1989 Fiscal Year Annual Research Report

がん遺伝子産物としてのアンギオテンシン受容体およびANP・BNP受容体の意義

Research Project

Project/Area Number	01015046
Research Institution	Kyoto University
Principal Investigator	中尾一和京都大学, 医学部, 助手 (00172263)
Keywords	がん遺伝子 / 細胞増殖 / ナトリウム利尿ペプチド / アンギオテンシン / 受容体 / プロティンキナーゼ / グアニル酸シクラーゼ / サイクリックGMP
Research Abstract	細胞増殖制限因子としての生理活性ペプチドの意義を探る目的で、新しいナトリウム利尿ペプチドの単離、構造決定、レセプターに対するモノクローナル抗体の開発、それを用いた受容体cDNAのクローニングによる構造決定を試みた。新しいナトリウム利尿ペプチドの単離・構造決定:ラット心房及びヒト心房組織より、BNPを単離し、構造決定に成功した。決定した一次構造はrat BNP:S-Q-D-SーAーFーRーIーQーEーRーLー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、human BNP:SーPーKーMーVーQーGーSーGーCーFーGーRーKーMーDーRーIーSーSーSーSーGーLーGーCーKーVーLーRーRー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、26アミノ酸と32アミノ酸の2種類よりなるporcine BNP、35アミノ酸よりなるbovine BNPと比較しても、多様な分子型を有することが明らかになった。受容体の多様性:我々はウシの肺より精製した受容体に対する12種類のモノクローナル抗体の開発に成功したが、このうちの4種はウシのみならずヒト、ラットの受容体とも結合することが明らかになった。さらに、これらの受容体抗体はdimerとして存在するC受容体に特異的であることが明らかになった。現在、このモノクローナル抗体を用いて、ラットC受容体のcDNAのクローニングを行なっている。また、これらのモノクローナル抗体を用いた免疫沈降反応と合成リガンドを用いた結合実験により、肺、腎、副腎を対象として受容体の組み合わせを検討したが、著しい組織差が存在することが明らかになった。ラットの肺ではB受容体27%C受容体73%、腎ではB受容体7%C受容体93%、副腎ではB受容体93%C受容体7%と標的臓器により受容体の組成が著しく異なることを明らかにした。

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-PK_1)" 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.Invest.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)ーーーーーDetection of BNP in canine brainーーーーー" 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 hypertensive 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" Eydocrinology. 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 wethout 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 homodynamics histology in dilated human hearts:Immunohistochemical study of the endomyocardial biopsy specimens" Circulation. (1990)
[Publications] Y.Saito et al.: "Increased plasma endothelin level in patients with essential hyertension" 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.(1990)
[Publications] Y.Kambayashi et al.: "Isolation and srquence 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.Nakaoet al.: "Rat brain natriuretic peptide ーーーIsolation from rat heart and tissue distribution" Hypertension. (1990)
[Publications] Y.Ogawa et al.: "Rat brain natriuretic peptideーーーTissue distribution and molecular formーーー" Endocrinology. (1990)

1989 Fiscal Year Annual Research Report

がん遺伝子産物としてのアンギオテンシン受容体およびANP・BNP受容体の意義

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-PK_1)" 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.Invest.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)ーーーーーDetection of BNP in canine brainーーーーー" 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 hypertensive 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" Eydocrinology. 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 wethout 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 homodynamics histology in dilated human hearts:Immunohistochemical study of the endomyocardial biopsy specimens" Circulation. (1990)

[Publications] Y.Saito et al.: "Increased plasma endothelin level in patients with essential hyertension" 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.(1990)

[Publications] Y.Kambayashi et al.: "Isolation and srquence 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.Nakaoet al.: "Rat brain natriuretic peptide ーーーIsolation from rat heart and tissue distribution" Hypertension. (1990)

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

中尾一和京都大学, 医学部, 助手 (00172263)