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Studies on low molecular weight peptides regulating food intake after oral administration

Research Project

Project/Area Number 13460057
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 食品科学・栄養科学
Research InstitutionKyoto University

Principal Investigator

YOSHIKAWA Masaaki  Kyoto University, Graduate School of Agriculture, Professor, 農学研究科, 教授 (50026572)

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)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsCholecystokinin / ghrelin / neurotensin / histamine / enterostatin / bile acid / complement / prostaglandin / ナタネタンパク質 / napin / 血圧降下 / 動脈弛緩 / lorglumide / 摂食抑制 / GHS-R / 成長ホルモン分泌促進 / 摂食促進 / neurotensin / prostaglandin D_2 / 補体C5a / β-lactotensin / NT1レセプター / NT2レセプター / D2レセプター / enterostatin / 補体C3a
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.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All 2005 2004 2003 Other

All Journal Article (9 results) Publications (16 results)

  • [Journal Article] Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin.2005

    • Author(s)
      Akihiro, Asakawa
    • Journal Title

      Gut 54

      Pages: 18-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The anorectic effect of neurotensin is mediated via a histamine H1 receptor in mice.2004

    • Author(s)
      Kousaku, Ohinata
    • Journal Title

      Peptides 25

      Pages: 2135-2138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] EM574, a motilide, has an orexigenic activity with affinity for growth-hormone secretagogue receptor.2003

    • Author(s)
      Akihiro, Asakawa
    • Journal Title

      J. Gastroenterol. Hepatol 18

      Pages: 881-882

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Enterostatin (VPDPR) and its peptide fragment DPR reduce serum cholesterol levels after oral administration in mice.2003

    • Author(s)
      Yasuyuki, Takenaka
    • Journal Title

      Biosci. Biotechnol. Biochem 67

      Pages: 1620-1622

    • NAID

      110002694278

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] β-Lactotensin and neurotensin rapidly reduce serum cholesterol via NT2 receptor.2003

    • Author(s)
      Rena, Yamauchi
    • Journal Title

      Peptides 24

      Pages: 1955-1961

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] EM574, a motilide, has an orexigenic activity with affinity for growth-hormone secretagogue receptor.2003

    • Author(s)
      Akihiro, Asakawa
    • Journal Title

      J.Gastroenterol.Hepatol 18

      Pages: 881-882

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Enterostatin (VPDPR) and its peptide fragment DPR reduce serum cholesterol levels after oral administration in mice.2003

    • Author(s)
      Yasuyuki, Takenaka
    • Journal Title

      Biosci.Biotechnol.Biochem. 67

      Pages: 1620-1622

    • NAID

      110002694278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] [TrP^3, Arg^5]-ghrelin(1-5) stimulated growth hormone secretion and food intake via growth hormone secretagogur (GHS) receptor.

    • Author(s)
      Kousaku, Ohinata
    • Journal Title

      Peptides (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] [Trp^3, Arg^5]-ghrelin(1-5) stimulated growth hormone secretion and food intake via growth hormone secretagogur (GHS) receptor.

    • Author(s)
      Kousaku, Ohinata
    • Journal Title

      Peptides (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaaki.Yoshikawa: "Delta Opioid Peptides Derived from Plant Proteins"Current Pharmaceutical Design. 9・16. 1325-1330 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shuzhang. Yang: "Structure-activity relationship of rubiscolins as x Opioid peptides"Peptides. 24. 503-508 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ewa.D.Marczak: "New antihypertensive peptides isolated from rapeseed"Peptides. 24. 791-798 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kunihiko. Onishi: "Optimal designing of β-conglycinin to genetically Incorporate RPLKPW, a potent anti-hypertensive peptide"Peptides. 25. 37-43 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Rena.Yamauchi: "β-Lactotensin and neurotensin rapidly reduce serum cholesterol via NT_2 receptor"Peptides. 24. 1955-1961 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Andrzej.W.Lipkowski: "Is RNA-laden p24 capsid protein a vector for HIV?"Medical Hypotheses. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 吉川 正明: "タンパク質工学"医学出版. 306 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大日向耕作: "補体C3aとC5aは神経系にも作用する抗鎮痛・抗健忘や摂食調節作用が明らかに"化学と生物. 41・1. 7-8 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi R: "Characterization of β-lactotensin, a bioactive peptide derived from bovine β-lactoglobulin, as a neurotensin agonist"Biosci Biotechnol Biochem. 67・4. 940-943 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asakawa A: "EM574, a motilide, has an orexigenic activity with affinity for growth-hormone secretagogue receptor"J Gastro Hepato. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takenaka Y: "Anti-analgesic activity of enterostatin (VPDPR) is mediated by corticosterone"Peptides. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi R: "Antinociception induced by β-lactotensin, a neurotensin agonist peptide derived from β-lactoglobulin, is mediated by NT_2 and D_1 receptors"Life Sci. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Ohinata: "Albutensin A and complement C3a decrease food intake in mice"Peptides. 23. 127-133 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Ohinata: "Proadrenomedullin N-terminal 20 peptide (PAMP) inhibits food intake and gastric emptying in mice"Peptides. 22. 589-595 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Ohinata: "Novel actions of proadrenomedullin N-terminal 20 peptide (PAMP)"Peptides. 10. 1809-1816 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大日向 耕作: "ヒト血清アルブミン由来のalbutensin Aが摂食およびgastric emptyingに及ぼす影響"消化管ホルモン(XIX) 別冊. 7月号. 20-23 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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