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副腎髄質で産生される生理活性ペプチドの系統的探索

Research Project

Project/Area Number 17659285
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Endocrinology
Research InstitutionUniversity of Miyazaki

Principal Investigator

北村 和雄  University of Miyazaki, 医学部, 教授 (50204912)

Co-Investigator(Kenkyū-buntansha) 桑迫 健二  宮崎大学, フロンティア科学実験総合センター, 助教 (20381098)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsアドレノメデュリン / オーファン受容体 / 新規生理活性ペプチド / ラジオイムノアッセイ / ウシ副腎髄質 / 血管作動性物質 / アミド化 / amidicin / proangiotensin-12 / ラジオイムノアッセィ
Research Abstract

我々は1993年にヒト褐色細胞種組織より、アドレノメデュリンを強力な降圧作用を有する新規生理活性ペプチドとして発見した。我々はアドレノメデュリンの発見以降も、アドレノメデュリンの研究を推進すると同時に、さらなる新たな循環調節因子の探索を粘り強くすすめている。
アドレノメデュリンはラット血小板中のcAMPの増加活性を指標に発見できた。副腎髄質には未知の生理活性ペプチドが存在し、その多くのものが副腎髄質に作用している可能性がある。我々は副腎髄質由来の培養細胞のcAMP増加を指標にしたアッセイ法を確立し、新規生理活性ペプチドの探索をすすめ、すでにいくつかのペプチドを精製し、構造解析を決定した。その結果、これらのペプチドはVIP、 PHM、 CGRP、 PACAPであることが判明した。これらのペプチドはすべて降圧作用を有する生理活性ペプチドであった。
一方生理活性ペプチドの特徴の一つに、C末のアミド構造があげられる。我々は、ペプチドのC末がアミド化されていることを指標に、ペプチドの検索を行い、ブタ心房からamidicinを単離・構造決定した。amidicinは心臓、腎臓等の循環器組織の高濃度存在し、新たな循環調節因子としての可能性が示された。さらに、ヒトの褐色細胞腫にもamidicinが高濃度存在しちることを明らかにし、その精製と構造を決定した。さらに、ヒトamidicinのラジオイムノアッセイを確立し、血中にも循環していることを明らかにし、循環器疾患や腎不全患者では血中濃度が増加していることを明らかにした。

Report

(3 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2008 2007 2006 2005

All Journal Article (15 results) Presentation (1 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Adrenomedullin 2/intermedin-like immunoreactivity in the hypothalamurs and brainstem of rats.2008

    • Author(s)
      Hashimoto H, Kitamura K, et. al.
    • Journal Title

      Auton Neurosci 139(1-2)

      Pages: 46-54

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Combined use of brain natriuretic peptide and C-reactive protein for predicting cardiovascular risk in outpatients with type 2 diabetes mellitus.2007

    • Author(s)
      Tsuruda T, Kato J, et. al.
    • Journal Title

      Vasc Health Risk Manag 3

      Pages: 417-423

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Expression of interleukin-18 in coronary plaque obtained by atherectomy from patients with stable and unstable angina.2007

    • Author(s)
      Nishihira K, Imamura T, et. al.
    • Journal Title

      Thromb Res 121

      Pages: 275-279

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Plasma adrenomedullin level and development of hypertension.2006

    • Author(s)
      Kato J, Kitamura K, Eto T
    • Journal Title

      J Hum Hypertens 20(8)

      Pages: 566-570

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adrenomedullin in mast cells of abdominal aortic aneurysm.2006

    • Author(s)
      Tsuruda T, Kato J, Hatakeyama K, et al.
    • Journal Title

      Cardiovasc Res 70(1)

      Pages: 158-164

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Soluble guanylate cyclase stimulation on cardiovascular remodeling in angiotensin II-induced hypertensive rats.2006

    • Author(s)
      Masuyama H, Tsuruda T, Kato J, et al.
    • Journal Title

      Hypertension 48(5)

      Pages: 972-978

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Roles of adrenomedullin in hypertension and hypertensive organ damage.2006

    • Author(s)
      Kato J, Kitamura K, Eto T
    • Journal Title

      Curr Hypertens Rev 2(4)

      Pages: 283-295

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased production of adrenomedullin in glomeruli from anti-glomerular basement membrane glomerulonephritis rats treated with methylprednisolone.2006

    • Author(s)
      Iwatsubo S, Fujimoto S, Matsumoto M, et al.
    • Journal Title

      Nephron Exp Nephrol 104(1)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of calcitonin gene-related peptide and adrenomedullin receptors.2006

    • Author(s)
      Kuwasako K, Cao YN, Chu CP, et al.
    • Journal Title

      J Biol Chem 281(11)

      Pages: 7205-7213

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Functions of the Cytoplasmic Tails of the Human Receptor Activity-modifying Protein Components of Calcitonin Gene-related Peptide and Adrenomedullin Receptors.2006

    • Author(s)
      Kuwasako, K., Gao, Y.N., et al.
    • Journal Title

      J Biol Chem. 281

      Pages: 7205-7213

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adrenomedullin : a protective factor for blood vessels.2005

    • Author(s)
      Kato, J., Tsuruda, T.et al.
    • Journal Title

      Arterioscier Thromb Vasc Biol 25

      Pages: 2480-2487

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of adrenomedullin administration on acetic acid-induced colitis in rats.2005

    • Author(s)
      Ashizuka, S., Ishikawa, N., et al.
    • Journal Title

      Peptides 26

      Pages: 2610-2615

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Angiotensin II stimulates cardiac adrenomedullin production and causes accumulation of mature adrenomedullin independently of hemodynamic stress in vivo.2005

    • Author(s)
      Onitsuka, H., Imamura., et al.
    • Journal Title

      Horm Metab Res. 37

      Pages: 281-285

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Beyond vasodilation : the antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta.2005

    • Author(s)
      Cao, Y.N., Kuwasako, K., et al.
    • Journal Title

      Biochem Biophys Res Commun 332

      Pages: 866-872

    • NAID

      40015392241

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Antifibrotic effect of adrenomedullin on coronary adventitia in angiotensin II-induced hypertensive rats.2005

    • Author(s)
      Tsuruda, T., Kato, J., et al.
    • Journal Title

      Cardiovasc Res 65

      Pages: 921-929

    • Related Report
      2005 Annual Research Report
  • [Presentation] Beneficial effects of adrenomedullin and related peptide2007

    • Author(s)
      Kitamura K
    • Organizer
      Sixth International Symposia on the CGRP family: CGRP, Adrenomedullin, Amylin, Intermedin and Calcitonin.
    • Place of Presentation
      San Diego, USA
    • Related Report
      2007 Annual Research Report
  • [Book] 高血圧ナビゲーター 第2版2008

    • Author(s)
      北村 和雄
    • Total Pages
      2
    • Publisher
      メディカルビュー社
    • Related Report
      2007 Annual Research Report
  • [Book] Adrenomedullin in Cardiovascular Disease2005

    • Author(s)
      Kitamura, K., Kangawa, K., Eto, T.
    • Publisher
      Springer Science and Business Media, Inc.
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 心筋障害の予防又は治療剤2005

    • Inventor(s)
      北村 和雄ほか4名
    • Industrial Property Rights Holder
      国立大学法人 宮崎大学
    • Industrial Property Number
      2005-114786
    • Filing Date
      2005-04-12
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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