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

2008 Fiscal Year Final Research Report

• Project/Area Number: 18590916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Fukuoka 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
• 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

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。

Research Products

• [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 (in press)
  • 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
  • Peer Reviewed
• [Journal Article] Differential bonding interactions of inverse agonists of angiotensin II type 1 receptor in stabilizing the inactive-state (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor (2006)
  • 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
  • Peer Reviewed
• [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
  • Year and Date: 20081009-11
• [Presentation] A small difference in a chemical structure of ARB induces the differential pharmacological effects (2008)
  • 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
  • Year and Date: 20080614-19
• [Presentation] Molecular mechanisms of the antagonistic action between the AT, and AT2 receptors (2008)
  • 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
  • Year and Date: 20080614-19
• [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: 22nd Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20080614-19
• [Presentation] Molecular Basis of the Stabilization of Angiotensin II Type 1 Receptor by Valsartan (2008)
  • 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
  • Year and Date: 20080329-31
• [Presentation] Molecular and Structural Basis for Mechanical Stress-induced Activation of AT1 Receptor (2008)
  • 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
  • Year and Date: 20080328-30
• [Presentation] Molecular Mechanisms of Inverse Agonist for Angiotensin II Type 1 Receptor (2007)
  • 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
  • Year and Date: 20071116-19
• [Presentation] Molecular Mechanism Of Inverse Agonism In Mechanical Stress-induced Activation Of Angiotensin II Type 1 Receptor (2007)
  • 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
  • Year and Date: 20071104-07
• [Presentation] Structural and Molecular Basis for Mechanosensation by Angiotensin II Type 1 Receptor (2007)
  • 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
  • Year and Date: 20071025-27
• [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
  • Year and Date: 20071025-27
• [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
  • Year and Date: 20070525-27
• [Presentation] Molecular basis of the stabilization of angiotensin II type 1 receptor by valsartan (2007)
  • 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
  • Year and Date: 20070315-17
• [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
  • Year and Date: 20061109-19
• [Presentation] New aspect of angiotensin receptor: Molecular mechanism and pharmacotherapeutic relevance of inverse agonist for angiotensin II type 1 receptor (2006)
  • 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
  • Year and Date: 20061013-15
• [Book] Angiotensin Progress. Differential pharmacotherapeutic effects of angiotensin II type 1 receptor blockers (2008)
  • Author(s): Miura S, Fujino M, Karnik SS, Saku K.
  • Total Pages: 221-234
  • Publisher: Nova Science Publishers
• [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
  • Total Pages: 262-263
  • Publisher: メディカルレビュー
• [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
  • Total Pages: 268-274
  • Publisher: 中外医学社