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The systematic survey for novel vasoactive peptides produced in the adrenal medulla.

Research Project

Project/Area Number 12470160
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionMiyazaki Medical College

Principal Investigator

KITAMURA Kazuo  Miyazaki Medical College, 1st Dept Intern Med, Lecturer, 医学部, 講師 (50204912)

Co-Investigator(Kenkyū-buntansha) ETO Tanenao  Miyazaki Medical College, 1st Dept Intern Med, Professor, 医学部, 教授 (10038854)
KATO Johji  Miyazaki Medical College, 1st Dept Intern Med, Research Associate, 医学部, 助手 (20274780)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥7,500,000 (Direct Cost: ¥7,500,000)
Keywordsadrenomedullin / PAMP / adrenomedullin (11-26) / hypertensive peptide / Bovine adrenal medulla / radioimmunoassay / amidicin / C-terminal amide / PAMP / 新規生理活性ペプチド / アミド化 / 生理活性ペプチド / 副腎髄質 / 褐色細胞腫 / 降圧ペプチド / ANP / BNP / CNP / 血小板cAMP増加作用
Research Abstract

Mammalian circulation is regulated by subtle mechanisms involving several neural and hormonal factors. Several vasoactive peptides including angiotensin, ANP and endothelin are important regulators in the cardiovascular system. For clarifying the intricacies of circulation control, it is important to discover still unidentified vasoactive peptide.
We discovered adrenomedullin in 1993 and found another hypetensive peptide proadrenomedullin N-terminal 20 peptide (PAMP) which is produced from adrenomedullin precursor. In this study, we performed systematic survey for isopeptide of adrenomedullin and PAMP. Using the RIA for the ring structure of adrenomedullin, we isolated and determined adrenomedullin (11-26) as endogenous peptide. The synthetic adrenomedullin (11-26) produced dose-dependent strong pressor responses in unanesthetized rats in vivo.
Using a novel method to detect a peptide with C-terminal amide structure, we isolated a novel 14 amino acids peptide where 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. Amidicin may be a possible new peptide participating in circulation control.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Imai Y, et al.: "Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression"Arteriodcler Thromb Vasc Biol. 22. 1310-1315 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamada H., et al.: "Adrenomedullin stimulates the growth of cultured normal human osteoblasts as an sutocrine/paracine regulator"Peptides. 23. 2163-2168 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura R., et al.: "Beneficial effects of adrenomedullin on left ventricular remodeling after myocardial infarction in rats"Cardiovasc Res. 56. 373-380 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuchi H., et al.: "Cryofixation processing is an excellent method to improve the retention of adrenomedullin antigenicity"Histochem Cell Biol. 118. 259-265 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagoshi Y., et al.: "The calcitonin receptor-like receptor/receptor activity-modifying protein 1 heterodimer can function as a calcitonin gene-related peptide-(8-37)-sensitive adrenomedullin receptor"Eur J Pharmacol. 450. 237-243 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Cao, Y., Kitamura, K., Ito, K., Kato, J., Hashida, S., Morishita, K., and Eto, T.: "Glycine-extended adrenomedullin exerts vasodilator effect through amidation in the rat aorta."Regul. Pept.. 2918. 1-7 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, R., Kato, J., Kitamura, K., Onitsuka, H., Imamura, T., Marutsuka, K., Asada, Y., Kangawa, K. and Eto, T.: "Beneficial effects of adrenomedullin on left ventricular remodeling after myocardial infarction in rats."Cardiovasc. Res.. 56. 373-380 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagoshi, Y., Kuwasako, K., Ito, K., Uemura, T., Kato, J., Kitamura, K., and Eto, T.: "The calcitonin receptor-like receptor/receptor activity-modifying protein 1 heterodimer can function as a calcitonin gene-related peptide-(8-37)-sensitive adrenomedullin receptor."Eur. J. Pharmacol.. 450. 237-243 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuwasako, K., Kitamura, K., Onitsuka, H., Uemura, T., Nagoshi, Y., Kato, J., and Eto, T.: "Rat RAMP domains involved in adrenomedullin binding specificity."FEBS Lett.. 519. 113-116 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uemura, T., Kato, J., Kuwasako, K., Kitamura, K., Kangawa, K., and Eto, T.: "Aldosterone augments adrenomedullin production without stimulating pro-adrenomedullin N-terminal 20 peptide secretion in vascular smooth muscle cells."J. Hypertens.. 20. 1209-1214 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuchi, H., Suganuma, T., Sawaguchi, A., Ide, S., Kawano, J., Aoki, T., Kitamura, K., and Eto, T.: "Cryofixation processing is an excellent method to improve the retention of adrenomedullin antigenicity."Histochem. Cell. Biol.. 118. 259-265 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishiyama, Y., Kitamura, K., and Eto, T.: "Identification of a terminal amidicin : a novel peptide with C-terminal amide structure isolated from porcine cardiac atrium."Biochem. Biophys. Res. Commun.. 293. 741-746 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuruda, T., Kato, J., Kitamura, K., Mishima, K., Imamura T., Koiwaya, Y., Kangawa, K., and Eto, T.: "Roles of protein kinase C and Ca^<2+>-dependent signaling in angiotensin II-induced adrenomedullin production in rat cardiac myocytes."J. Hypertens.. 19. 757-763 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mishima, K., Kato, J., Kuwasako, K., Ito, K., Imamura, T., Kitamura, K., and Eto, T.: "Effects of endothelin on adrenomedullin secretion and expression of adrenomedullin receptors in rat cardiomyocytes."Biochem. Biophys. Res. Commun.. 287. 264-269 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuruda, T., Kato, J., Kitamura, K., Kuwasako, K., Imamura, T., Koiwaya, Y., Kangawa, K., and Eto, T.: "Secretion of proadrenomedullin N-terminal 20 peptide from cultured neonatal rat cardiac cells."Life Sci.. 69. 239-245 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitamura, K., Matsui, E., Kato, J., Kato, F., Kita, T., Tsuji, T., Kangawa, K., and Eto, T.: "Adrenomedullin (11-26) : a novel endogenous hypertensive peptide isolated from bovine adrenal medulla."Peptide. 22. 1713-1718 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuwasako, K., Kitamura, K., Ito, K., Uemura, T., Yanagita, Y., Kato, J., Sakata, T., and Eto, T.: "The seven amino acids of human RAMP2 (86-92) and RAMP3 (59-65) are critical for agonist binding to human adrenomedullin receptors."J. Biol. Chem.. 276. 49459-49465 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuruda, T., Kato, J., Kitamura, K., Imamura, T., Koiwaya Y., Kangawa, K., Komuro, I., Yazaki, Y., and Eto, T.: "Enhanced adrenomedullin production by mechanical stretching in cultured rat cardiomyocytes."Hypertension. 35. 1210-1214 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamakawa, H., Imamura, T., Matsuo, T., Onitsuka, H., Tsumori, Y., Kato, J., Kitamura, K., Koiwaya, Y., and Eto, T.: "Diastolic wall stress and ANG II cardiac hypertrophy and gene expression induced by volume overload."Am. J. Physiol.. 279. H2939-H2946 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirano, S., Imamura, T., Matsuo, T., Ishiyama, Y., Kato, J., Kitamura, K., Koiwaya, Y., and Eto, T.: "Differential responses of circulating and tissue adrenomedullin and gene expression to volume overload."J. Card. Fail.. 6. 120-129 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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
      2002 Annual Research Report
  • [Publications] Hamada H., et al.: "Adrenomedullin stimulates the growth of cultured normal human osteoblasts as an autocrine/paracine regulator"Peptides. 23. 2163-2168 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato I., et al.: "Plasma levels of adrenomedullin and atrial and brain natriuretic peptides in the general population : their relations to age and pulse pressure"Hypertens Res. 25. 887-892 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura R., et al.: "Beneficial effects of adrenomedullin on left ventricular remodeling after myocardial infarction in rats"Cardiovasc Res. 56. 373-380 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuchi H., et al.: "Cryofixation processing is an excellent method to improve the retention of adrenomedullin antigenicity"Histochem Cell Biol. 118. 259-265 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagoshi Y., et al.: "The calcitonin receptor-like receptor/receptor activity-modifying protein 1 heterodimer can function as a calcitonin gene-related peptide-(8-37)-sensitive adenomedullin receptor"Eur J Pharmacol. 450. 237-243 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitamura K., et al.: "Adrenomedullin(11-26) : a novel endogenous hypertensive peptide isolated from bovine adrenal medulla"Peptides. 22. 1713-1718 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsui E., et al.: "Biosynthesis and secretion of adrenomedullin and proadrenomedullin N-terminal 20 peptide in a rat model of endotoxin shock"Hypertens Res. 24. 543-549 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuwasako K., et al.: "The seven amino acids of human RAMP2(86) and RAMP3(59) are critical for agonist binding to human adrenomedullin receptors"J Biol Chem. 276. 49459-49465 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Eto T., et al.: "Adrenomedullin and its role in renal diseases"Nephron. 89. 121-134 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimosawa T., et al.: "Adrenomedullin, and endogenous Peptide, counteracts cardiovascular damage"Circulation. 105. 106-111 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kiyomizu A., et al.: "Distribution and molecular forms of adrenomedullin and proadrenomedulin N-terminal 20 peptide in the porcine gastrointestinal tract"J Gastroenterol. 36. 18-23 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北村和雄: "別冊・医学のあゆみ 循環器疾患-state of arts ver.2"医歯薬出版株式会社. 124-126 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kiyomizu A., et al.: "Distribution and molecular forms of adrenomedullin and proadrenomedullin N-terminal 20 peptide in the porcine gastrointestinal tract."J Gastroenterol.. 36. 18-23 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinoshita H., et al.: "Increased plasma levels of mature adrenomedullin in chronic glomerulonephritis."Nephron. 86. 333-338 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamakawa H., et al.: "Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload."Am J Physiol Heart Circ Physiol. 279. H2939-H2946 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirano S., et al.: "Differential responses of circulating and tissue adrenomedullin and gene expression to volume overload."J Card Fail. 6. 120-129 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuwasako K., et al.: "Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling."J Biol Chem. 275. 29602-29609 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsuruda T., et al.: "Enhanced adrenomedullin production by mechanical stretching in cultured rat cardiomyocytes."Hypertension. 35. 1210-1214 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北村和雄,江藤胤尚: "高血圧"日本臨床. 121-123 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北村和雄: "高血圧ナビゲーター"メディカルビュー社. 100-101 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2019-02-28  

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