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

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390251
• 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 (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
• Keywords: adrenomedullin / PAMP / biologically active peptide / redioimmunoassay / pheochromocytoma / atrium / amidicin / CGRP

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 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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
• [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
• [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
• [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
• [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
• [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
• [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
  • Description: 「研究成果報告書概要(和文)」より
• [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
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
• [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
• [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
• [Book] Adrenomedullin in Cardiovascualr Disease (2005)
  • Author(s): Kato, J., Eto, T.
  • Total Pages: 131-154
  • Publisher: Springer Science and Business Media, Inc.
  • Description: 「研究成果報告書概要(和文)」より
• [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: 特許 特願2005-111889
  • Filing Date: 2005-04-08
  • Description: 「研究成果報告書概要(和文)」より