Functional analysis and search for novel bioactive peptides associated with regulation of feeding behavior and energy balance.

功能分析和寻找与摄食行为和能量平衡调节相关的新型生物活性肽。

• 批准号: 15590989
• 负责人: MIYAZATO Mikiya
• 金额: $ 2.24万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590989/
• 关键词: feeding behavior; orphan receptor; neuromedin S; neuromedin U; circadian rhythm; ghrelin; 摂食調節; エネルギー代謝; ペプチド

In this study, we found a novel agonist activity for neuromedin U type 2 receptor(NMU2R) in rat brain extract. This activity was eluted in fractions with a larger molecular mass by gel filtration compared to rat NMU. As a result of purification and structural determination, a novel 36-residue peptide was identified and designated as neuromedin S(NMS), because it is specifically expressed in the suprachiasmatic nuclei(SCN) of the hypothalamus. The C-terminal amidated seven-residue sequence of NMS is identical to that of NMU. Pharmacological characterization indicated that NMS and NMU share quite similar potency and efficacy for both NMU1R and NMU2R. In rat brain, NMS mRNA was specifically expressed in the SCN, which is the site of the master circadian pacemaker. NMS expression in the SCN showed a diurnal peak under light/dark cycling, but remained stable under constant darkness. Intracerebroventricular(ICV) administration of NMS in rats induced nonphotic type phase shifts in the circadi … More an rhythm of locomotor activity. On the other hand, low level expression of NMS mRNA was also found in the paraventricular nuclei of the hypothalamus, which is closely implicated in the regulation of the feeding. ICV-administered NMS induced more potent suppression of feeding than NMU. These findings suggest that NMS is implicated in the regulation of circadian rhythm and feeding behaviour(1).NMU is a potent endogenous anorectic and catabolic signaling molecule in manmalian, Following our recent observations of inactivity and slowed movement in neuromedin U knockout(NMU KO) mice, we compared nociceptive reflexes and environmental adaptation in NMU KO and wild-type mice. The results suggest that endogenous NMU may be involved in reflexes and adaptation to environmental stimuli (2). We also elucidated the central role of NMU in avian species using Japanese quail. Endogenous NMU plays an important role in the regulation of food intake and body temperature in avian species as well as mammalian (3).Ghrelin, a novel peptide purified from stomach in our laboratory, and cholecystokinin(CCK) are gastrointestinal hormones regulating feeding via the vagal afferent nerve. We examined the functional relationship between ghrelin and CCK in the short-term regulation of food intake using rats disrupted CCK type A receptor and electrophysiological study. The results indicate that the vagus nerve plays a crucial role in determining peripheral energy balance. The efficiency of ghrelin and CCK signal transduction may depend on the balance of their respective plasma concentration and/or on interactions between GHS-R and CCK-AR (4). Less

在这项研究中，我们发现了一种新的激动剂活性的神经介肽U 2型受体（NMU 2 R）在大鼠脑提取物。与大鼠NMU相比，通过凝胶过滤将该活性洗脱在具有更大分子量的级分中。作为纯化和结构测定的结果，鉴定了一种新的36个残基的肽，并将其命名为神经介肽S（NMS），因为它特异性地表达于下丘脑的视交叉上核（SCN）。NMS的C-末端酰胺化的七个残基序列与NMU的相同。药理学表征表明，NMS和NMU对NMU 1 R和NMU 2 R具有非常相似的效力和功效。在大鼠脑中，NMS mRNA特异性表达于SCN，这是主昼夜节律起搏器的位点。SCN中NMS的表达在光/暗循环下表现出昼夜高峰，但在恒定黑暗下保持稳定。侧脑室注射NMS可引起大鼠脑电节律的非光型相移， ...更多信息 运动活动的节奏另一方面，在下丘脑室旁核也发现了低水平的NMS mRNA表达，这与摄食的调节密切相关。ICV管理NMS诱导更有力的抑制比NMU的喂养。这些发现表明NMS涉及昼夜节律和进食行为的调节（1）JMU是哺乳动物中有效的内源性厌食和分解代谢信号分子。根据我们最近在神经介肽U敲除（NMU KO）小鼠中观察到的不活动和运动减慢，我们比较了NMU KO和野生型小鼠中的伤害性反射和环境适应。结果表明，内源性NMU可能参与对环境刺激的反射和适应（2）。我们还阐明了NMU在鸟类中的核心作用，使用日本鹌鹑。内源性NMU在鸟类和哺乳动物的摄食和体温调节中起着重要作用（3）。Ghrelin是本实验室从胃中纯化的一种新肽，CCK是通过迷走神经传入神经调节摄食的胃肠激素。本研究采用CCK A型受体阻断和电生理方法，探讨了Ghrelin和CCK在大鼠摄食短期调节中的功能关系。结果表明，迷走神经在决定外周能量平衡中起着至关重要的作用。Ghrelin和CCK信号转导的效率可能取决于其各自血浆浓度的平衡和/或GHS-R和CCK-AR之间的相互作用（4）。少

项目成果

Endogenous neuromedin U has anorectic effects in the Japanese quail.

• DOI: 10.1016/j.ygcen.2004.11.002
• 发表时间: 2005-02
• 期刊: General and comparative endocrinology
• 影响因子: 2.7
• 作者: S. Shousha;K. Nakahara;M. Miyazato;K. Kangawa;N. Murakami

Different effects of peripheral and central ghrelin on regulation of food intake.

外周和中枢饥饿素对食物摄入调节的不同作用。

• 发表时间: 2005
• 期刊: Gen.Comp.Endocrinol. 141
• 作者: Saad Shousha;et al.
• 通讯作者: et al.

Different effects of peripheral and central ghrelin on regulation of food intake in the Japanese quail

• DOI: 10.1016/j.ygcen.2004.12.021
• 发表时间: 2005-04-01
• 期刊: GENERAL AND COMPARATIVE ENDOCRINOLOGY
• 影响因子: 2.7
• 作者: Shousha, S;Nakahara, K;Murakami, N
• 通讯作者: Murakami, N

Neuromedin U is involved in nociceptive reflexes and adaptation to environmental stimuli in mice.

• DOI: 10.1016/j.bbrc.2004.08.136
• 发表时间: 2004-10
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: K. Nakahara;M. Kojima;R. Hanada;Yutaka Egi;T. Ida;M. Miyazato;K. Kangawa;N. Murakami

Neuromedin U is involved in nociceptive reflexes and adaptation to enviromental stimuli in mice.

Neuromedin U 参与小鼠的伤害性反射和对环境刺激的适应。

• 发表时间: 2004
• 期刊: Biochem.Biophys.Res.Commun. 323
• 作者: Keiko Nakahara;et al.
• 通讯作者: et al.