1990 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	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 / モノクロ-ナル抗体 / ノ-ザンブロット解析
Research Abstract	前年度にヒトBrain Natriuretic Peptide(BNP)の単離・構造決定に成功したので本年度は、ヒトBNPの臨床的意義を検討する目的で、ヒトBNPに対するモノクロ-ナル抗体を開発し、RIAを確立した。このRIAを用いて研究した結果、Atrial Natriuretic Peptide(ANP)が主に心房より分泌される心臓ホルモンであると対照的に、BNPは主に心室より分泌される心臓ホルモンであることを証明した。この成績はNorthern blot法によるBNPmRNAとANPmRNAの定量でも確認され、ヒト正常心臓の心室には心臓ANPmRNA総量の3%が検出されるのみであったが、BNPmRNA総量の約80%が心室で検出された。また正常成人の血中BNP濃度は同時に測定したANP濃度の6分の1であるのに対し、心不全、腎不全、高血圧症では血中BNP濃度が上昇し、特に重症心不全では正常レベルの数百倍にも達し、ANP濃度以上の高値を示すことを証明した。また合成ヒトBNPを正常成人に投与するとANPと比較して同等以上の作用が認められ、Pharmacokinetic analysisでは、BNPはANPより半減期が長いことが明らかになった。また本年度には、第3のナトリウム利尿ペプチドであるCーtype Natriuretic Peptide(CNP)がブタ脳より単離されたので抗血清を調整してRIAを確立し、ラット脳、ヒト脳にもCNPが検出されることを報告した。またヒトCNP遺伝子構造を決定し、ヒトpreproCNPは126アミノ酸よりなること、ヒトCNPはブタCNPと同じ構造を有することを明らかにした。CNP遺伝子の5′上流構造(約1.5kb)も明らかにした。

Research Products
(18 results)

All Other

All Publications (18 results)

[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)

1990 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] 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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

[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)

中尾一和京都大学, 医学部, 助手 (00172263)