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Functional analysis of novel G-coupled receptor candidate for L-DOPA and structural determination of its ligands

Research Project

Project/Area Number 16390068
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionYokohama City University Graduate School of Medicine

Principal Investigator

GOSHIMA Yoshio  Yokohama City University, Molecular Pharmacology, Professor, 大学院・医学研究科, 教授 (00153750)

Co-Investigator(Kenkyū-buntansha) YAGAMI Tatsuro  Yokohama City University, Molecular Pharmacology, Research Associate, 医学部(現姫路獨協大学), 助手(教授) (00363812)
NAKAMURA Fumio  Yokohama City University, Molecular Pharmacology, Assistant Professor, 医学部, 準教授 (10262023)
KAJIWARA Yasuhiro  Yokohama City University, Molecular Pharmacology, Assistant Professor, 大学院・国際総合科学研究科, 準教授 (50275020)
KAMIYA Yoshitaka  Yokohama City University, Molecular Pharmacology, Research Associate, 附属病院, 助手 (90381491)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2005: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsDOPA / Benzaldehyde / Caenorhabditis elegans / chemotaxis / blood pressure control / monoamine receptors / 神経伝達物質 / Gタンパク質連関型受容体 / NMR / DOPA / DOPS / 3,4-dihydroxybenzaldehyde / 3,4-dihydroxybenzoic acid / C06H5.7 / caenorhabditis elegans / xenopus laevis oocyte / non-amine
Research Abstract

We proposed L-3,4-dihydroxyphenylalanine (DOPA) as a neurotransmitter candidate of baroreceptor afferent neurons terminating in the nucleus tractus solitarii (NTS). We have isolated C.elegans C06H5.7 gene as a receptor candidate for DOPA through expression screening using Xenopus laevisoocytes. Electrophysiological analyses of C06H5.7 showed that C06H5.7 responded to non-amine metabolites of DOPA, but did not to itself. Previously, we have reported that 3,4-dihydroxybenzaldehyde (DHBALD) acts as one of active ligands for C06H5.7. An odorant benzaldehyde that is similar to DHBALD in the chemical structure electrophysiologically activated C06H5.7. Although benzaldehyde at low concentrations sensed by AWC sensory neurons is a chemoattractants in C.eleagans, expression of C06H5.7 have not yet been detected in AWC. A null mutant candidate for C06H5.7, nj66,was not defective in the attraction by benzaldehyde. On the other hand, benzaldehyde at high concentrations sensed by ASH sensory neurons is a chemorepellent in C.eleagans, but its receptor has not yet been identified. To test the possibility that C06H5.7 is involved in the aversive mechanisms, we are performing the aversion assay of nj66 and detecting the expression of C06H5.7 in the ASH. However, these ligands produced no effects on blood pressure and hear rates of anesthetized rats, when these were microinjected into the nucleus tractus solitarii.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005 2004

All Journal Article (16 results) Book (2 results)

  • [Journal Article] L-3,4-Dihydroxyphenylealanine-induced c-Fos expression in the CNS under inhibition of central aromatic l-amino acid decarboxylase2006

    • Author(s)
      Shimamura M et al.
    • Journal Title

      Neuropharmacology 50 8

      Pages: 909-916

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Semaphorin3A signaling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2 : implication of common phosphorylation mechanism underlying axon guidance and Alzheimer's disease.2005

    • Author(s)
      Uchida Y
    • Journal Title

      Genes to Cells 10・2

      Pages: 165-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] RCMP2のリン酸化を解した軸策ガイダンスの分子機構2005

    • Author(s)
      内田穣
    • Journal Title

      生化学 77・11

      Pages: 1424-1424

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of ketamine and propofol on inflammatory responses of primary glial cell culgures stimulated with lipopolysaccharide.2005

    • Author(s)
      Shibakawa YS
    • Journal Title

      Br J Anaesth 95・6

      Pages: 803-803

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Phosphorylation of Phosphorylation CRMP2activityin growth cones.2005

    • Author(s)
      Arimura N
    • Journal Title

      Mol Cell Biol 25・22

      Pages: 9973-9973

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 1-3, 4-Dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic l-amino acid decarboxylase.2005

    • Author(s)
      Shimamura M
    • Journal Title

      Neuropharmacology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Semaphorin 3A signaling is mediate via sequential Cdk5 and GSK3beta phosphorylation of CRMP2 : implication of common phosphorylation mechanism underlying axon guidance and Alzheimer's disease2005

    • Author(s)
      Uchida Y et al.
    • Journal Title

      Genes to Cell 10 2

      Pages: 165-179

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular mechanism of axon guidance mediated by phosphorylation of CRMP22005

    • Author(s)
      Uchida Y, Goshima Y
    • Journal Title

      Seikagaku 77 11

      Pages: 1424-1427

    • NAID

      10016886768

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide2005

    • Author(s)
      Shibakawa M et al.
    • Journal Title

      Br J Anaesth 95 6

      Pages: 803-810

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphorylation of Rho kinase regulates CRMP-2 activity in growth cones2005

    • Author(s)
      Arimura N et al.
    • Journal Title

      Mol Cell Biol 25 22

      Pages: 9973-9984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Semaphorin3A signaling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2:implication of common phosphorylation mechanism underlying axon guidance and Alzheimer's disease.2005

    • Author(s)
      Uchida Y
    • Journal Title

      Genes to Cells 10・2

      Pages: 165-165

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CRMP2のリン酸化を介した軸索ガイダンスの分子機構2005

    • Author(s)
      内田穣
    • Journal Title

      生化学 77・11

      Pages: 1424-1424

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phosphorylation ofRho kinaseregulates CRMP-2 activity in growth cones.2005

    • Author(s)
      Arimura N
    • Journal Title

      Mol Cell Biol 25・22

      Pages: 9973-9973

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 1-3,4-Dihydroxyphenylalanine-inducedc-Fosexpressioniin the CNS under inhibition of central aromatic 1-amino acid decarboxylase.2005

    • Author(s)
      Shimamura M
    • Journal Title

      Neuropharmacology (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Contribution of the medial amygdaloid nucleus to the development of hypertension in spontaneously hypertensive rats.2004

    • Author(s)
      Fukumori R
    • Journal Title

      Neuroscience Letter 365

      Pages: 128-131

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of the medial amygdaloid nucleus in restraint stress-induced pressor responses in rats.2004

    • Author(s)
      Kubo T
    • Journal Title

      Neuroscience Letter 354

      Pages: 84-86

    • Related Report
      2004 Annual Research Report
  • [Book] Neurobiology of DOPA as a neurotransmitter2005

    • Author(s)
      Misu Y, Goshima Y
    • Total Pages
      384
    • Publisher
      CRC Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Neurobiology of DOPA as a neurotransmitter2005

    • Author(s)
      Misu Y, Goshima Y
    • Total Pages
      384
    • Publisher
      CRS Press
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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