2006 Fiscal Year Final Research Report Summary
Functional analysis of a newly identified ligand and search for novel bioactive peptides associated with regulation of feeding behavior.
| Project/Area Number |
17590974
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
MIYAZATO Mikiya National Cardiovascular Center Research Institute, Director of Biochemistry, 生化学部, 部長 (50291183)
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| Co-Investigator(Kenkyū-buntansha) |
KANGAWA Kenji National Cardiovascular Center Research Institute, Deputy Director, 副所長 (00112417)
NAKAZATO Masamitsu Miyazaki University, Professor, 医学部, 教授 (10180267)
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| Project Period (FY) |
2005 – 2006
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| Keywords | peptide / orphan receptor / neuromedin S / neuromedin U / ghrelin |
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| Research Abstract |
Obesity is one of the most serious problems worldwide, because it is associated with lifestyle-related disease such as hypertension, cardiovascular disease and type 2 diabetes. The aims of this study are to identify novel bioactive peptides associated with regulation of energy balance and feeding behavior, and to clarify the biochemical and pathophysiological significance of the peptides.
In 2005, we identified a novel bioactive peptide, neuromedin S (NMS), in rat brain as an endogenous ligand for the G protein-coupled receptors (GPCRs) FM-3/GPR66 and FM-4/TGR-1. NMS has same core structure essential for receptor binding as anorexigenic neuropeptide, neuromedin U (NMU). Intracerebroventricular (ICV) administration of NMS in rats induced more potent suppression of feeding than that of NMU. α-MSH in the arcuate nucleus and CRH in the paraventricular nucleus were involved in NMS action on feeding. Furthermore we isolated NMS of Eurasian bombinid toads, indicating that NMS and NMU genes had already diverged at the level of the Amphibia.
Ghrelin, a novel peptide purified from stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is an acylated peptide that stimulates food intake. We showed that maternal ghrelin regulates fetal development during the late stages of pregnancy, ICV administration of des-acyl ghrelin to rats stimulates feeding through interactions with a receptor distinct from the GHS-R, and both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord.
In order to search for novel peptides associated with regulation of feeding behavior, we established twenty cell lines stably expressing orphan GPCRs, and developed new methods using BRET (Bioluminescence Resonance Energy Transfer) and receptor internalization.
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[Journal Article] Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor.2007
Author(s)
Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K, Nakazato M
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Journal Title
Endocrinology 147
Pages: 2306-2314
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Purification and characterization of feline ghrelin and its possible role.2007
Author(s)
Ida T, Miyazato M, Naganobu K, Nakahara K, Sato M, Lin XZ, Kaiya H, Doi K, Noda S, Kubo A, Murakami N, Kangawa K
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Journal Title
Domest Anim Endocrinol. 32
Pages: 93-105
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Maternal ghrelin plays an important role in rat fetal development during pregnancy.2006
Author(s)
Nakahara K, Nakagawa M, Baba Y, Sato M, Toshinai K, Date Y, Nakazato M, Kojima M, Miyazato M, Kaiya H, Hosoda H, Kangawa K, Murakami N
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Journal Title
Endocrinology 147
Pages: 1333-1342
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus.2006
Author(s)
Date Y, Shimbara T, Koda S, Toshinai K, Ida T, Murakami N, Miyazato M, Kokame K, Ishizuka Y, Ishida Y, Kageyama H, Shioda S, Kangawa K, Nakazato M
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Journal Title
Cell Metab. 4
Pages: 323-331
Description
「研究成果報告書概要(欧文)」より
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