| Project/Area Number |
13854018
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Endocrinology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
KANGAWA Kenji National Cardiovascular Center Research Institute, Deputy Director, 副所長 (00112417)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Masayasu Kurume University, Institute of lifescience Molecuar Genetics, Professor, 分子生命科学研究所遺伝子情報研究部門, 教授 (20202062)
MIYAZATO Mikiya National Cardiovascular Center Research Institute, Head of Biochemistry, 生化学部, 室長 (50291183)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥123,240,000 (Direct Cost: ¥94,800,000、Indirect Cost: ¥28,440,000)
Fiscal Year 2005: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2004: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2003: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2002: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2001: ¥36,660,000 (Direct Cost: ¥28,200,000、Indirect Cost: ¥8,460,000)
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| Keywords | ophan GPCR ligand / ghrelin / neuromddin U / neuromddin S / appetite regulation / energy metabolism / cardiovascular system / circadian rhythm / NMU1R / NMU2R / INMU-KOマウス / 生活習慣病のモデルマウス / 視交叉上核 / 肝硬変モデルラット / 肝部分切除ラット / 肝機能改善効果 / 肝細胞増殖促進作用 / 増殖細胞核抗原(PCNA) / 肝細胞増殖因子(HGF) / 迷走神経系 / 成長ホルモン分泌促進作用 / 摂食促進作用 / グレリン産生細胞 / ラットの胎児期・新生児期 / 血漿グレリン濃度 / 新生ラットの体重増加 / 性発達に対する作用 / 接触促進作用 / 血管拡張作用 / 心不全ラット / 左室不全の改善 / cadiac cachexiaの改善 / 左室リモデリングの抑制 |
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| Research Abstract |
In this research project, we have analyzed the physiological functions of the novel ligands recently discovered by our group, and also searched for endogenous ligands of orphan GPCRs. We obteined fruitful results from this study as listed below.
1. Elucidation of physiological functions of ghrelin, a growth hormone (GH)- releasing and orexigenic peptide :
Ghrelin was discovered in the stomach as a GH-releasing peptide, and is known that it is mainly produced and secreted in the stomach, and has potent stimulating activities on GH release and appetite. In the present study, it is shown that ghrelin is also produced in the hypothalamus and peripheral tissues other than stomach, and has various central and peripheral regulatory roles in digestive tract, energy metabolism, cardiovascular system and regeneration of tissues. The research of ghrelin is now proceeding for clinical application. On the other hand, desacyl-ghrelin, lacking fatty acid modification of ghrelin and known to be an inactive form, is shown to have physiological function in cellular proliferation via unidentified receptor other than GHS-R.
2. Elucidation of physiological functions of Neuromedin U (NMU), an anorectic peptide :
In this study, novel functions of NMU are clarified such as anorectic activity, and the roles in stress response and metabolism. It should be noted that we have identified NMU as a novel regulatory factor of circadian rhythm.
3. Search for novel endogenous ligands by using assay systems of orphan receptor expressing cells :
In this study, we have succeeded in discovering a novel peptide, Neuromedin S (NMS), from rat brain. We also revealed very interesting facts that NMS, restrictedly expressed in suprachiasmatic nuclei (SCN) in the brain, has a role in regulating circadian rhythm by the mechanism different from NMU, and has more potent anorectic activity than NMU.
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