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

Roles of endothelin receptors in astrocytic activation on brain pathologies

Research Project

Project/Area Number 12670086
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionOsaka University

Principal Investigator

KOYAMA Yutaka  Osaka Univ., Grad. Sch. Of Pharmaceutical Sci., Associate Prof., 薬学研究科, 助教授 (00215435)

Co-Investigator(Kenkyū-buntansha) BABA Akemichi  Osaka Univ., Grad. Sch. Of Pharmaceutical Sci., Prof., 薬学研究科, 教授 (70107100)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsEndothelin / Astrocyte / Brain injury / Neurotrophic drug / focal adhesion kinase / neurotrophic factors
Research Abstract

1. Endothelin-induced production of neurotrophic factors : Endothelin (ET) stimulated production of GDNF and BDNF, well-known neurotrophic factors, in rat cultured astorcytes. ET-induced GDNF production was inhibited by removal of intracellular Ca^<2+> and inhibition of ERK signal pathway. An inhibitor of NFkB (pyrrolidin dithiocarbamate) and pre-treatment with glucocorticoid had no effect on the ET-induced GDNF production, while GDNF production induced by H_2O_2 was prevented by them. Continuousinfusion of ETs into cerebral ventricle for 7 days increased GDNF and BDNF in hippocampus and striatum, respectively. Immunohistechemical examinations showed that these neurotrophic factors were produced by astrocytes. These findings suggest that activation of astrocytic ET receptors can be one target of neurotrophic drugs to stimulate neurotrophic factors.
2. Endothelin-induced astrocytic proliferation : The mechanisms of ET-indeuced astrocytic proliferation by focusing roles of focal adhesion kinase (FAK), a tyrosine kinase associated with focal adhesions. ET stimulated phosphorylation of both FAK and ERK in astrocytes. Cytochalasin D inhibited ET-induced phosphorylation of FAK, but not that of ERK. Cytochalasin D reduced the incorporation of bromdeoxyuridine (BrdU) induced by ET-1. A transient transfection with wild-type FAK was followed byan increase in astrocytic BrdU incorporation. The effect of ET-1 on BrdU incorporation was diminished in astrocytes transfected with dominant-negative FAK mutants. ET-1 increased expression of cyclin D1 and D3 proteins in cultured astrocytes. Transfection with wild-type FAK increased expression of cyclin D3 in astrocytes, while that of cyclin D1 was not affected. The ET-induced increase in cyclin D3 expression, but not D1, was prevented by dominant-negative FAK mutants. These results suggest an involvement of FAK in astrocytic proliferation induced by ETs.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Koyama Y.: "Transient treatments with L-glutamate and threo-β--hydroxyaspartate induce swelling of rat cultured astrocytes"Neurochem. Int.. 36. 167-173 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Endothelins increase tyrosine phosphorylation of astrocytic focal adhesion kinase and paxillin accompanied with their association with cytoskeletal components"Neuroscience. 101. 219-227 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小山 豊: "グルタミン酸トランスポーター"蛋白質 核酸 酵素. 45. 1133-1139 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "L-Iactate inhibits L-cystine /L-glutamate exchange transport and decreases glutathione content in rat cultured astrocytes"J. Neurosci. Res.. 59. 685-691 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura H.: "The Na^+-Ca^<2+> exchange inhibitor KB-R7943 inhibits high K^+-induced increases in intracellular Ca^<2+> concentration and [^3H]noradrenaline release in the human neuroblastoma SH-SY5Y"Neurochem. Res. 25. 385-387 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakaue M.: "The Na^+-Ca^<2+> exchanger isoforms in rat neuronal preparations : different changes in their expression during postnatal development"Brain. Res.. 881. 212-216 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Serum-deprivation induces eell death of rat cultured microglia accompained with expression of Bax protein"Jpn J. Pharmacol. 83. 351-354 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Endothelin ET_B receptors in glial cells : a new target target for neurotrophic drugs"Current Topics In Pharmacology. 15. 119-127 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuda T.: "SEAO400, a Novel and Selective Inhibitor of the Na+-Ca2+ Exchanger, Attenuates Reperfusion Injury in the in Vitro and in Vivo Cerebrial Ischemic Models"J. Pharmacol. Exp. Ther.. 296. 249-256 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小山 豊: "脳障害時のアストログリアの機能変化とその細胞内機構"日薬理誌. 119. 135-143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小山 豊: "アクアポリン-4と脳浮腫"日薬理誌. 118. 289 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小山 豊: "NSAIDによるアミロイドβペプチド42産生の抑制"日薬理誌. 119. 264 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Transient treatments with L-glutamate and threo-β-hydroxyaspartate induce swelling of rat cultured astrocytes"Neurochem. Int.. 36. 167-173 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Endothelins increase tyrosine phosphorylation of astrocytic focal adhesion kinase and paxillin accompanied with their association with cytoskeletal components"Neuroscience. 101. 219-227 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Glutamate transporters"Tanpakushitu Kakusann Kohso. 45. 1133-1139 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "L-lactate inhibits l-cystine / L-glutamate exchange transport and decreases glutathione content in rat cultured astrocytes"J. Neurosci. Res.. 59. 685-691 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura H.: "The Na^+-Ca^<2+> exchange inhibitor KB-R7943 inhibits high K^+-induced increases in intracellular Ca^<2+> concentration and [^3H]noradrenaline release in the human neuroblastoma SH-SY5Y"Neurochem. Res.. 25. 385-387 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakaue M.: "The Na^+-Ca^<2+> Exchanger isoforms in rat neuronal preparations : different changes in their expression during postnatal development"Brain. Res.. 881. 212-216 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Serum-deprivation induces cell death of rat cultured microglia accompained with expression of Bax protein"Jpn j. Pharmacol.. 83. 351-354 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Endothelin ET_B receptors in glial cells : a new target for neurotrophic drugs"Curr. Topics In Pharmacol.. 15. 119-127 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuda T.: "SEA0400, a novel and selective inhibitor of the Na-Ca exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebrial ischemic models"J. Pharmacol. Exp. Ther.. 296. 3249-256 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Aquaorin-4 and brain edema"Folia Pharmacol. Japonica. 118. 289 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Functional alterations of astrogila on brain pathologies and their intracellular mechanisms"Folia Pharmacol. Japonica. 119. 135-143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koyama Y.: "Inhibition of amyloidβ42 production by NSAID"Folia Pharmacol. Japonica. 119. 264 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小山 豊: "アクアポリン-4と脳浮腫"日薬理誌. 118. 289 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matusda T.: "SEA0400, a novel and selective inhibitor of the Na^+-Ca^<Z+> exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models"J.Pharmacol. Exp. Ther.. 298. 249-256 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小山 豊: "脳傷害時のアストログリアの機能変化とその細胞内機構"日薬理誌. 119. 135-143 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小山 豊: "NSAIDによるアミロイドβペプチド42産生の抑制"日薬理誌. 119. 264 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koyama Y.: "Endothelins increase tyrosine phosphorylation of astrocytic focal adhesion kinase and paxillin accompanied with their association with cytoskeletal components."Neuroscience. 101. 219-227 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koyama Y.: "Serum-deprivation induces cell death of rat cultured microglia accompanied with expression of bax protein."Jpn.J.Pharmacol.. 83. 351-354 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koyama Y.: "L-Lactate inhibits L-cystine/L-glutamate exchange transport and decreases glutathione contents in rat cultured astrocytes."J.Neurosci.Res.. 59. 685-691 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koyama Y.: "Transient treatments with L-glutamate and threo-β-hydroxy-aspartate induced swelling of rat cultured astrocytes."Neurochem.Int.. 36. 167-173 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小山豊: "脳とエンドセリン."脳21. 4. 73-78 (2001)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi