Translational Research on Adrenomedullin

• Project/Area Number: 18390236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: University of Miyazaki
• Principal Investigator: KITA Toshihiro (2007-2008) University of Miyazaki, 医学系研究科, 助教 (70315365); 江藤 胤尚 (2006) 宮崎大学, 理事 (10038854)
• Co-Investigator(Kenkyū-buntansha): KATO Johji 宮崎大学, 大学院・医学系研究科, 教授 (20274780) ; KITAMURA Kazuo 宮崎大学, 大学院・医学系研究科, 教授 (50204912) ; 永田 さやか 宮崎大学, 医学部, 研究員 (00452920) ; 北 俊弘 宮崎大学, 医学部, 助手 (70315365)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,300,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥3,000,000); Fiscal Year 2008: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
• 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 / 展開医療 / 抗炎症作用 / 関節リウマチ / TNF-α / CGRP / 片頭痛 / AM受容体 / 脳梗塞 / 治療応用 / 併用効果 / 高血圧 / 急性心筋梗塞 / 血管線維化抑制 / 腹部大動脈瘤 / 高血圧発症 / 糸球体腎炎抑制

Research Abstract

アドレノメデュリン(AM)は、ヒト褐色細胞腫(副腎髄質の腫瘍)の組織中より発見された生理活性ペプチドである。これまでの研究により、AMは正常な様々なヒトの臓器や組織で産生されており、心血管保護作用やその他の多彩な臓器保護作用を発揮することが判明した。本研究では、AMの好ましい作用を疾患の治療に応用すべく、基礎研究から臨床研究まで幅広く展開した。その結果、治療薬としての有用性が明確になり、一方で、AMの疾患における新たな役割や疾患治療薬としての新たな可能性も明かになった

Research Products

• [Journal Article] Effect of adrenomedullin on the cerebral circulation : relevance to primary headache disorders (2009)
  • Author(s): Petersen KA, Birk S, Kitamura K, Olesen J
  • Journal Title: Cephalalgia 29 Pages: 23-30
  • Peer Reviewed
• [Journal Article] Effects of uroguanylin on natriuresis in experimental nephroticrats (2009)
  • Author(s): Baba A, Fujimoto S, Kikuchi M, Kita T, Kitamura K
  • Journal Title: Nephrology 14 Pages: 80-85
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] A population-based, cross-sectional study of a Japanese community (2009)
  • Author(s): Nomura I, Kato J, Kitamura K : Association between body mass index and chronic kidney disease
  • Journal Title: Vasc Health Risk Manag 5 Pages: 315-320
  • Peer Reviewed
• [Journal Article] Effect of adrenomedullin on the cerebral circulation : relevance to primary headache disorders. (2009)
  • Author(s): Petersen KA, Birk S, et al.
  • Journal Title: Cephalalgia 29 Pages: 23-30
  • Peer Reviewed
• [Journal Article] Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits (2008)
  • Author(s): Okura T, Marutsuka K, Hamada H, Sekimoto T, Fukushima T, Asada Y, Kitamura K, Chosa E
  • Journal Title: Arthritis Res Ther 10
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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, NakamuraK, Nakamura-Uchiyama F, Matsushima Y, Imamura T, OnitsukaT, Asada Y, Nawa Y, Eto T, KitamuraK
  • Journal Title: Circ Res 102 Pages: 1368-1377
  • Peer Reviewed
• [Journal Article] Adrenomedullin 2/intermedin-like immunoreactivity in the hypothalamus and brainstem of rats (2008)
  • Author(s): Hashimoto H, Kitamura K, KawasakiM, Saito T, Suzuki H, Otsubo H, Ohbuchi T, Yokoyama T, Fujihara H, Takei Y, Ueta Y
  • Journal Title: Auton Neurosci 139 Pages: 46-54
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits. (2008)
  • Author(s): Okura T, Marutsuka K, et al.
  • Journal Title: Arthritis Res Ther 10
  • Peer Reviewed
• [Journal Article] Adrenomedullin 2/intermedin-like immunoreactivity in the hypothalamus and brainstem of rats. (2008)
  • Author(s): Hashimoto H, Kitamura K, et. al.
  • Journal Title: Auton Neurosci 139(1-2) Pages: 46-54
• [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
  • 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, et. al.
  • Journal Title: Vasc Health Risk Manag 3 Pages: 417-423
• [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
• [Journal Article] Adrenomedullin in mast cells of abdominal aortic aneurysm (2006)
  • Author(s): Tsuruda T, Kato J, Hatakeyama K,Yamashita A, Nakamura K, ImamuraT, Kitamura K, Onitsuka T, Asada Y, Eto T
  • Journal Title: Cardiovasc Res 70 Pages: 158-164
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of calcitonin gene-related peptide andadrenomedullin receptor (2006)
  • Author(s): Kuwasako K, Cao YN, Chu CP, Iwatsubo S, Eto T, Kitamura K
  • Journal Title: J Biol Chem 281 Pages: 7205-7213
  • Peer Reviewed
• [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, Sato Y, Hara S, Kitamura K, Eto T
  • Journal Title: Nephron Exp Nephrol 104
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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 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
• [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] 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)
• [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
• [Presentation] Beneficial effects of adrenomedullin and related peptide (2007)
  • Author(s): Kitamura K
  • Organizer: Sixth International Symposia on the CGRP family: CGRP, Adrenomedullin, Amylin, Intermedin and Calcitonin.
  • Place of Presentation: San Diego, 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