1989 Fiscal Year Annual Research Report

ANP受容体単クロ-ン抗体の開発とANP受容体細胞膜グアニル酸シクラ-ゼの解析

Research Project

Project/Area Number	01641521
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ジ / 脳性ナトリウム利尿ペプチド / 受容体 / グアニル酸シクラ-ゼ / サイクリックGMP / 単クロ-ン抗体
Research Abstract	ナトリウム利尿ペプチドファミリ-はANPとBNPよりなることが明らかになってきたが、本年度は、我々はヒトBNP、ラットBNPの単離・構造決定に成功した。一方、ナトリウム利尿ペプチド受容体には、膜型グアニル酸シクラ-ゼとcoupleしたbiologicallyactive receptor(B受容体)と、生物活性を持たずクリアランスのみに関与するclearance receptor(C受容体)の存在するとの仮説が提唱されてきた。我々はウシ肺のANP受容体に対する12種類のモノクロ-ナル抗体の開発に成功したが、これはC受容体に対するものであることが判明した。さらに、この中の4抗体はウシのみならずヒト、ラットの受容体をも認識するものであった。この抗体を用いて受容体の体内分布とB/C比と肺、腎、副腎、脳で検討すると、組織により著しい差が観察された。さらにB受容体の2subtypeとC受容体がクロ-ニングされたので、Northern blot法でヒト、ラットの組織で検討すると、3種の受容体の体内分布は組織により著しく異なっていることが確認された。また、ANPとBNPの3受容体に対する選択性も異なっており、生理作用との関連が注目される。以上のように、ナトリウム利尿ペプチドシステムは少なくとも2種類のリガンドと3種類の受容体よりなっており、これらの複雑且つ巧妙な相互作用で体液量、血圧調節に関与する心臓ホルモン、神経ペプチドとして作用しており、その分子機構についてさらに検討をすすめている。

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.Iton 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 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" 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. (1990)
[Publications] Y.Saito et al.: "Increased plasma endothelin level in patients with essential hypertension" N.Engl.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 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 hyper-tensive 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 from-" Endocrinology. (1990)

1989 Fiscal Year Annual Research Report

ANP受容体単クロ-ン抗体の開発とANP受容体細胞膜グアニル酸シクラ-ゼの解析

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.Iton 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 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" 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. (1990)

[Publications] Y.Saito et al.: "Increased plasma endothelin level in patients with essential hypertension" N.Engl.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 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 hyper-tensive 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 from-" Endocrinology. (1990)

中尾一和京都大学, 医学部, 助手 (00172263)