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Clinical application and elucidation of significance of natriuretic peptide family

Research Project

Project/Area Number 01480288
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionKyoto University

Principal Investigator

NAKAO Kazuwa  Kyoto Univ. Dept. of Med. Associate Professor, 医学部, 講師 (00172263)

Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1989: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsNatriuretic Peptide / ANP / BNP / CNP / Natriuretic Peptide Receptor / Endothelial Cell / Vascular Smooth Muscle Cells / Monoclonal Antibody / モノクロ-ナル抗体 / 心房性ナトリウム利尿ペプチド(ANP) / 脳性ナトリウム利尿ペプチド(BNP) / Cタイプナトリウム利尿ペプチド(CNP) / 心臓ホルモン / 神経ペプチド / CNP遺伝子 / ノ-ザンブロット解析 / 心房性ナトリウム利尿ペプチド / 脳性ナトリウム利尿ペプチド
Research Abstract

The natriuretic peptide system consists of, at least, three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and three receptors, ANP receptor-A (guanylate cyclase A), ANP receptor-B (guanylate cyclase B) and clearance receptor (C receptor).
ANP, the prototype of natriuretic peptides, is mainly produced in the atrium and secreted into the circulation as a cardiac hormone. ANP is also produced in the ventricle, and in the central nervous system. BNP first isolated from the porcine brain has a marked divergence in its molecular size and the sequence among species. In humans and rats, the major site of production of BNP is the ventricle of the heart. BNP is also secreted into the circulation as a cardiac hormone. The plasma BNP level in normal subjects is approximately one sixths of the plasma ANP level, however, the plasma BNP level markedly increases in heart failure, renal failure and hypertension and the augmentation of the BNP secretion is much larger than that of the ANP secretion. In addition, clearance of BNP from the circulation is slower than that of ANP. Furthermore, BNP is secreted more urgently than ANP in acute heart failure. CNP distributes mainly in the central nervous system and pituitary gland. No significant amount of CNP is detectable in the heart and plasma. Thus, CNP is a local regulator rather than a cardiac hormone.
Three natriuretic receptors have ligand selectivity. The rank order in potency for cyclic GMP production via ANP receptor-A is ANP>BNP>>CNP, while that via ANP-B receptor is CNP>ANP>BNP. The rank-order of binding affinity for C receptor is ANP>CNP>BNP.
The complicated natriuretic peptide system is implicated in the control of body fluid and blood pressure in endocrine and paracrine fashions.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] M.Mukoyama et al.: "Brain natriuretic peptide (BNP)as a novel cardiac hormone in humans-Evidence for an exquisite dual natriuretic peptide system,atrial natriuretic peptide and brain natriuretic peptide-" J.Clin.Invest.87. 1402-1412 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K.Hosoda et al.: "Expression of brain natriuretic peptide gene in human heart-Production in ventricle" Hypertension. 17. 1152-1156 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Ogawa et al.: "Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats-The ventricle is a major site of synthesis and secretion of brain natriuretic peptide" Circ.Res.69. 491-500 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Komatsu et al.: "C-type natriuretic peptide (CNP) in rats and humans" Endocrinology. 129. 1104-1106 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Yoshimura et al.: "Hemodynamic,renal,and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure" Circulation. 84. 1581-1588 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S.Suga et al.: "Receptor selectivity of natriuretic peptide family,atrial natriuretic peptide,brain natriuretic peptide and C-type natriuretic peptide" Endocrinoligy. 130. 229-239 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Mukoyama et al.: "Brain natriuretic peptide (BNP) as a novel cardiac hormone in humans - Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide -" J. Clin. Invest.87. 1402 - 1412 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Hosoda et al.: "Expression of brain natriuretic peptide gene in human heart - Production in ventricle" Hypertension. 17. 1152 - 1156 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Ogawa et al.: "Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats - The ventricle is a major site of synthesis and secretio of brain natriuretic peptide" Circ. Res.69. 491 - 500 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Komatsu et al.: "C-type natriuretic peptide (CNP) in rats and humans" Endocrinology. 129. 1104 - 1106 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Yoshimura et al.: "Hemodynamic, renal, and hurmonal responses to brain natriuretic peptide infusion in patients with congestive heart failure" Circulation. 84. 1581 - 1588 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Suga et al.: "Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide" Endocrinology. 130. 229 - 239 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Mukoyama et al.: "Brain natriuretic peptide(BNP)as a novel cardiac hormone in humansーEvidence for an exquisite dual natriuretic peptide aystem,atrial natriuretic peptide and brain natriuretic peptideー" J.Clin.Invest.87. 1402-1412 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Hosoda et al.: "Expression of brain natriuretic peptide gene in human heartーProduction in ventricle" Hypertension. 17. 1152-1156 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Ogawa et al.: "Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive ratsーThe ventricle is a major site of synthesis and secretion of brain natriuretic peptide" Circ.Res.69. 491-500 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Komatsu et al.: "Cーtype natriuretic peptide(CNP)in rats and humans" Endocrinology. 129. 1104-1106 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Yoshimura et al.: "Hemodynamic,renal,and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure" Circulation. 84. 1581-1588 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Suga et al.: "Receptor selectivity of natriuretic peptide family,atrial natriuretic peptide,brain natriuretic peptide and Cーtype natriuretic peptide" Endocrinology. 130. 229-239 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] G.Takemura,H.Fujiwara,H.Yoshida,M.Mukoyama,Y.Saito,K.Nakao,T.Fujiwara,T.Uegaito,H.Imura and C.Kawai.: "Identification and distribution of atrial natriuretic polypeptide in ventricular myocardium of humans with myocardial infarction." J.Pathology. 161. 285-292 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Mukoyama,K.Nakao,Y.Saito,Y.Ogawa,K.Hosoda,S.Suga,G.Shirakami,M.Jougasaki and H.Imura.: "Increased human brain natriuretic peptide in congestive heart failure." N.Engl.J.Med.323. 757-758 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Mukoyama,K.Nakao,Y.Saito,Y.Ogawa,K.Hosoda,S.Suga,G.Shirakami,M.Jougasaki,K.Obata,H.Yasue and H.Imura.: "Brain natriuretic peptide is a novel cardiac hormone secreted from the ventricle in humans." Proceedings of the XIth International Congress of Nephrology. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Fujiwara,H.Fujiwara,G.Takemura,M.Mukoyama,Y.Saito,K.Nakao,H.Imura,M.Nakano,K.Baba.: "Expression and distribution of atrial natriuretic polypeptide in the ventricles of children with myocarditis and/or myocardial infarction secondary to Kawasaki disease:Immunohistochemical study." Am.Heart J.120. 612-618 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Kambayashi,K.Nakao,H.Imura,T.Kawabata,M.Nakamura,K.Inouye,N.Yoshida and H.Imura.: "Biological characterization of human brain natriuretic peptide(BNP)and rat BNP:speciesーspecific actions of BNP." Biochem.Biophys.Res.Commun.173. 599-605 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K Obata,H.Yasue,K.Okumura,K.Matsuyama,H.Ogawa,M.Kurose,Y.Saito,K.Nakao H.Imra and M.Nobuyoshi.: "Atrial natriuretic polypeptide is removed by the lungs and released into the left atrium as well as the right atrium in humans." J.Am.Coll.Cardiol.15. 1537-1543 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Kambayashi.K.Nakao,M.Mukoyama,Y.Saito,Y.Ogawa,S.Shiono,K.Inouye,N.Yoshida and H.Imura.: "Isolation and sequence determination of human brain natriuretic peptide in human atrium." FEBS Lett.259. 341-345 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Nishimura,T.Ban,Y.Saito,K.Nakao,H.Imura.: "Atrial pacing stimulates secretion of atrial natriuretic polypeptide without elevation of atrial pressure in awake dogs with experimental complete atrioventricular block." Circ.Res.66. 115-122 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Nakao,H.Itoh,Y.Kambayashi,K.Hosoda Y.Saito,T.Yamada,M.Mukoyama,H.Arai,G.Shirakami,S.Suga,M.Jougasaki,Y.Ogawa,K.Inouye and H.Imura.: "Rat brain natriuretic peptideーIsolation from rat heart and tissue distributionー." Hypertension. 15. 774-778 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Ogawa,K.Nakao,M.Mukoyama,G.Shirakami,H.Itoh,K.Hosoda,Y.Saito,H.Arai,S Suga,M.Jougasaki,T.Yamada,Y.Kambayashi,K.Inouye,H.Imura: "Rat brain natriuretic peptideーTissue distribution and molecular formー." Endocrinology. 126. 2225-2227 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Mukoyama,K.Nakao,Y.Saito,Y.Ogawa,K.Hosoda,S.Suga,G.Shirakami,M.Jougasaki and H.Imura.: "Human brain natriuretic peptide,a novel cardiac hormone." Lancet. 335. 801-802 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Maeda,M.Niwa,K.Shigematsu,M.Kurihara,Y.Kataoka,K.Nakao,H.Imura,H.Matsuo,H.Tsuchiyama,M.Ozaki.: "Specific [ ^<125>I]brain natriuretic peptideー26 binding sites in rat and pig kidney." Eur.J.Pharmacol.176. 341-350 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Itoh,K.Nakao,M.Mukoyama,Y.Saito,T.Yamada,G.Shirakami,H.Arai,K.Hosoda,S.Suga,I.Yoshida and H.Imura.: "Preparation of monoclonal antibodies against brain natriuretic peptide and their application to radioimmunoassay and passive immunization." Endocrinology. 127. 1292-1300 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Jougasaki,H.Yasue,M.Mukoyama,K.Nakao and K.Takahashi.: "Appearance of atrial natriuretic peptide in the ventricles in patients with myocardial infarction." Am.Heart J.119. 92-96 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Nishimura,Y.Saito,T.Hidaka,T.Ishihara,K.Nakao,H.Imura,Y.Okamoto and T.Ban.: "Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide?" J.Thoracic and Cardiovascular Surgery. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Itoh,K.Nakao,M.Mukoyama,H.Arai,T.Yamada,Y.Saito,S.Shiono,K.Hosoda,G.Shirakami,S.Suga and H.Imura.: "Pathophysiological role of augmented atrial natriuretic polypeptide (ANP) gene expression in DOCAーsalt hypertensionーEffects of ANP monoclonal antibody." Am.J.Hypertension. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Mukoyama,K.Nakao,K.Hosoda,S.Suga,Y.Saito,Y.Ogawa G.Shirakami,M.Jougasaki,K.Obata,H.Yasue,Y.Kambayashi,K.Inouye,H.Imura: "Brain natriuretic peptide(BNP)as a novel cardiac hormone in humansーEvidence for an exquisite dual natriuretic peptide system,atrial natriuretic peptide and brain natriuretic peptide." J.Clin.Invest.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Hosoda,K.Nakao,M.Mukoyama Y.Saito,M.Jougasaki G.Shirakami,S.Suga,Y.Ogawa,H.Yasue and H.Imura.: "Expression of brain natriuretic peptide gene in human heartーProduction in ventricleー." Hypertension. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Iwata et al.: "Effect of brain natriuretic peptide on cyclic GMP accumulation in a kidney epithelial cell line(LLC-PK1)" Eur.J.Pharmacol.159. 321-323 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Saito et al.: "Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart" J.Clin.In vest.83. 298-305 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Yasue et al.: "Increased secretion of atrial natriuretic polypeptide(ANP)from the left ventricle in patients with dilated cardiomyopathy" J.Clin.Invest.83. 46-51 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Itoh et al.: "Radioimmunoassay for brain natriuretic peptide(BNP)-Detection of BNP in canine brain-" Biochem.Biophys.Res.Commun.158. 120-128 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Saito et al.: "Brain natriuretic peptide is a novel cardiac hormone." Biochem.Biophys.Res.Commun.158. 360-368 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Itoh et al.: "Chronic blockade of endogenous atrial natriuretic polypeptide(ANP)by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensiv and DOCA-salt hypertensive rats" J.Clin.Invest.84. 145-154 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Saito et al.: "Endothelin in human plasma and culture medium of aortic endothelial cells:Detection and characterization with radioimmunoassay using monoclonal antibody" Biochem.Biophys.Res.Commun.161. 320-326 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Itoh et al.: "Occurrence of a novel cardiac natriuretic peptide in rats" Biochem.Biophys.Res.Commun.161. 732-739 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Yamada et al.: "Effects of naloxone on vasopressin secretion in conscious rats:Evidence for inhibitory role of endogenous opioid peptides in vasopressin secretion" Endocrinology. 125. 785-790 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Kambayashi et al.: "Isolation and sequence determination of rat cardiac natriuretic peptide" Biochem.Biophys.Res.Commun.163. 233-240 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Saito et al.: "Detection and characterization of endothelin-1 like immunoreactivity in rat plasma" Biochem.Biophys.Res.Commun.163. 371-377 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Nishimura et al.: "Atrial pacing stimulate secretion of atrial natriuretic polypeptide without elevation of atrial pressure in awake dogs with experimental complete atrioventricular block" Circ.Res.(1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] G.Takemura et al.: "Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts:Immunohistochemical study of the endomyocardial biopsy specimens" Circulation. in press. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Saito et al.: "Increased plasma endothelin level in patients with essential" N.Engl.J.Med.322. 205 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] G.Shirakami et al.: "Reduction of sodium intake by intracerebroventricular injection of brain natriuretic peptide(BNP)in salt-depleted rats" Biomed.Res.in press. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Kambayashi et al.: "Isolation and sequence determination of human brain natriuretic peptide in human atrium" FEBS Lett.259. 341-345 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Saito et al.: "Application of monoclonal antibodies for endothelin to hypertensive research" Hypertension. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Nakao et al.: "Rat brain natriuretic peptide-Isolation from rat heart and tissue distribution" Hypertension. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Ogawa et al.: "Rat brain natriuretic peptide-Tissue distribution and molecular form-" Endocrinology. (1990)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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