Pharmacological Analysis and Therapeutic Application of Adrenomedullin and Adrenomedullin-related Peptide

• Project/Area Number: 18590819
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: University of Miyazaki
• Principal Investigator: KATO Johji University of Miyazaki, 医学系・研究科, 教授 (20274780)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,060,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥660,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: アドレノメデュリン / PAMP / 臓器保護作用 / 臨床治療学的応用 / カルシトニン受容体様受容体(CRLR) / 受容体活性調節蛋白(RAMP) / 降圧作用 / 併用効果 / 急性心筋梗塞 / 梗塞後リモデリング / ARB / 治療応用 / 血管線維化抑制 / 腹部大動脈瘤 / 肥満細胞 / 線維芽細胞 / 高血圧発症 / 降圧因子

Research Abstract

アドレノメデュリン(AM)とProadrenomedullin N-terminal 20 peptide(PAMP)は、同一の前駆体から産生されるが、相互に異なる作用を有する。本研究では、AMとPAMPの特徴的な作用を解析して、治療薬としての有用性の検討した。その結果、血管新生作用、心筋線維化抑制作用、併用降圧作用、大腸潰瘍治癒促進作用、血圧上昇抑制機能が明確になり、血管新生と大腸潰瘍治癒促進の作用機序についても解明された。また、大動脈疾患の発症進展の機序に関する新たな知見も得られた。本研究の結果を基盤として、AMとPAMPの臨床治療学的応用のための研究展開が可能である。

Research Products

• [Journal Article] Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy (2009)
  • Author(s): Ferrario CM, Varagic J, Habibi J, Nagata S, Kato J, Chappell MC, Trask AJ, Kitamura K, Whaley-Connell A, Sowers JR
  • Journal Title: Am J Physiol Heart Circ Physiol 296
• [Journal Article] Association between body mass index and chronic kidney disease : Apopulation-based, cross-sectional study of a Japanese community (2009)
  • Author(s): Nomura I, Kato J, Kitamura K
  • Journal Title: Vasc Health Risk Manag 5 Pages: 315-320
• [Journal Article] Functions of the extracellular histidine residues of receptor activity-modifying proteins vary within adrenomedullin receptors (2008)
  • Author(s): Kuwasako K, Kitamura K, Nagata S, Kato J
  • Journal Title: Biochem Biophys Res Commun 377 Pages: 109-113
• [Journal Article] Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm (2008)
  • Author(s): Tsuruda T, Kato J, Hatakeyama K, Kojima K, Yano M, Yano Y, Nakamura K, Nakamura-Uchiyama F, Matsushima Y, Imamura T, Onitsuka T, Asada Y, Nawa Y, Eto T, Kitamura K
  • Journal Title: Circ Res 102 Pages: 1368-1377
• [Journal Article] Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats (2008)
  • Author(s): Jessup JA, Trask AJ, Chappell MC, Nagata S, Kato J, Kitamura K, Ferrario CM
  • Journal Title: Am J Physiol Heart Circ Physiol 294
• [Journal Article] Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm (2008)
  • Author(s): Tsuruda T, Kato J, et al
  • Journal Title: Circ Res 102 Pages: 1368-1377
  • Peer Reviewed
• [Journal Article] Localization of the novel angiotensin peptide, angiotensin-(l-12), in heart and kidney of hypertensive and normotensive rats (2008)
  • Author(s): Jessup JA, Trask AJ, Chappell MC, Nagata S, Kato J, et al
  • Journal Title: Am J Physiol Heart Circ Physiol 294
  • Peer Reviewed
• [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, Sumi T, Mishima K, Masuyama H, Nakao H, Imamura T, Eto T, Kitamura K
  • Journal Title: Vasc Health Risk Manag 3 Pages: 417-423
• [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
  • Peer Reviewed
• [Journal Article] 循環器疾患とアドレノメデュリン (2007)
  • Author(s): 加藤丈司、北村和雄
  • Journal Title: ペプチドと創薬 Pages: 116-119
• [Journal Article] Adrenomedullin in mast cells of abdominal aortic aneurysm (2006)
  • Author(s): Tsuruda T, Kato J, Hatakeyama K, Yamashita A, Nakamura K, Imamura T, Kitamura K, Onitsuka T, Asada Y, Eto T
  • Journal Title: Cardiovasc Res 70 Pages: 158-164
• [Journal Article] Plasma adrenomedullin level and development of hypertension (2006)
  • Author(s): Kato J, Kitamura K, Eto T
  • Journal Title: J Hum Hypertens 20 Pages: 566-570
• [Journal Article] Isolation and identification of proangiotensin-12, a possible component of the renin-angiotensin system (2006)
  • Author(s): Nagata S, Kato J, Sasaki K, Minamino N, Eto T, Kitamura K
  • Journal Title: Biochem Biophys Res Commun 350 Pages: 1026-1031
• [Journal Article] Soluble guanylate cyclase stimulation on cardiovascular remodeling in angiotensin II-induced hypertensive rats (2006)
  • Author(s): Masuyama H, Tsuruda T, Kato J, Imamura T, Asada Y, Stasch JP, Kitamura K, Eto T
  • Journal Title: Hypertension 48 Pages: 972-978
• [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
• [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
• [Journal Article] Soluble guanylate cyclase stimulation of 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
• [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
• [Journal Article] Isolation and identification of proangiotensin-12,a possible component of the renin-angiotensin system. (2006)
  • Author(s): Nagata S, Kato J, Sasaki K, et al.
  • Journal Title: Biochem Biophys Res Commun 350(4) Pages: 1026-1031
• [Presentation] Importance of body weight control and commitment by physicians in controlling blood pressure: a community-based observational study. (2007)
  • Author(s): Kato J, Eto T, et. al.
  • Organizer: The 22nd Annual Scientific Meeting and Exposition of the American Society of Hypertension
  • Place of Presentation: Chicago, USA
• [Patent(Industrial Property Rights)] 非細菌性の炎症性疾患の予防又は治療剤 (2006)
  • Inventor(s): 北村和雄、稲津東彦、加藤丈司、石川直人、山家純一、江藤胤尚、芦塚伸也
  • Industrial Property Rights Holder: 国立大学法人宮崎大学
  • Industrial Property Number: 2005-111889
  • Filing Date: 2006-04-08
• [Patent(Industrial Property Rights)] 昇圧作用を有する新規ポリペプチド (2006)
  • Inventor(s): 北村和雄、加藤丈司、永田さやか
  • Industrial Property Rights Holder: 国立大学法人宮崎大学
  • Industrial Property Number: 2006-181709
  • Filing Date: 2006-06-30
• [Patent(Industrial Property Rights)] 動脈瘤の予防及び/又は治療薬 (2006)
  • Inventor(s): 鶴田敏博、北村和雄、加藤丈司、畠山金太
  • Industrial Property Rights Holder: 国立大学法人宮崎大学、キッセイ薬品工業株式会社
  • Industrial Property Number: 2006-193689
  • Filing Date: 2006-07-14