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Systematic survery for biologically active peptides in the atrium and pheochromocytoma tissue.

Research Project

Project/Area Number 15390251
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Miyazaki (2004-2005)
宮崎医科大学 (2003)

Principal Investigator

KITAMURA Kazuo  University of Miyazaki, 1st Dept Intern Med, Professor, 医学部, 教授 (50204912)

Co-Investigator(Kenkyū-buntansha) KATO Johji  University of Miyazaki, 1st Dept Intern Med, Research Associate, 医学部, 助手 (20274780)
KUWASAKO Kenji  University of Miyazaki, 1st Dept Intern Med, Research Associate, 医学部, 特任助手 (20381098)
ETO Tanenao  University of Miyazaki, Executive Director, 理事 (10038854)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsadrenomedullin / PAMP / biologically active peptide / redioimmunoassay / pheochromocytoma / atrium / amidicin / CGRP / 新規生理活性ペプチド / ウシ副腎髄質 / 血管作動性物質 / アミド化 / amidicin / 循環調節ペプチド / cAMP / ペプチド精製 / 副腎髄質 / C末アミド構造
Research Abstract

We discovered adrenomedullin (AM) in 1993 and found another hypetensive peptide proadrenomedullin N-terminal 20 peptide (PAMP) which is produced from adrenomedullin precursor. We have clarified that AM is a new cardiovascular hormone to regulate circulation and body fluid homeostasis. Further, AM shows protective actions for the heart and blood vessels in vitro and in vivo, suggesting that AM may be a new drugs for cardiovascular and inflammatory diseases. Thus, it is important to discover the new hormone and to study its function. We have concurrently advanced the another project to discover still unidentified vasoactive peptide in the porcine atrium and human pheochromocytoma tissue.
AM was discovered monitoring the activity that elevate cAMP in the rat platelet. We have searched biological active peptide using the cAMP elevation in cultured cells from pheochromocytoma. Using this assay, we isolated several peptides from pheochromocytoma tissue. These peptide were found to be VIP, PAC … More AP, CGRP and PHM. These peptides were known peptides, but we have isolated novel peptide which exist in the the pheochromocytoma. Many biologically active peptides has C-terminal amide structure which is essential for biological activity. We have established a novel method to detect a peptide with C-terminal amide structure. Using this method, we have isolated a novel 14 amino acids peptide in the atrium whose C-terminus was amidated. This peptide was termed amidicin. Amidicin is widely distributed in porcine tissue and is especially abundant in pituitary gland, cardiac ventricle and spleen. We have developed radioimmunoassay for human amidicin, and examined the distribution of amidicin in human tissue. We found that human amidicin is abundant in human pheochromocytoma tissue. We purified human amidicin from pheochromocytoma and determined its structure. Furthermore, amidicin was found to circulate in human blood in a considerable concentration. Amidicin may be a possible new peptide participating in circulation control. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (40 results)

All 2006 2005 2004 2003 Other

All Journal Article (30 results) Book (2 results) Patent(Industrial Property Rights) (2 results) Publications (6 results)

  • [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 (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of CGRP and adrenomedullin receptors.2006

    • Author(s)
      Kuwasako, K., Cao, Y.N., Chu, C.P., Iwatsubo, S., Eto, T., Kitamura, K.
    • Journal Title

      J Biol Chem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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, 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

      Arterioscler Thromb Vasc Biol 25

      Pages: 2480-2487

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Adrenomedullin : a protective factor for blood vessels.2005

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

      Arterioscler Thromb Vasc Biol. 25

      Pages: 2480-2487

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of adrenomedullin administration on acetic acid-induced colitis in rats.2005

    • Author(s)
      Ashizuka, S., Ishikawa, N., Kato, J., Yamaga, J., Inatsu, H., Eto, T., Kitamura, K.
    • Journal Title

      Peptides. 26

      Pages: 2610-2615

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Beyond vasodilation the antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta.2005

    • Author(s)
      Cao, Y.N., Kuwasako, K., Kato, J., Yanagita, T., Tsuruda, T., Kawano, J., Nagoshi, Y, Chen, A.F., Wada, A., Suganuma, T., Eto, T., Kitamura, K.
    • Journal Title

      Biochem Biophys Res Commun. 332

      Pages: 866-872

    • NAID

      40015392241

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antifibrotic effect of adrenomedullin on coronary adventitia in angiotensin II-induced hypertensive rats.2005

    • Author(s)
      Tsuruda, T., Kato, J., Hatakeyama, K., Masuyama, H., Cao, Y.N., Imamura, T., Kitamura, K., Asada, Y., Eto, T.
    • Journal Title

      Cardiovasc Res. 65

      Pages: 921-929

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adrenomedullin alleviates not only neointimal formation but also perivascular hyperplasia following arterial injury in rats.2005

    • Author(s)
      Tsuruda, T., Kato, J., Matsui, E., Hatakeyama, K., Masuyama, H., Imamura, T., Kitamura, K., Asada, Y., Eto, T.
    • Journal Title

      Eur J Pharmacol. 508

      Pages: 201-204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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] Adrenomedullin alleviates not only neointimal formation but also perivascular hyperplasia following arterial injury in rats.2005

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

      Eur J Pharmacol 508

      Pages: 201-204

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anti-Fibrotic Effect of Adrenomedullin on Coronary Adventitia in Angiotensin II-induced Hypertensive Rats.2005

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

      Cardiovasc Res 65・4

      Pages: 921-929

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adrenomedullin Alleviates Not Only Neointimal Formation But Also Perivascular Hyperplasia Following Arterial Injury In Rats.2005

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

      Eur J Pharmacol 508・1 3

      Pages: 201-204

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats.2004

    • Author(s)
      Nakamura, R., Kato, J., et al.
    • Journal Title

      Circulation 110

      Pages: 426-431

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats.2004

    • Author(s)
      Nakamura, R., Kato, J., Kitamura, K., Onitsuka, H., Imamura, T., Cao, Y., Marutsuka, K., Asada, Y, Kangawa, K., Eto, T.
    • Journal Title

      Circulation. 110

      Pages: 426-431

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of C-reactive protein on atherogenic mediators and adrenomedullin in human coronary artery endothelial and smooth muscle cells.2004

    • Author(s)
      Nagoshi, Y., Kuwasako, K., Cao, Y.N., Kitamura, K., Eto, T.
    • Journal Title

      Biochem Biophys Res Commun. 314

      Pages: 1057-1063

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins.2004

    • Author(s)
      Kuwasako, K., Cao, Y.N., Nagoshi, Y., Tsuruda, T, Kitamura, K., Eto, T.
    • Journal Title

      Mol Pharmacol. 65

      Pages: 207-213

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adrenomedullin induces matrix metalloproteinase-2 activity in rat aortic adventitial fibroblasts.2004

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

      Biochem Biophys Res Commun 325・1

      Pages: 80-84

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adrenomedullin receptors : pharmacological features and possible pathophysiological roles.2004

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

      Peptides 25・11

      Pages: 2003-2012

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats.2004

    • Author(s)
      Nakamura R., et al.
    • Journal Title

      Circulation 110・4

      Pages: 426-431

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential gene expression of adrenomedullin receptors in pressure- and volume-overloaded heart--role of angiotensin II.2004

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

      Peptides 25・7

      Pages: 1107-1114

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat.2003

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

      Hypertension 42

      Pages: 369-372

    • NAID

      110002710091

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity.2003

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

      J Biol Chem 278

      Pages: 22623-22630

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat.2003

    • Author(s)
      Cao, Y.N., Kitamura, K., Kato, J., Kuwasako, K., Ito, K., Onitsuka, H., Nagoshi, Y., Uemura, T., Kita, T., Eto, T.
    • Journal Title

      Hypertension. 42

      Pages: 369-372

    • NAID

      110002710091

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Angiotensin II modulates gene expression of adrenomedullin receptor components in rat cardiomyocytes.2003

    • Author(s)
      Mishima, K., Kato, J., Kuwasako, K.,.Imamura, T., Kitamura, K., Eto, T.
    • Journal Title

      Life Sci. 73

      Pages: 1629-1635

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity.2003

    • Author(s)
      Kuwasako, K., Kitamura, K., Nagoshi, Y, Cao, Y.N., Eto, T.
    • Journal Title

      J Biol Chem. 278

      Pages: 22623-22630

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of production and, secretion of adrenomedullin in the cardiovascular system.2003

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

      Regul Pept. 112

      Pages: 61-69

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Adrenomedullin in Cardiovascualr Disease2005

    • Author(s)
      Kato, J., Eto, T.
    • Publisher
      Springer Science and Business Media, Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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)] 非細菌性の炎症性疾患の予防又は治療剤2005

    • Inventor(s)
      北村和雄ほか6名
    • Industrial Property Rights Holder
      国立大学法人 宮崎大学
    • Industrial Property Number
      2005-111889
    • Filing Date
      2005-04-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 非細菌性の炎症性疾患の予防又は治療剤

    • Inventor(s)
      北村和雄ほか6名
    • Industrial Property Rights Holder
      国立大学法人 宮崎大学
    • Industrial Property Number
      2005-111889
    • Related Report
      2005 Annual Research Report
  • [Publications] Kuwasako K., et al.: "Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins"Biochem Biophys Res Commun. 301. 460-464 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Cao YN, et al.: "Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat"Hypertension. 42. 369-372 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mishima K, et al.: "Angiotensin II modulates gene expression of adrenomedullin receptor components in rat cardiomyocytes"Life Sci. 73. 1629-1635 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Cao YN, et al.: "Glycine-extended adrenomedullin exerts vasodilator effect through amidation in the rat aorta"Regul Pept. 113. 109-114 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuwasako K, et al.: "Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity"J Biol Chem. 278. 22623-22630 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eto T, et al.: "Regulation of production and secretion of adrenomedullin in the cardiovascular system"Regul Pept. 112. 61-69 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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