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Molecular mechanisms and organ protection of inverse agonism on angiotensin II receptor antagonist

Research Project

Project/Area Number 18590916
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionFukuoka University

Principal Investigator

MIURA Shinichiro  Fukuoka University, 医学部, 准教授 (20343709)

Co-Investigator(Kenkyū-buntansha) SAKU Keijiro  福岡大学, 医学部, 教授 (40183371)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsアンジオテンシンII1型受容体括抗薬 / インバースアゴニスト / 腎保護作用 / AT1受容体 / 分子メカニズム / AT1受容体ブロッカー / ARB / インバースアゴニズム / Dah1食塩感受性ラット / 腎障害 / カルボキシル基 / ヒドロキシル基 / イノシトールリン酸産生
Research Abstract

アンジオテンシンII(Ang II)1型(AT1)受容体括抗薬(ARB)のインバースアゴニスト作用には、ARBの化学構造の僅かな違いによるAT1受容体への結合部位の差異が重要であることがわかった。しかし、ARBの中でもインバースアゴニスト作用の強いものと弱いものがあり、さらに、強いものでもAT1受容体への結合部位が異なっていた。さらに、このインバースアゴニト作用は、腎保護作用に重要であることが示唆された。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (36 results)

All 2009 2008 2007 2006

All Journal Article (16 results) (of which Peer Reviewed: 8 results) Presentation (15 results) Book (5 results)

  • [Journal Article] Clinical and pharmacotherapeutic relevance of the double-chain domain of the angiotensin II type 1 receptor blocker olmesartan2009

    • Author(s)
      Kiya Y, Miura S, Fujino M, Imaizumi S, Karnik SS, Saku K.
    • Journal Title

      Clin Exp Hypertens (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and pharmacotherapeutic relevance of the double-chain domain of the angiotensin II type 1 receptor blocker olmesartan.2009

    • Author(s)
      Kiya Y, Miura S, Fujino M, Imaizumi S, Karnik SS, Saku K.
    • Journal Title

      Clin Exp Hypertens (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conformational switch of angiotensin II type 1 receptor underlying mechanical stress-induced activation2008

    • Author(s)
      Yasuda N, Miura S, Akazawa H, Tanaka T, Qin Y, Kiya Y, Imaizumi S, Fujino M, Ito K, Zou Y, Ge J, Fukuhara S, Kunimoto S, Mochizuki N, Fukuzaki K, Sato T, Nakaya H, Saku K, Komuro I.
    • Journal Title

      EMBO Rep. 9

      Pages: 179-186

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential bonding interactions of inverse agonists of angiotensin II type 1 receptor in stabilizing the inactive-state2008

    • Author(s)
      Mmra S, Kiya Y, Kanazawa T, Imaizumi S, Fujino M, Matsuo Y, Karnik SS, Saku K.
    • Journal Title

      Mol Endocrinol. 22

      Pages: 139-146

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential bonding interactions of inverse agonists of angiotensin II type 1 receptor in stabilizing the inactive-state.2008

    • Author(s)
      Miura S, Kiya Y, Kanazawa T, Imaizumi S, Fujino M, Matsuo Y, Karnik SS, Saku K.
    • Journal Title

      Mol Endocrinol. 22

      Pages: 139-146

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conformational switch of angiotensin II type 1 receptor underlying mechanical stress-induced activation.2008

    • Author(s)
      Yasuda N, Miura S, Akazawa H, Tanaka T, Qin Y, Kiya Y, Imaizumi S, Fujino M, Ito K, Zou Y, Ge J, Fukuhara S, Kunimoto S, Mochizuki N, Fukuzaki K, Sato T, Nakaya H, Saku K, Komuro I.
    • Journal Title

      EMBO Rep 9

      Pages: 179-186

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential bonding interactions of inverse agonists of angiotensin II type l receptor in stabilizing the inactive-state2008

    • Author(s)
      Miura S, Kiya Y, Kanazawa T, Imaizumi S, Fujino M, Matsuo Y, Karnik SS, Saku K.
    • Journal Title

      Mol Endocrinol 22

      Pages: 139-146

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 臨床上重要なARBに対する疑問を解決!インバースアゴニスト活性について教えてください2007

    • Author(s)
      三浦 伸一郎
    • Journal Title

      薬局 58

      Pages: 2583-2586

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 代謝とRAS-脂質代謝2007

    • Author(s)
      三浦 伸一郎、朔啓 二郎
    • Journal Title

      Angiotensin Research 4

      Pages: 207-212

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor2006

    • Author(s)
      Mmra S, Fujino M, Hanzawa H, Kiya Y, Imaizumi S, Matsuo Y, Tomita S, Uehara Y, Karnik SS, Yanagisawa H, Koike H, Komuro I, Saku K.
    • Journal Title

      J Biol Chem. 281

      Pages: 19228-19295

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanism underlying inverse agonist of angiotension II type 1 receptor.2006

    • Author(s)
      Miura S, Fujino M, Hanzawa H, Kiya Y, Imaizumi S, Matsuo Y, Tomita S, Uehara Y, Kamik SS, Yanagisawa H, Koike H, Komuro K
    • Journal Title

      J Biol Chem 281

      Pages: 19228-19295

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ARBを降圧薬の第一選択にしてもよいか?2006

    • Author(s)
      三浦伸一郎, 朔啓二郎
    • Journal Title

      治療 88

      Pages: 941-945

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 薬物療法 : ARB2006

    • Author(s)
      三浦伸一郎
    • Journal Title

      日本臨床 64(Sup6)

      Pages: 322-327

    • Related Report
      2006 Annual Research Report
  • [Journal Article] アンジオテンシンII1型受容体拮抗薬の効果はすべて同じであるか2006

    • Author(s)
      三浦伸一郎
    • Journal Title

      J Jpn Coll Angiol 46

      Pages: 655-659

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 大規模臨床試験に基く降圧薬の位置づけ。アンジオテンシン受容体拮抗薬2006

    • Author(s)
      三浦伸一郎
    • Journal Title

      循環器科 60

      Pages: 544-549

    • Related Report
      2006 Annual Research Report
  • [Journal Article] インバースアゴニスト2006

    • Author(s)
      三浦伸一郎
    • Journal Title

      Ptog Med 26

      Pages: 61-64

    • Related Report
      2006 Annual Research Report
  • [Presentation] イルベサルタンの薬理学的特徴と受容体認識メカニズム2008

    • Author(s)
      藤野正礼、三浦伸一郎、松尾佳野、木谷嘉博、朔啓二郎
    • Organizer
      第31回日本高血圧学会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] A small difference in a chemical structure of ARB induces the differential pharmacological effects2008

    • Author(s)
      Fujino M, Miura S, Kiya Y, Imaizumi S, Karnik SS, Saku K.
    • Organizer
      22nd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular mechanisms of the antagonistic action between the AT, and AT2 receptors2008

    • Author(s)
      Miura S, Matsuo Y, Fujino M, Uehara Y, Saku K.
    • Organizer
      22nd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2008 Final Research Report
  • [Presentation] Clinical and pharmacotherapeutic relevance underlying the inverse agonism of angiotensin II type 1 receptor blocker2008

    • Author(s)
      Miura S, Fujino M, Kiya Y, Matsuo Y, Imaizumi S, Karnik SS, Saku K.
    • Organizer
      22nd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular Basis of the Stabilization of Angiotensin II Type 1 Receptor by Valsartan2008

    • Author(s)
      Miura S, Kiya Y, Imaizumi S, Matsuo Y, Fujino M, Saku K.
    • Organizer
      The 57th Annual Scientific Session on American College of Cardiology
    • Place of Presentation
      Chicago, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular and Structural Basis for Mechanical Stress-induced Activation of AT1 Receptor2008

    • Author(s)
      Akazawa H, Miura S, Yasuda N, Qin Y, Tanaka T, Itoh K, Liao CH, Kudo Y, Saku K, Komuro I.
    • Organizer
      The 72th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Clinical and pharmacotherapeutic relevance underlying the inverse agonism of angiotensin II type 1 receptor blocker.2008

    • Author(s)
      Miura S, Fujino M, Kiya Y, Matsuo Y, Imaizumi S, Karnik SS, Saku K.
    • Organizer
      22^<nd> Scientific Meeting of the International Society of Hypertension.
    • Place of Presentation
      Berlin, Germany.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular Mechanisms of Inverse Agonist for Angiotensin II Type 1 Receptor2007

    • Author(s)
      Miura S, Saku K.
    • Organizer
      SYMPOSIUM 7, THE RENIN ANGIOTENSIN ALDOSTERONE SYSTEM AND HYPERTENSION, 6th Congress of the Asian-Pacific Society of Hypertension
    • Place of Presentation
      Beijing, China
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular Mechanism Of Inverse Agonism In Mechanical Stress-induced Activation Of Angiotensin II Type 1 Receptor2007

    • Author(s)
      Yasuda N, Akazawa H, Miura S, Qin Y, Ito K, Kudo Y, Liao CH, Saku K, Komuro I.
    • Organizer
      78th Scientific Sessions of the American Heart Association
    • Place of Presentation
      Orlando, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Structural and Molecular Basis for Mechanosensation by Angiotensin II Type 1 Receptor2007

    • Author(s)
      Yasuda N, Akazawa H, Miura S, Qin Y, Ito K, Kudo Y, Liao C, Zou Y, Saku K, Komuro I.
    • Organizer
      第30回日本高血圧学会
    • Place of Presentation
      沖縄
    • Related Report
      2008 Final Research Report
  • [Presentation] アンジオテンシンレセプターの構造よりみた機能2007

    • Author(s)
      三浦伸一郎、朔啓二郎
    • Organizer
      第30回日本高血圧学会、シンポジウム「レニン・アンジオテンシン・アルドステロン系の新しい展開」
    • Place of Presentation
      沖縄
    • Related Report
      2008 Final Research Report
  • [Presentation] ARBの新しい展開 : インバースアゴニスト vs. アンタゴニスト2007

    • Author(s)
      三浦伸一郎、朔啓二郎
    • Organizer
      第50回日本腎臓学会学術総会、ワークショップ1 「慢性腎障害とレニン・アンジオテンシン系」
    • Place of Presentation
      浜松
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular basis of the stabilization of angiotensin II type 1 receptor by valsartan2007

    • Author(s)
      Miura S, Kiya Y, Imaizumi S, Tomita S, Matsuo Y, Uehara Y, Saku K.
    • Organizer
      The 71 Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] レニン-アンジオテンシン系に新たな展開。 AT2受容体のATl受容体シグナルに対するアンタゴニステックな役割2006

    • Author(s)
      三浦伸一郎、朔啓二郎
    • Organizer
      第43回日本臨床生理学会、シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] New aspect of angiotensin receptor: Molecular mechanism and pharmacotherapeutic relevance of inverse agonist for angiotensin II type 1 receptor2006

    • Author(s)
      三浦伸一郎、朔啓二郎
    • Organizer
      第10回日本心不全学会、パネルディスカッション
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Book] Angiotensin Progress. Differential pharmacotherapeutic effects of angiotensin II type 1 receptor blockers2008

    • Author(s)
      Miura S, Fujino M, Karnik SS, Saku K.
    • Publisher
      Nova Science Publishers
    • Related Report
      2008 Final Research Report
  • [Book] Differential pharmacotherapeutic effects of angiotensin II type 1 receptor blockers.2008

    • Author(s)
      Miura S, Fujino M, Karnik SS, Saku K.
    • Publisher
      Nova Science Publishers.
    • Related Report
      2008 Annual Research Report
  • [Book] 第7章 治療10. ARB(オルメサルタン)、高血圧ナビゲーター第2版(分担)2007

    • Author(s)
      三浦伸一郎
    • Publisher
      メディカルレビュー
    • Related Report
      2008 Final Research Report
  • [Book] AT1受容体活性:選択的遮断作用と逆活性作用、Annual Review「腎臓2007」(分担)2007

    • Author(s)
      三浦伸一郎
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] The ARB(分担)アンジオテンシン受容体の構造と結合2006

    • Author(s)
      三浦伸一郎
    • Total Pages
      487
    • Publisher
      メディカルレヴュー社
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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