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Development of the drug which prevents the induction of acute renal failure and its clinical application

Research Project

Project/Area Number 05557053
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MARUMO Fumiaki  Tokyo Medical and Dental University, 医学部, 教授 (00050443)

Co-Investigator(Kenkyū-buntansha) OOTSUKA Minoru  Research Institute of Fujisawa Pharmacoceutycal Co.Chief Investigator, 主任研究員
SASAKI Sei  Tokyo Medical and Dental University, Associate Professor, 医学部, 助教授 (60170677)
富田 公夫  東京医科歯科大学, 医学部, 助教授 (40114772)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsEndothelin / Kidney / Renal failure / 受容体 / 抗体 / エンドセリン受容体 / 腎機能 / 集合尿細管
Research Abstract

In this research, we intended t o clarify the role of entothelins (ET) and their receptors in the progression of acute renal failure, and to develop the priventive drug for acute renal failure which inhibits the action of ET.
The research has been performed well in respect of clarifying the role of ET in acute renal failure. ET3 is expressed in almost all parts of the kidney, suggesting its important role in kidney function (Ref.1). ET1 production in collectiong duct cells is subjects to many stimulus such as hyperosmolality (Ref.2). ET3 stimulates NO synthesis in glomerular mesangial cells which in turn stimulats cGMP production. These events establish the importance of ET in regulation of kidney functions.
Based on these findings we have tried to raise antibodies against ET receptors (mainly, ETA recptor) which inhibits ET action. We immunized rabbits using several different methods, and obtained a number of antibodies. However, none of these antibodies inhibited the action of ET in kidney fuunction, although some of them recongnised the receptors. It is a general rule that obtaining a good antibody for hydrophobic hormone receptor is extremely difficult. We should try further to obtain a good antibody, but alternative approaches may be considered.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Terada Y.et al.: "Expression of endothelin-3 mRNA along rat nephron segments using polymerase chain reaction." Kidney Int.43. 1273-1280 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yang T.et al.: "Effect of hyperosmolality on production and mRNA expression of ET-1 in inner medullary collecting duct." Am. J. Physiol.264. F684-F689 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Owada A.et al.: "Endothelin(ET)-3 stimulates cyclic guanosine 3n,5′5-monophosphate production via ETb receptor by producing nitric oxide in isolated rat glomerulus,and in cultured rat mesangial cells." J. Clin. Invest. 93. 556-563 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Zou,R.et al.: "Role of endothelin in Masugi nephritis." Tohoku J. Exp. Med.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ida T. et al.: "Expression of ET1 in collecting ducts in acute renal failure." Exp. Nephrol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 1.Terada Y.et al: "Expression of endothelin-3 mRNA along rat nephron segments using polymerase chain reaction" Kidney Int. 43. 1273-1280 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 2.Yang T.et al: "Effect of hyperosmolality on production and mRNA expression of ET-1 in inner medullary collecting duct" Am. J.Physiol. 264. F684-F689 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 3.Owada A.et al: "Endothelin (ET) -3 stimulates cyclic guanosine 3n, 5'5-monophosphate production via ETb receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells" J.Clin. Invest. 93. 556-563 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Zou, R.et al: "Role of endothelin in Masugi nephritis" Tohoku J.Exp. Med. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 5.Ida t. et al: "Expression of ET1 in collecting ducts in acute renal failure" Exp.Nephrol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] R.Zou: "Role of Endothelin in Masugi nephritis" Tohoku,J.Exp.Med.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Ida: "Expression of ET1 in collecting duct in acute renal failure" Exp.Nephrol. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Sei Sasaki: "Cloning,characterization,and chromosomal mapping of human aquaporin of collecting duct." J.Clin,Invest.93. 1250-1256 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masanobu Kawasaki: "Cloning and expression of a protein kinase C-rogulated chloride channel abundantly expressed in rat brain neuronal cells." Neuron. 12. 597-604 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Susumu Adachi: "Two iscforms of a chlorida channel prodominantly expressed in thick asconding linb of Henle's loop and collecting ducts of rat kidney" J.Biol.Chem.269. 17677-17683 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kenichi Ishibashi: "Molecular cfoning and expression of a menber of the aquaporin family with pelmailility to glycerol and ured in additien to water expressed at the basolateral brlmbrane!" Proc.Natl.Acad.Sci.USA. 91. 6269-6273 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinichi Uchida: "Isolation of human aquaporin-CD gene" J.Biol.Chem.269. 23451-23455 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kiyohide Fushimi: "Functional chargcterization and cell immunolocalization of AQP-CD wocter channel in kidney collecting duct." Am.J.Physiol.267. F573-F582 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tomita K.et al: "Effects of ET-1 on water and chloride transport in CCD of the rat" Am.J.Physiol. 264. F690-F696 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Terada Y.et al: "Localization of type-1 AT-II receptor mRNA in rat nephron segments" Kidney Int. 43. 1251-1259 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Terada Y.et al: "Different localization and regulation of two types of AVP receptor mRNA" J.Clim.Invest. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Owada.A.et al: "ET-3 stimulates cGMP production in ET_B receptor" J.Clin.Invest. (in press).

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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