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Analgesic mechanism of tetrabiopterin and cholinergic metabolism inhibitors

Research Project

Project/Area Number 24592334
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionShiga University of Medical Science

Principal Investigator

BELLIER Jean-Pierre  滋賀医科大学, 分子神経科学研究センタ-, 助教 (80346022)

Co-Investigator(Kenkyū-buntansha) 林 維光  , 医学部, 助教 (80242973)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsGTP cyclohydrolase 1 / dorsal root ganglion / アセチルコリン / tetrahydrobiopterin / 後根神経節 / 痛覚伝達 / テトラヒドロビオプテリン / Dorsal root ganglion / Brain Stem
Outline of Final Research Achievements

GCH1 is the first and rate-limiting enzyme in the biosynthetic pathway of tetrahydrobiopterin (BH4), an important cofactor for the synthesis of several modulator in pain neurotransmission. Recently, the importance of GCH1 as pain marker has been recognized. The activity of GCH1 is regulated by its regulatory protein GTP cyclohydrolase regulatory protein (GFRP). Here we studied the regulation mechanism of GCH1/GFRP complexation using immunohistochemistry, proximity ligation assay and blue native electrophoresis. It was observed that GCH1 and GFRP were widely expressed in population of serotoninergic, dopaminergic and nitrinergic neurons, but GCH1/GFRP complex occurs mainly in sensory system. This suggested that complex could be targeted for the develop new analgesic strategy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Immunohistochemical localization of two types of choline acetyltransferase in neurons and sensory cells of the octopus arm2014

    • Author(s)
      Sakaue Y, Bellier JP, Kimura S, D'Este L, Takeuchi Y, Kimura H.
    • Journal Title

      Brain Structure & Function

      Volume: 219(1) Issue: 1 Pages: 323-341

    • DOI

      10.1007/s00429-012-0502-6

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunoreactivity for Choline Acetyltransferase of Peripheral-Type (pChAT) in the Trigeminal Ganglion Neurons of the Non-Human Primate <i>Macaca fascicularis</i>2013

    • Author(s)
      Koga T, Bellier JP, Kimura H, Tooyama I
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 46 Issue: 2 Pages: 59-64

    • DOI

      10.1267/ahc.12044

    • NAID

      130003361073

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of NPR-B in neurons of the dorsal root ganglia of the rat2013

    • Author(s)
      Abdelalim EM, Bellier JP, Tooyama I
    • Journal Title

      Peptides

      Volume: 43 Pages: 56-61

    • DOI

      10.1016/j.peptides.2013.02.013

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peripheral choline acetyltransferase in rat skin demonstrated by immunohistochemistry2013

    • Author(s)
      Hanada K, Kishimoto S, Bellier JP, Kimura H
    • Journal Title

      Cell and Tissue Research

      Volume: 351 Issue: 3 Pages: 497-510

    • DOI

      10.1007/s00441-012-1536-z

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgari2012

    • Author(s)
      Casini A, Vaccaro R, D'Este L, Sakaue Y, Bellier JP, Kimura H, Renda TG
    • Journal Title

      European Journal of Histochemistry

      Volume: 56 Issue: 3 Pages: 34-34

    • DOI

      10.4081/ejh.2012.e34

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] GCH 1 and its regulatory protein in the rat brain stem2014

    • Author(s)
      Bellier JP, Ding WG, Sakaue Y, Yasuhara O, Matsuura H, Tooyama I
    • Organizer
      91st Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      鹿児島大学郡元キャンパス
    • Related Report
      2013 Research-status Report
  • [Presentation] Expression of GTP cyclohydrolase feedback regulatory protein (GFRP) in rat brainstem2012

    • Author(s)
      Bellier JP, Ding WG, Yasuhara O, Matsuo A, Tooyama I.
    • Organizer
      11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      神戸コンベンションセンター
    • Related Report
      2012 Research-status Report
  • [Presentation] Immunohistochemical localization of the GTP cyclohydrolase feedback regulatory portein (GFRP) in the rat brainstem2012

    • Author(s)
      Bellier JP, Yasuhara O, Ding WG, Matsuo A, Tooyama I.
    • Organizer
      14th International Congress of Histochemistry and Cytochemistry
    • Place of Presentation
      京都国立京都国際会館
    • Related Report
      2012 Research-status Report
  • [Book] 蛍光組織化学法と透明化技術で脳の中を観察する2014

    • Author(s)
      Bellier JP, 遠山育夫
    • Total Pages
      5
    • Publisher
      39回組織細胞化学講習会、 学際企画
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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