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Coordination between ecto-nucleotidases and purinergic receptor-mediated signaling

Research Project

Project/Area Number 14570082
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionFukushima Medical University School of Medicine

Principal Investigator

MATSUOKA Isao  Fukushima Med.Univ., Pharmacol., Assistant Professor, 医学部, 助教授 (10145633)

Co-Investigator(Kenkyū-buntansha) WATANO Tomokazu  Fukushima Med.Univ., Pharmacol., Research Assistant, 助手 (60301404)
ONO Tomoyuki  Fukushima Med.Univ., Pharmacol., Medical Technician, 主任医療技師
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsATP / adenosine / ecto-nucleotidase / P2 purinoceptor / P1 purinoceptor / Xenopus oocyte / membrane localization / mRNA / 内皮細胞 / 活性酸素 / リゾリン脂質
Research Abstract

Extracellular ATP produces diverse physiological effects by activating multiple P2 receptors. Although P2 receptor activation is terminated by hydrolysis of ATP by ecto-nucleotidases, this metabolic step results in adenosine (Ade) production, thereby initiating the P1 receptor activation. We demonstrated that extracellular ATP stimulates A_<2A> and A_<2B> receptor through a rapid and localized Ade production on membrane surface. Furthermore, ecto-alkaline phosphatase (eALP) was found to act as ecto-nucleotidases. Heterologous expression of A_<2A> and A_<2B> receptors in Xenopus oocyte revealed that ATP can stimulate each P1 receptor as rapidly as direct stimulation with Ade in an ecto-nucleotidase-dependent manner. The ecto-nucleotidase-dependent P1 receptor activation by ATP was resistant to elimination of Ade by Ade deaminase (ADA). Analysis of extracellular [^3H]ATP metabolism in NG108-15 cells and Xenopus oocyte showed that the metabolically generated [^3H]Ade was retained on the membrane surface even in the presence of ADA. When NG108-15 cells were transfected with eALP-GFP fusion protein, eALP-GFP was localized on membrane surface and co-internalized with A_<2A> receptors upon prolonged A_<2A> receptor activation. These findings suggest that the close association of P1 receptors to ecto-nucleotidases may comprise a functional receptor for ATP, and some physiological responses to ATP would occur through this mechanism.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (21 results)

All 2004 2003 2002 Other

All Journal Article (12 results) Publications (9 results)

  • [Journal Article] ATP-and adenosine-mediated signaling in the central nervous system : Adenosine receptor activation by ATP through rapid and localized generation of adenosine by ecto-nucleotidases.2004

    • Author(s)
      Matsuoka I, Ohkubo S
    • Journal Title

      Jpn J Pharmacol 94(2)

      Pages: 95-99

    • NAID

      10012114195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] 神経系におけるエクトヌクレオチダーゼ2004

    • Author(s)
      松岡 功
    • Journal Title

      臨床化学 33(1)

      Pages: 127-134

    • NAID

      10012862635

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Ecto-nucleotidase in the nervous system2004

    • Author(s)
      Matsuoka I
    • Journal Title

      Jpn J Clin Chem 33

      Pages: 127-134

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] ATP- and adenosine-mediated signaling in the central nervous system : adenosine receptor activation by ATP through rapid and localized generation of adenosine by ecto-nucleotidases.2004

    • Author(s)
      Matsuoka I, Ohkubo S
    • Journal Title

      J Pharmacol Sci. 94

      Pages: 95-99

    • NAID

      10012114195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] ATP receptor-mediated cellular responses and their regulation by ecto-nucleotidases2003

    • Author(s)
      Matsuoka I
    • Journal Title

      Fukushime Med J 53

      Pages: 125-142

    • NAID

      10016229200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Adenine nucleotide-induced activation of adenosine A2B receptors expressed in Xenopus laevis oocytes : involvement of a rapid and localized adenosine formation by ectonucleotidases.2002

    • Author(s)
      Matsuoka I, Ohkubo S, et al.
    • Journal Title

      Mol Pharmacol 61(3)

      Pages: 606-613

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Characteristics of ATP-induced current through P2X7 receptor in NG108-15 cells : unique antagonist sensitivity and lack of pore formation.2002

    • Author(s)
      Watano T, Matsuoka I, et al.
    • Journal Title

      Jpn J Pharmacol 88(1)

      Pages: 296-301

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in Guinea pig ventricular myocytes.2002

    • Author(s)
      Li L, Matsuoka I, et al.
    • Journal Title

      Mol Pharmacol 62(1)

      Pages: 602-607

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Adenine nucleotide-induced activation of adenosine A_<2B> receptors expressed in Xenopus laevis oocytes : involvement of a rapid and localized adenosine formation by ectonucleotidases.2002

    • Author(s)
      Matsuoka I, Ohkubo S, Kimura J, Uezono Y.
    • Journal Title

      Mol Pharmacol. 61

      Pages: 606-613

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Characteristics of ATP-induced current through P2X_7 receptor in NG108-15 cells : unique antagonist sensitivity and lack of pore formation2002

    • Author(s)
      Watano T, Matsuoka I, Kimura J.
    • Journal Title

      Jpn J Pharmacol.

      Pages: 428-435

    • NAID

      10008415187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in Guinea pig ventricular myocytes.2002

    • Author(s)
      Li L, Matsuoka I, Suzuki Y, Watanabe Y, Ishibashi T, Yokoyama K, Maruyama Y, Kimura J.
    • Journal Title

      Mol Pharmacol. 62

      Pages: 602-607

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Effects of anions on ATP-induced [Ca^<2+>] increase in NG108-15 cells.2002

    • Author(s)
      Watano T, Matsuoka I, Ogawa K, Kimura J.
    • Journal Title

      Jpn J Pharmacol. 89

      Pages: 302-308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Li L, Matsuoka I, et al.: "Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in guinea pig ventricular myocytes"Mol Pharmacol. 62(3). 602-607 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe Y, Matsuoka I, Kimura J.: "Chronic administration of amiodarone does not affect Na^+/Ca^<2+> exchange current in guinea pig cardiac ventricular myocytes"Jpn J Pharmacol. 90(1). 21-27 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 松岡 功: "ATP受容体を介する細胞応答と細胞外ATP代謝酵素の役割"福島医学雑誌. 53(2). 125-142 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuoka I, Ohkubo S: "ATP-and adenosine-mediated signaling in the central nervous system : Adenosine receptor activation by ATP through rapid and localized generation of adenosine by ecto-nucleotidases"Jpn J Pharmacol. 94(2). 95-99 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 松岡 功: "神経系におけるエクトヌクレオチダーゼ"臨床化学. 33(1). 127-134 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watano T, Matsuoka I, et al.: "Effects of anions on ATP-induced [Ca^<2+>], increase in NG108-15 cells"Jpn J Pharmacol. 89(3). 302-308 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watano T, Matsuoka I. et al.: "Inhibitory effects of metals on ATP-induced current through P2X7 receptor in NG1O8-15 cells."Jpn J Pharmacol. 89 (3). 296-301 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watano T, Matsuoka I, et al.: "Characteristics of ATP-induced current through P2X7 receptor in NG1O8-15 cells : unique antagonist sensitivity and lack of pore formation"Jpn J Pharmacol. 88(4). 428-435 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yokoyama K, Ishibashi T, Matsuoka I et al.: "HMG-CoA reductase inhibitors suppress intracellular calcium mobilization and membrane current induced by lysophosphatidylcholine in endothelial cells"Circulation. 105(8). 962-967 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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