1989 Fiscal Year Annual Research Report

ナトリウム利尿ペプチドfamilyの生理的、病態生理的意義の解明と臨床応用

Research Project

Project/Area Number	01480288
Research Institution	Kyoto University
Principal Investigator	中尾一和京都大学, 医学部, 助手 (00172263)
Keywords	ナトリウム利尿ペプチド / 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 / 心臓ホルモン / 神経ペプチド
Research Abstract	ANPに続き、ANPと類似した構造を有する脳性ナトリウム利尿ペプチド(BNP)がブタ脳より単離され、ナトリウム利尿ペプチドはナトリウム利尿ペプチドファミリ-より成ることが明らかになった。さらに、ブタBNPは26アミノ酸残基と32アミノ酸残基よりなる2種類が存在すること、ANPの脳内分布と異なること、BNPは心臓にも存在すること、分泌様式はANPと同様のパタ-ンをとること等が明らかになったが、ブタBNPに対する抗血清ではヒトBNP、ラットBNPは検出できず、BNPの一次構造に著しい種属差の存在することが予想された。ブタBNPは脳より単離されたが、心臓の含量の方が大きいことが判明したので、我々はラット心臓、ヒト心臓よりBNPの単離、構造決定を試み、成功した。決定した一次構造はラットBNP:S-Q-D-S-A-F-R-I-Q-E-R-L-R-N-S-K-M-A-H-S-S-S-C-F-G-Q-K-I-D-R-I-G-A-V-S-R-L-G-C-D-G-L-R-L-Fの45アミノ酸残基、ヒトBNP:S-P-K-M-V-Q-G-S-G-C-F-G-R-K-M-D-R-I-S-S-S-S-G-L-G-C-K-V-L-R-R-Hの32アミノ酸残基よりなり、基本構造は似ているものの、ブタBNPとはN端部、C端部の構造が著しく異なることが明らかになった。ラットBNPの体内分布を検討すると、ラットBNPは脳にはほとんど検出されず、脊髄にのみ検出され、BNPの分布にも著しい種属差の存在することが明らかになった。

Research Products
(19 results)

All Other

All Publications (19 results)

[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)
[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)
[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)
[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)
[Publications] Y.Saito et al.: "Brain natriuretic peptide is a novel cardiac hormone." Biochem.Biophys.Res.Commun.158. 360-368 (1989)
[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)
[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)
[Publications] H.Itoh et al.: "Occurrence of a novel cardiac natriuretic peptide in rats" Biochem.Biophys.Res.Commun.161. 732-739 (1989)
[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)
[Publications] Y.Kambayashi et al.: "Isolation and sequence determination of rat cardiac natriuretic peptide" Biochem.Biophys.Res.Commun.163. 233-240 (1989)
[Publications] Y.Saito et al.: "Detection and characterization of endothelin-1 like immunoreactivity in rat plasma" Biochem.Biophys.Res.Commun.163. 371-377 (1989)
[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)
[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)
[Publications] Y.Saito et al.: "Increased plasma endothelin level in patients with essential" N.Engl.J.Med.322. 205 (1990)
[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)
[Publications] Y.Kambayashi et al.: "Isolation and sequence determination of human brain natriuretic peptide in human atrium" FEBS Lett.259. 341-345 (1990)
[Publications] Y.Saito et al.: "Application of monoclonal antibodies for endothelin to hypertensive research" Hypertension. (1990)
[Publications] K.Nakao et al.: "Rat brain natriuretic peptide-Isolation from rat heart and tissue distribution" Hypertension. (1990)
[Publications] Y.Ogawa et al.: "Rat brain natriuretic peptide-Tissue distribution and molecular form-" Endocrinology. (1990)

1989 Fiscal Year Annual Research Report

ナトリウム利尿ペプチドfamilyの生理的、病態生理的意義の解明と臨床応用

Principal Investigator

中尾 一和 京都大学, 医学部, 助手 (00172263)

Research Products

[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)

[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)

[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)

[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)

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

[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)

[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)

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

[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)

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

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

[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)

[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)

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

[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)

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

[Publications] Y.Saito et al.: "Application of monoclonal antibodies for endothelin to hypertensive research" Hypertension. (1990)

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

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

中尾一和京都大学, 医学部, 助手 (00172263)