Article
- The EMBO Journal (2005) 24, 325 - 335
- doi:10.1038/sj.emboj.7600526
Published online: 6 January 2005
Subject Categories:
Identification of neuromedin S and its possible role in the mammalian circadian oscillator system
Kenji Mori1, Mikiya Miyazato1, Takanori Ida2, Noboru Murakami2, Ryota Serino3, Yoichi Ueta3, Masayasu Kojima4 and Kenji Kangawa1
- Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka, Japan
- Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
- Division of Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan
Correspondence to:
Kenji Kangawa, Department of Biochemistry, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. Tel.: +81 6 6833 5012; Fax: +81 6 6835 5402; E-mail: kangawa@ri.ncvc.go.jp
Received 5 July 2004; Accepted 26 November 2004
Abstract
The discovery of neuropeptides has resulted in an increased understanding of novel regulatory mechanisms of certain physiological phenomena. Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan G protein-coupled receptor FM-4/TGR-1, which was identified to date as the neuromedin U (NMU) receptor, and designate this peptide 'neuromedin S (NMS)' because it is specifically expressed in the suprachiasmatic nuclei (SCN) of the hypothalamus. NMS shares a C-terminal core structure with NMU. The NMS precursor contains another novel peptide. NMS mRNA is highly expressed in the central nervous system, spleen and testis. In rat brain, NMS expression is restricted to the core of the SCN and has a diurnal peak under light/dark cycling, but remains stable under constant darkness. Intracerebroventricular administration of NMS in rats activates SCN neurons and induces nonphotic type phase shifts in the circadian rhythm of locomotor activity. These findings suggest that NMS in the SCN is implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.
Keywords:
- circadian rhythm,
- endogenous ligand,
- neuropeptide,
- orphan G protein-coupled receptor,
- suprachiasmatic nucleus
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