物细胞中表达的两种受体均以高亲和力结合[3H]螺哌隆并抑制腺苷酸环化酶，正如D2受体亚型的预期。
Cloned human dopamine D2 receptor cDNA was isolated from a pituitary cDNA library and found to encode an additional 29 amino acid residues in the predicted intracellular domain between transmembrane regions 5 and 6 relative to a previously described rat brain D2 receptor. Results from polymerase chain reactions as well as in situ hybridization revealed that mRNA encoding both receptor forms is present in pituitary and brain of both rat and man. The larger form was predominant in these tissues and, as shown in the rat, expressed by dopaminergic and dopaminoceptive neurons. Analysis of the human gene showed that the additional peptide sequence is encoded by a separate exon. Hence, the two receptor forms are generated by differential splicing possibly to permit coupling to different G proteins. Both receptors expressed in cultured mammalian cells bind [3H]spiperone with high affinity and inhibit adenylyl cyclase, as expected of the D2 receptor subtype.