| Project/Area Number |
16390212
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
NAKAZATO Masamitsu UNIVERSITY OF MIYAZAKI, FACULTY OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 教授 (10180267)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Hideki UNIVERSITY OF MIYAZAKI, FACULTY OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (10305097)
MURAKAMI Noboru UNIVERSITY OF MIYAZAKI, FACULTY OF AGRICULTURE, PROFESSOR, 農学部, 教授 (80150192)
KANGAWA Kenji NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE, DIRECTOR GENERAL, 所長 (00112417)
DATE Yukari UNIVERSITY OF MIYAZAKI, FACULTY OF MEDICINE, PROFESSOR, フロンティア科学実験センター, 教授 (70381100)
TOSHINAI Koji UNIVERSITY OF MIYAZAKI, FACULTY OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (80381101)
森 正明 武田薬品工業(株), 開拓研究所, リサーチマネージャー
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | novel peptides / feeding regulation / energy homeostasis / gastrointestinal endocrine cells / mass spectrometry / ghrelin / NERP / グレリン / 摂食・エネルギー代謝調節 / ペプチドの網羅的解析 / オーファン受容体 / Ca^<2+>イメージング装置 / 腫瘍細胞株 / 高感度RIA系 / 消化管ペプチド / 迷走神経求心路 / コレシストキニン / ペプチドYY / ニューロペプチドW |
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| Research Abstract |
Exhaustive analyses of cultured cells using Peptidome and peptidmics will identify a variety of peptide fragments derived from a precursor protein and will enable the assumption of physiologically active peptides based on genetic information on the precursor protein and the amino acid sequences of the newly identified peptide fragments. Actually, when cultured digestive tract cells were analyzed using these technologies, 250 peptide fragments were orderly identified. By using these fragments, prospectively significant peptides were synthesized to assess their bioactivities of the targeted cells. After binding to its receptor, a physiologically active peptide changes the levels of intracellular calcium, cyclic AMP, and cyclic GMP as well as the amount of arachidonic acid metabolite and intracellular pH values to convey information. Following the administration of candidate peptides to the above-mentioned digestive tract cells, we performed in vitro screening to identify physiologically
… More
active peptides involved in biological regulation using fluorescence cellular imaging analysis, which employed fluorescent staining and a CCD camera for analyzing overtime changes in membrane electric field and the intracellular signal transmission system; and thus we discovered novel peptides, NERP-1 and NERP-2, in humans and rats. Through genetic engineering, ethopharmacology, and the development of exhaustive analytical technique, we elucidated their physiological implication that both NERPs regulate energy metabolism, water/electrolyte homeostasis, and the autonomic nervous system. Moreover, we have established a high-through put cell-based assay system that enables assessment of the dynamics of the intracellular signal transmission system, which contributed to the identification of 4 kinds of novel neuropeptides. These peptides are undergoing functional analysis. We have started translational medicine aiming to apply the appetite and GH secretion stimulatory effects of gastric ghrelin to treatment for patients with chronic obstructive lung disorder and for those with lower respiratory tract infection. Ghrelin has been demonstrated to have energy anabolic property as well as to enhance cellular regeneration and prevent inflammation. Less
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