2003 Fiscal Year Final Research Report Summary
Studies on low molecular weight peptides regulating food intake after oral administration
| Project/Area Number |
13460057
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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 |
食品科学・栄養科学
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| Research Institution | Kyoto University |
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Principal Investigator |
YOSHIKAWA Masaaki Kyoto University, Graduate School of Agriculture, Professor, 農学研究科, 教授 (50026572)
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| Co-Investigator(Kenkyū-buntansha) |
TAKENAKA Yasuyuki Kobe Shoin Women's College, Department of Life Science, Lecturer, 生活科学科, 講師 (20273518)
INUI Akio Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (80168418)
FUKUOKA Shinichi Kyoto University, Graduate School of Agriculture, Associate Professor, 農学研究科, 助教授 (20183923)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Cholecystokinin / ghrelin / neurotensin / histamine / enterostatin / bile acid / complement / prostaglandin |
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| Research Abstract |
Arg-lle-Tyr, which has been isolated as an inhibitor for angiotensin l-converting enzyme from subtilisin digest of rape seed protein suppressed food intake after oral administration in mice. The anorectic activity was blocked by lorglumide, an antagonist for CCK_1 receptor. However, Arg-lle-Tyr did not have affinity for CCK_1 receptor, suggesting that it stimulated release of cholecystokinin.
Ghrelin has been isolated as a growth hormone secretagogue. It has octanoyl Ser residues at the third position from the amino terminus, which is essential for the secretagogue activity. Inui et al. found that ghrelin has an orexigenic activity while desacyl ghrelin has an anorectic activity. We synthesized pentopeptide anologues at the amino terminus of ghrelin, in which octanoyl Ser residue is replaced with Trp residue. Among them, [Trp^3, Arg^5]-ghrelin (1-5) showed affinity for ghrelin receptor GHS-R (IC_50=10mM). It stimulated growth hormone release after oral administration, and food intake after intracerebroventriculdr administration.
We demonstrated that an anorectic activity of neurotensin is mediated by histamine release and H_1 receptor. We also found that neurotensin stimulated bile acid secretion and reduced serum cholesterol level after oral administration.
We found that enterostatin, an endogenous anorectic peptide, stimulated bile acid secretion and reduced serum cholesterol level after oral administration. Furthermore, it suppressed analgesic activity of morphin.
We found that an orexigenic activity of complement C5a is mediated by prostaglandin (PG) D_2 and DP-receptor. We also found that complement C3a has an anorectic activity which is mediated by PGE_2 and EP_4-receptor.
Thus, mode of action of some endogenous peptides regulating food intake have been clarified, and their new biological activities have been found.
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