2002 Fiscal Year Final Research Report Summary
The systematic survey for novel vasoactive peptides produced in the adrenal medulla.
| Project/Area Number |
12470160
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
KITAMURA Kazuo Miyazaki Medical College, 1st Dept Intern Med, Lecturer, 医学部, 講師 (50204912)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Keywords | adrenomedullin / PAMP / adrenomedullin (11-26) / hypertensive peptide / Bovine adrenal medulla / radioimmunoassay / amidicin / C-terminal amide |
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| 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.
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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