Howard A D, Wang R, Pong S S, Mellin T N, Strack A, Guan X M, Zeng Z, Williams D L, Feighner S D, Nunes C N, Murphy B, Stair J N, Yu H, Jiang Q, Clements M K, Tan C P, McKee K K, Hreniuk D L, McDonald T P, Lynch K R, Evans J F, Austin C P, Caskey C T, Van der Ploeg L H, Liu Q
Department of Metabolic Disorders, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Nature. 2000 Jul 6;406(6791):70-4. doi: 10.1038/35017610.
Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.
神经介素U（NMU）是一种对平滑肌具有强大活性的神经肽，最初从猪脊髓中分离出来，后来在其他物种中也有发现。它广泛分布于肠道和中枢神经系统。NMU的外周活性包括刺激平滑肌、升高血压、改变肠道离子转运、控制局部血流以及调节肾上腺皮质功能。尚未从分子层面鉴定出NMU受体。在此我们表明，先前描述的孤儿G蛋白偶联受体FM - 3（参考文献15）和新发现的一种受体（FM - 4）是NMU的同源受体。FM - 3被命名为NMU1R，在外周组织中大量表达，而FM - 4被命名为NMU2R，在大脑的特定区域表达。NMU在大鼠大脑的腹内侧下丘脑表达，禁食后其水平显著降低。脑室内注射NMU可显著抑制大鼠的食物摄入。这些发现为NMU的生化活性提供了分子基础，可能表明NMU参与了进食的中枢控制。
