Shan L, Qiao X, Crona J H, Behan J, Wang S, Laz T, Bayne M, Gustafson E L, Monsma F J, Hedrick J A
Human Genome Research and Cardiovascular/Central Nervous System Research, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
J Biol Chem. 2000 Dec 15;275(50):39482-6. doi: 10.1074/jbc.C000522200.
Neuromedin U is a neuropeptide prominently expressed in the upper gastrointestinal tract and central nervous system. Recently, GPR66/FM-3 (NmU-R1) was identified as a specific receptor for neuromedin U. A BLAST search of the GenBank(TM) genomic database using the NmU-R1 cDNA sequence revealed a human genomic fragment encoding a G protein-coupled receptor that we designated NmU-R2 based on its homology to NmU-R1. The full-length NmU-R2 cDNA was subsequently cloned, stably expressed in 293 cells, and shown to mobilize intracellular calcium in response to neuromedin U. This response was dose-dependent (EC(50) = 5 nm) and specific in that other neuromedins did not induce a calcium flux in receptor-transfected cells. Expression analysis of human NmU-R2 demonstrated its mRNA to be most highly expressed in central nervous system tissues. Based on these data, we conclude that NmU-R2 is a novel neuromedin U receptor subtype that is likely to mediate central nervous system-specific neuromedin U effects.
神经介素U是一种主要在上消化道和中枢神经系统表达的神经肽。最近，GPR66/FM-3（NmU-R1）被鉴定为神经介素U的特异性受体。使用NmU-R1 cDNA序列对GenBank™基因组数据库进行BLAST搜索，发现了一个编码G蛋白偶联受体的人类基因组片段，基于其与NmU-R1的同源性，我们将其命名为NmU-R2。随后克隆了全长NmU-R2 cDNA，并在293细胞中稳定表达，结果显示其可响应神经介素U而动员细胞内钙。这种反应具有剂量依赖性（EC(50)=5 nM），并且具有特异性，即其他神经介素不会在受体转染细胞中诱导钙通量。人NmU-R2的表达分析表明其mRNA在中枢神经系统组织中表达最高。基于这些数据，我们得出结论，NmU-R2是一种新型神经介素U受体亚型，可能介导中枢神经系统特异性神经介素U效应。
