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ドーパ自体のカルシウムチャネル電流増大作用-孤束核パッチクランプを用いた解析-

Research Project

Project/Area Number 11780563
Research Category

Grant-in-Aid for Encouragement of Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionYokohama City University

Principal Investigator

宮前 丈明  横浜市立大学, 医学部, 助手 (00239435)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsドーパ受容体 / カルシウムチャネル / 孤束核 / パッチクランプ / 競合的ドーパ拮抗薬 / ドーパ / 神経伝達物質 / 弧束核
Research Abstract

従来ドパミンの前駆体にすぎないとされてきたアミノ酸「ドーパ」の神経伝達物質仮説を提起、検証してきた。本研究においては、ラット孤束核単離細胞のパッチクランプを施行し、ドーパの電位依存性カルシウムチャネル(HVA)電流増大作用の解析を行ない、以下の知見を得た。1)ドーパ(L体,1μM)適用によって生じるHVA電流(I_<Ba>)増大(約30%)は、-50mVから-30mVにかけての、HVAチャネル活性が比較的低い電位においてより顕著であった。2)このドーパ応答の大半は、競合的ドーパ拮抗薬DOPA methyl ester処置によって抑制された。3)同濃度のドパミンはHVA電流に対して無作用、一方、noradrenalineはHVA電流を顕著に抑制した。従ってこのドーパ作用はカテコラミンへの変換を介さない、ドーパ自体の作用であると考えられる。4)このドーパ応答は、10,100nM,1μMと濃度依存的に増大した。5)パッチピペット内GDP-βS添加は、ドーパのHVA電流増大成分を抑制した。孤束核単離細胞に発現するドーパ受容体はGタンパク質連関型受容体である可能性が高い。本研究によって、孤束核におけるドーパの興奮性作用機序解明にあたっての電気生理学的および分子基盤となる成果が得られた。

Report

(2 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Miyamae T: "L-DOPAergic components in the caudal ventrolateral medulla in Daroreflex neurotransmission"Neuroscience. 92. 137-149 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furukawa N: "L-DOPA cyclohexyl ester is a novel potent and relatively stable competitive antagonist against L-DOPA among several L-DOPA ester compounds."Spn.J.Pharmacol.. 82. 40-47 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishii H: "Involvement of rBAT in Na^+-dependent and-independent transport of a neurotransmitter candidate L-DOPA in Xeropus laens axytes injected with rabbit small intestinal epithelium poly A^+R"Biochim.Biophys. Acta.. 1466. 61-70 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furukawa N: "Endogenously released DOPA is a causal factor for glutamate release and resultant neuronal cell death by transient ischemia in rat striata"J.Neurochem.. 76. 815-824 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugaya Y: "Autoradiographic studies using L-^<14>C-and ^3H-DOPA reveal regional Na^+-dependent uptake of the neurotransmitter candidate L-DOPA in the central nerions system."Neuroscience. 00. 000-000 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arai N: "DOPA cyclohexyl ester, a competitive DOPA antagonist, protects glutamate release and resultant neuronal death by transient ischemia in hippocampas CA1.of Conscious rats"Neurosci.Lett.. 00. 000-000 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamae T: "L-DOPAergic components in the candal ventrolateral medulia in baroreflex neurbtransmission."Neuroscience. 92. 137-149 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyamae T: "Some interactions of L-DOPA and its related compaurds with glutamate receptors."Life Sci.. 64. 1045-1054 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furukawa N: "L-DOPA cyclohexyl ester is a novel potent and relatively stable compettfive artagonist against L-DOPA among several L-DOPA ester compounds"Jpn. J. Pharmacol.. 82. 40-47 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishii H: "Involvement of rBAT in Na^+-dependent and -independent transport of a newn transmitter candidate L-DOPA in xenhpus..."Biochim. Biophys. Acta. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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