1999 Fiscal Year Final Research Report Summary
The pathopysiological significance of the novel hypotensive peptide, Adrenomedullin (AM) and Proadrenomedullin N-terminal 20 Peptide (PAMP)
| Project/Area Number |
09470171
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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 |
ETO Tanenao Miyazaki Medical College, School of Medicine, Professor, 医学部, 教授 (10038854)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Johji Miyazaki Medical College, 1st Dept. Intern Med, Research Associate, 医学部, 助手 (20274780)
KITAMURA Kazuo Miyazaki Medical College, 1st Dept. Intern Med, Assistant Professor, 医学部, 講師 (50204912)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Adrenomedullin / PAMP / PAMP-12 / Amidation / Hypotensive peptide / Hypertension / heat failure / renal failure |
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| Research Abstract |
(1)Cardiovascular effects of AM:
Chronically infused AM has a potent hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na+ excretion at a plasma AM concentration within the physiological limit. However, chronically infused PAMP had no hypotensive effect in rats.
We have demonstrated that cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.
(2) Immunoreactive AM and PAMP in human plasma:
Significantly higher concentrations of adrenomedullin (AM) and PAMP were shown in the cardiovascular and renal diseases. We have demonstrated that most of the AM immunoreactivity in human plasma represents the glycine-extended AM (iAM), intermediate from, and that the concentration of mature AM (mAM) is much lower than that of iAM. Both the mAM and iAM levels in plasma were found to be elevated in
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patients with heart failure or renal failure at almost the constant ratio. The elevation of plasma AM and PAMP were closely related to severity of the diseases, suggesting not only the role of AM and PAMP acting against further deterioration of the diseases. Further, we have clarified that the vasculature of the lower extremities and the heart produce and secrete matue form of adrenomedullin (mAM) and that the lung is a clearance site of circulating mAM.
(3) Distribution and molecular form of PAMP:
The distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentration of ir-PAMP were observed in the adrenal medulla. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9-20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control. Less
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[Publications] Serino R, Ueta Y, Hara Y, Nomura M, Yamamoto Y, Shibuya I, Hattori Y, Kitamura K, Kangawa K, Russell J.A., Yamashita H.: "Centrally administered adrenomedullin increases plasma oxytocin level with induction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of the rat"Endcrinology. 140(5). 2334-2342 (1999)
Description
「研究成果報告書概要(欧文)」より
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