Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, Abe M, Shintani Y, Onda H, Nishimura O, Fujino M
Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki, 300-4293, Japan.
Biochem Biophys Res Commun. 2001 May 25;283(5):1013-8. doi: 10.1006/bbrc.2001.4893.
A DNA fragment encoding an amino acid sequence possessing common features to the G protein-coupled receptor (GPCR) superfamily was found in the human genomic sequence, and from this information, the full-length cDNA of a novel GPCR, designated SLT, was cloned from the human hippocampus cDNA library. SLT showed the highest homology to the melanin-concentrating hormone (MCH) receptor, SLC-1 (31.5% identity), and to a lesser extent, to the somatostatin (SST) receptor subtypes. MCH exhibited agonistic behavior when applied to the SLT-expressing CHO cells at subnanomolar doses whereas more than 200 known peptides, including SST and cortistatin, did not. These results indicated that MCH is the cognate ligand of the SLT receptor and that this newly cloned GPCR is the second subtype of the MCH receptor. Quantitative polymerase chain reaction analysis of the SLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues. The distribution of the SLT nearly overlapped that of SLC-1, suggesting that some of the neural functions of MCH may be mediated by both of these receptor subtypes.
在人类基因组序列中发现了一个编码具有G蛋白偶联受体（GPCR）超家族共同特征氨基酸序列的DNA片段，基于此信息，从人类海马体cDNA文库中克隆出一种名为SLT的新型GPCR的全长cDNA。SLT与促黑素细胞激素（MCH）受体SLC-1的同源性最高（同一性为31.5%），与生长抑素（SST）受体亚型的同源性较低。当以亚纳摩尔剂量应用于表达SLT的CHO细胞时，MCH表现出激动作用，而包括SST和可体松在内的200多种已知肽则没有这种作用。这些结果表明，MCH是SLT受体的同源配体，这种新克隆的GPCR是MCH受体的第二个亚型。对人类组织中SLT基因表达的定量聚合酶链反应分析表明，SLT受体主要在包括大脑皮层、杏仁核、海马体和胼胝体在内的脑区以及少数外周组织中表达。SLT的分布与SLC-1几乎重叠，这表明MCH的一些神经功能可能由这两种受体亚型共同介导。
