Identification of neuromedin S and its possible role in the mammalian circadian oscillator system

Identification of neuromedin S and its possible role in the mammalian circadian oscillator system
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DOI:
10.1038/sj.emboj.7600526
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发表时间:
2005-01-26
期刊:
影响因子:
11.4
通讯作者:
Kangawa, K
Kangawa, K
中科院分区:
生物学1区
文献类型:
--
作者:
Mori, K;Miyazato, M;Kangawa, K

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神经肽的发现使人们对某些生理现象的新调节机制有了更多的了解。在这里,我们确定了一种新的神经肽的36个氨基酸残基在大鼠脑中作为一个内源性配体的孤儿G蛋白偶联受体FM-4/TGR-1,这是迄今为止被确定为神经介肽U(NMU)受体,并指定这种肽“神经介肽S(NMS)”,因为它是专门表达在视交叉上核(SCN)的下丘脑。NMS与NMU共享C端核心结构。NMS前体含有另一种新的肽。NMS mRNA在中枢神经系统、脾脏和睾丸中高度表达。在大鼠脑中,NMS表达仅限于SCN的核心,并且在光/暗循环下具有昼夜高峰,但在恒定黑暗下保持稳定。大鼠侧脑室注射NMS可激活SCN神经元,并诱导运动活动昼夜节律中的非光型相移。这些发现表明,在SCN的NMS涉及通过自分泌和/或旁分泌作用的昼夜节律的调节。
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.