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1998 Fiscal Year Final Research Report Summary

The study of the novel hypotensive peptide, Adrenomedullin (AM) and Proadrenomedullin N-terminal 20 Peptide (PAMP)

Research Project

Project/Area Number 08457213
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  宮崎医科大学, 医学部, 講師 (50204912)

Project Period (FY) 1996 – 1998
KeywordsAdrenomedullin / PAMP / PAMP-12 / Amidation / Hypotensive peptide / Hypertension / heart failure / renal failure
Research Abstract

(1) Immunoreactive AM 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 form, 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 patients with heart failure or renal failure at almost the constant ratio. The elevation of plasma AM was closely related to severity of the diseases, suggesting not only the role of AM acting against further deterioration of the diseases
(2) 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. In addition, chronically infused adrenomedullin had a hypotensive effect accompanied by sign … More ificant reductions of plasma renin activity and plasma aldosterone concentration in 2K-lC hypertensive and sham-operated 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.
(3) Distribution and molecular form of PAMP :
The distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations 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 of 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

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Tsuruda T, Kato J, Kitamura K, Kuwasako K, Imamura T, Koiwaya Y, Tsuji T, Kanagawa K. Eto T: "Adrenomedullin : a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes." Hypertension. 31(1Pt12). 505-510 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura K, Kato J, Kawamoto M, Tanaka M, Chino N, Kangawa K, Eto T: "The intermediate form of glycine-extended adrenomedullin in the major circulating molecular form in human plasma." Biochem Biophys Res Commun. 244(2). 551-555 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saita M, Shimokawa A, Kunitake T, Kato K, Hanamori T, Kitamura K, Eto T, Kannan H: "Central actions of adrenomedullin on cardiovascular parameters and sympathetic outflow in conscious rats." Am J Physiol. 274(4Pt2). R979-984 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirano S, Ishiyama Y, Matsuo T, Imamura T, Sakata J, Kitamura K, Koiwaya Y, Eto T: "Decrease in circulating and urine adrenomedullin concentrations in stroke-prone spontaneously hypertensive rats." Hypertens Res. 21(1). 23-28 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saita M, Ishizuka Y, Kato K, Kunitake T, Hanamori T, Kitamura K, Eto T, Kannan H: "Cardiovascular and sympathetic effects of proadrenomedullin NH2-terminal 20 peptide in conscious rats." Regul Pept. 77(1-3). 147-153 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kita T, Kitamura K, Kuwasako K, Kawamoto M, Eto T: "Short-term mondulation of the renin-angiotensin system does not alter plasma adrenomedullin concentration in humans." J Hypertens. 16(12Pt2). 2057-2062 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuo Kitamura, Kenji Kanagawa, Hisayuki Matsuo, Tanenao Eto: "Adrenomedullin" IOS Press, 27-36 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura K: "Aggiornamento II" Uses-firenze Press, 108-113 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura, K., Kato, J., Kawamoto, M., Tanaka, M., Chino, N., Kangawa, K.and Eto, T.: "Intermediate form of glycine-extended adrenomedullin is major circulating molecular from in human plasma." Biochem.Biophys.Res.Commun.244. 551-555 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuruda, T., Kato, J., Kitamura, K., Kuwasako, K., Imamura, T., Koiwaya, Y., Tsuji, T., Kanagawa, K.and Eto, T.: "Adrenomedullin : a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes." Hypertension. 31. 505-510 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsui, E., Kato, J., Kitamura, K., and Eto, T.: "Lack of hypotensive effect of chronically infused proadrenomedullin N-terminal 20 peptide in rats." Horm.Metab.Res.30. 555-556 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata, K., Kato, J., Kitamura, K., Kawamoto, M., Tanaka, N., Eto, T.and Takasaki, M.: "Dissociation of adrenomedullin concentrations between plasma and cerebrospinal fluid in pregnant and non-pregnant women" Eur.J.Endocrinol. 139. 611-614 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kita T,Kitamura K,Kuwasako K,Kawamoto M,Eto T.: "Short-term modulation of the renin-angiotensin system does not alter plasma adrenomedullin concentration in humans" J.Hypertens. 16 (12 Pt 2). 2057-62 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami Y,Hattori Y,Taniyama M,Kitamura K,Kasai K: "Adrenomedullin regulation by thyroid hormone in the rat" Life Sci.63(24). PL337-42 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saita M,Ishizuka Y,Kato K,Kunitake T,Hanamori T,Kitamura K,Eto T,Kannan H: "Cardiovascular and sympathetic effects proadrenomedullin NH2-terminal 20 peptide in conscious rats." Regul Pept.16 ; 77 (1-3). 147-53 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kikumoto k, Kudo A,Hayashi Y,Minamino N,Inoue S,Dohi K,Kitamura K,Kangawa K,Matsuo H,Furuya H: "Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage." Anesth Analg.87 (4). 859-63 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitani M,Sakata J,Asada Y,Kitamura K,Eto T: "Distribution and expression of adrenomebullin in human gastrointerstinal tissue." Ann Clin Biochem.35(5). 643-8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura T,Honda K,Ishikawa S,Kitamura K,Eto T,Saito T: "Plasma adrenomedullin levels in patients with non-insulin dependent diabetes mellitus : close relationships with diabetic complications." Endocr J.45 (2). 241-6 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuwasako K,Kida O,Kitamura K,Kato J,Eto T: "Plasma adrenomedullin in cerebrovascular disease : a possible indicator of endothelial injury." Int Angiol.16(4). 272-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirano S,Ishiyama Y,Matsuo T,Imamura T,Sakata J,Kitamura K,Koiwaya Y,Eto T: "Decrease in circulating and urine adrenomedullin concentrations in stroke-prone spontaneously hypertensive rats." Hypertens Res.21 (1). 23-8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kudo A,Iwano M,Minamino N,Sato H,Nishino T,Hirata E,Akai Y,Shiiki H,Kitamura K,Kangawa K,Matsuo H,Dohi K: "Measurement of plasma and urinary adrenomedullin in patients with IgA nephropathy" Nephron. 78 (4). 389-94 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saita M,Shimokawa A,Kunitake T,Kato K,Hanamori T,Kitamura K,Eto T,Kannan H: "Central actions of adrenomedullin on cardiovascular parameters and sympathetic outflow in conscious rats." Am J Physiol.274 (4 Pt 2). R979-84 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato, J., Kitamura, K., Matsui, E., Tanaka, M., Ishizaka, Y., Kita, T., Kanagawa, K.and Eto, T.: "Plasma adrenomedullin and natriuretic pepties in patients with essential or malignant hypertension." Hypertens.Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirayama, N., Kitamura, K., Imamura, T., Kato, J., Koiwaya, Y.and Eto, T.: "Molecular forms of circulating adrenomedullin in patients with congestive heart failure." J.Endocrinol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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