Lachowicz J E, Sibley D R
Experimental Therapeutics Branch, National Institutes of Health, Bethesda, Maryland, 20892-1406, USA.
Biochem Biophys Res Commun. 1997 Aug 18;237(2):394-9. doi: 10.1006/bbrc.1997.7146.
We have sought to determine which area of the D2 dopamine receptor's third intracellular loop contributes to G-protein coupling by constructing reciprocal chimeric D2/D3 receptors with fusion points near the center of the third intracellular loop. Both receptor chimeras were expressed equally well in Chinese Hamster Ovary (CHO) cells and exhibited ligand binding properties similar to those of the wild type receptors. Surprisingly, both of the D2/D3 receptor chimeras were able to effectively inhibit adenylyl cyclase activity to almost the same extent as that seen with the D2 receptor whereas the D3 receptor was without effect. These results suggest that the D2 receptor possesses two redundant and independent domains for G-protein coupling and inhibition of adenylyl cyclase activity.
我们试图通过构建在第三个细胞内环中心附近有融合点的相互嵌合的D2/D3受体，来确定D2多巴胺受体第三个细胞内环的哪个区域有助于与G蛋白偶联。两种受体嵌合体在中国仓鼠卵巢（CHO）细胞中表达效果相同，并且表现出与野生型受体相似的配体结合特性。令人惊讶的是，两种D2/D3受体嵌合体都能够有效抑制腺苷酸环化酶活性，其程度几乎与D2受体相同，而D3受体则无此作用。这些结果表明，D2受体具有两个冗余且独立的结构域用于与G蛋白偶联以及抑制腺苷酸环化酶活性。
