• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

多機能蛋白としてのCFTRとその調節

Research Project

Project/Area Number 10217204
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (B)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

大谷 秀夫  京都大学, 医学研究科, 助手 (60293867)

Co-Investigator(Kenkyū-buntansha) 鷹野 誠  京都大学, 医学研究科, 講師 (30236252)
堀江 稔  京都大学, 医学研究科, 講師 (90183938)
Project Period (FY) 1998 – 2002
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥30,100,000 (Direct Cost: ¥30,100,000)
Fiscal Year 2000: ¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 1999: ¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 1998: ¥10,400,000 (Direct Cost: ¥10,400,000)
KeywordsCFTR / cystic fibrosis / genistein / SUR / ABC蛋白 / ゲニスタイン / チロキシンキナーゼ阻害 / イオンチャネル / ATP感受性Kチャネル / Kir6.1 / ミトコンドリア
Research Abstract

Cystic fibrosis Transmembrane regulator(CFTR)は、欧米に多い嚢胞性線維症(cystic fibrosis)の原因遺伝子であることが判明し、さらに、自らがクロライド・チャネルをコードすることが分かり、いわゆるイオン・チャネル病という概念を確定する契機となった遺伝子である。我々の施設を含めて幾つかのラボから、このCFTRが心筋にも発現していることが明らかとされた。そこで電気生理実験に供することが技術的に簡単であった心筋細胞を用いてのCFTR研究を行った。また、CFTRは、ATP-binding cassetteを有する、いわゆるABC protein familyのメンバーであり、同じく、このメンバーであり最近、分子基盤が同定された、SUR(sulfonylurea receptor)の働きについても、とくにその機能調節をするATP感受性Kチャネル分子との関連で検討を進めた。Protein tyrosine kinase阻害薬であるgenisteinは、CFTR活性を抑制したが、その作用部位は、kinase inhibitionを介するものではなく、CFTRのATP-binding domainである可能性を報告した(Obayashi et al,Eur J Physiol,1999)。また、遺伝子工学的手法を用いて作成した種々のmutantsを用いて、薬剤の作用部位やABC蛋白の器質としてのATPの感受性の違いを検討した(Xie et al,Proc Natl Acad USA,1999;Horie et al,J Cardiovasc Pharma,2000;Kono et al,Eur J Physiol,2000;Haruan et al,Eur J Physiol,2000)。

Report

(3 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Obayashi K. et al.: "On the mechanism of genistein-induced activation of protein kinase A-dependent Cl^- conductance in cardiac myocytes."European Journal of Physiology. 438. 269-277 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xie LH et al: "Phospholipase C-linked receptors regulate the ATP-sensitive patassium channel uia depletion of phosphatidylinositol・4,5-biphospha"Proceedings National Academy of USA. 96. 15292-15297 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horie M. et al.: "Blockade of cardiac ATP-sensitive K^+ channels by cibenzoline targets its pore-forming subunit."Journal of Cardiovascular Pharmacol. 35. 434-442 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kono Y. et al.: "The properties of kir6,r6.2 tandem channel co-expressed with SUR2A."European Journal of Physiology. 440. 692-698 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Haruna T. et al.: "Alteration of membrane lipid environment by lpalmitoylcar-nitine modulates KATP channels in guineapig uentricular myocytes."European Journal of Physiology. 441. 200-207 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akao M, et al.: "Angiotensin II type 1 receptor blockade abolishes specific KATP channe gene exression in rats with myocardial infarction."Journal of Molecular and Cellular Cardiology. 32. 2239-2247 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horie M. et al.: "Long QT syndrome as a cause of cardiac sudden death."Heart Failure, Frontiers in Cardiology.. 8 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsuchiya K et al.: "Functional Communication Between Cardiac ATP-Sensitive K^+ Channel and Na/K ATPase"Journal of Cardiovascular Electrophysiology. 9. 415-422 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishida-Takahashi A et al.: "Cystic fibrosis transmembrane conductance regulator mediates sulfonylurea block of the inwardly rectifying K+ channel, Kir6.1"Journal of Physiology. 508. 23-30 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ai T et al.: "Accentuated antagonism by angiotensin II on cardiac L-type Ca-currents enhanced by g-adrenergic stimulation"Pflugers Archiv. 436. 168-174 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ai T et al.: "Successful radiofrequency current catheter ablation of accessory atrioventricular pathway after tricuspid replacement in Ebstein's anomaly"Japanese Circulation Journal. 62. 791-793 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Washizuka T et al.: "Genistein inhibits slow component delayed-rectifier K currents via a tyrosine kinase-independent pathway"J Mol Cell Cardiol. 30. 2577-2590 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haruna T et al.: "Coordinate interaction between ATP-sensitive K+ channel and Na/K-ATPase modulates ischemic preconditioning"Circulation. 98. 2905-2910 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Obayashi K et al.: "On the mechanism of genistein ?induced activation of protein kinase A-dependent Cl-conductance in cardiac myocytes"Pflugers Archiv. 438. 269-277 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshida H et al.: "A novel missense mutation in the pore region of HERG in a long QT syndrome patient causes a severe dominant negative effect on HERG function"J Cardiovas Electrophysiol. 10. 1262-1270 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Xie LH et al.: "Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4, 5-bisphosphate metabolism"Proceeding s National Academy of USA. 96. 15292-15297 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Horie M et al.: "Blockade of cardiac ATP-sensitive K+ channels by cibenzoline targets its pore-forming subunit"Journal of Cardiovascular Phrmacol. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kono Y et al.: "The properties of Kir6.1-6.2 tandem channel co-expressed with SUR2A"European Journal of Physiology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 堀江稔: "心不全における抗不整脈薬治療-ATP感受性カリウム・チャネルとトランスポータ蛋白の機能的協関-"カレントテラピー. 6. 100-103 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 堀江稔: "嚢胞性線維症とCFTR"最新医学. 54. 55-59 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 堀江稔: "イオンチャネルとチャネル病"循環器専門医. 7. 199-214 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 堀江稔: "イオンチャネル病としての嚢胞性線維症-心筋型CFTRを含めて-"心臓. 3. 870-876 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 堀江稔: "不整脈-21世紀の分子医学"分子心血管病. 1. 31-36 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Horie M et al: "Recent Advances in Heart Failure"Springer Verlag (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Haruna T,Horie M,Nanada R,Kouchi I,Tsuchiya K,Akao H,Otani H.: "Coordinate interaction between ATP-sensitive K^+ channel and Na^+,K^+_-ATPase modulates ischemic preconditioning." Circulation. 98. 2905-2910 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takano M,Xie L-H,Otani H,Horie M: "Cytoplasmic terminus domains of Kir6.x confer different nuoleotide-dependent gating on the ATP-sensitive K^+ channel." Journal of Physiology(Lond.). 512. 395-406 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ai T,Horie M,Obayashi K,Sasayama S: "Accentuated antagonism by angiotensin II or guinea-pig Cardiac L-type Ca-currents enhanced by b-adrenergic stimulution" Pfugers Archiv. 436. 168-174 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishida-Takahashi A,Otani H,Takahashi C,Horie M et al: "Cystic fibrosis transmembrane conductance regulator mediates sulphonylurea block of inwardly restifying……" Journal of Physiology(Lond). 508. 23-30 (1998)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi