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Structure determination and structure-activity relationship of DOP Arelated compounds

Research Project

Project/Area Number 18390076
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

GOSHIMA Yoshio  Yokohama City University, Graduate School of Medicine, Professor (00153750)

Co-Investigator(Kenkyū-buntansha) YAGAMI Tatsuro  Himeji-Dokkyou University, Department of Pharmacy, Professor (00363812)
KAJIWARA Yasuhiro  Yokohama City University, International Graduate School of Arts and Sciences, Professor (50275020)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,100,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsL-3,4-dihydroxyphenylalanine / neurotransmitter / structure-activity relationship / L-threo-DOPS / nucleus tractus solitarii / central cardiovascular control / drug discovery / high performance liquid chromatoeraphy / 生理活性物質 / GPCR / 線虫 / 血圧制御 / カルシウムシグナル / 海馬
Research Abstract

We have proposed that L-3,4-dihydroxyphenylalanine (DOPA), the precursor of dopamine, is a neurotransmitter in the central nervous system. However its specific receptor(s) have not been determined yet. In this proposal, we have tried to identify specific ligands for DOPA recognistion site(s), namely DOPAreceptor(s), and investigate structure-activity relationship by using blood-pressure monitoring system in anaesthetized rats. DOPA or L-threo-DOPS, a precursor of noradrenaline, when microinjected into the nucleus tractus solitarii (NTS), induces depressor and baradycardic responses. By using HPLC, we found an active fraction of DOPA or DOPS-containing solution other than that of DOPA and DOPS itself that induced depressor and bradycardic responses. We obtained A113 and S122 fractions from DOPA and DOPS-containing solutions, respectively, both of which were active in inducing the cardiovascular responses in anaesthetized rats. In addition, these responses were antagonized by L-DOPA cycl … More ohexylester (DOPA CHE), an competitive antagonist for DOPA, thereby suggesting that some unknown active substances in DOPA and DOPS solution induced depressor and bradycardic responses through the recognition site(s) for DOPA. We are now trying further purification, identification and structural determination of these substances.
The second project aimed at identification and characterization of a DOPA receptor candidate gene, C06H5.7 in C elegans. Using Xenopus laevis oocyte expression system, we identified a candidate G-protein-coupled receptor, that mediates current response to DOPA C06H5.7 was expressed in ASH chemosensory neurons. In C06H5.7 mutant animals, the avoidance response to undiluted benzaldehyde, but not to 1-octanol, was attenuated. C06H5.7, when exogenously expressed in ASH neurons, rescued the responsiveness to benzaldehyde. Furthermore, we found some water-soluble substance as a novel repellent acting on this receptor in C elegans. These results indicate that C06H5.7 is not a receptor for DOPA but the first chemosensory receptor that mediates aversive response to volatile and water soluble chemorepellents. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (18 results)

All 2008 2007 2006 Other

All Journal Article (11 results) (of which Peer Reviewed: 4 results) Presentation (4 results) Book (3 results)

  • [Journal Article] Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant: implications for essential hvnertension2008

    • Author(s)
      Araki N, Umemura M, Goshima Y, et. al.
    • Journal Title

      Hypertension 51

      Pages: 773-777

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant: implications for essential hypertension2008

    • Author(s)
      Araki, N., Umemura, M., Goshima, Y., et. al.
    • Journal Title

      Hypertension 51

      Pages: 773-777

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant: implications for essential hypertension.2008

    • Author(s)
      Araki N, Umemura M, Goshima Y, et. al.
    • Journal Title

      Hypertension 51

      Pages: 773-777

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A possible involvement of non-enzymatic derivatives of DOPA and DOPS in DOPAereic responses2007

    • Author(s)
      Murota Y, Yagami T, Goshima Y, et. al.
    • Journal Title

      J Pharmacol Sci Suppl I

      Pages: 1-54

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A possible involvement of non-enzymatic derivatives of DOPA and DOPS in DOPAergic responses2007

    • Author(s)
      Murota, Y., Yagami, T., Goshima, Y., et. al.
    • Journal Title

      J Pharmacol Sci, Suppl I

      Pages: 1-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A possible involvement of non-enzymatic derivatives of DOPA and DOPS in DOPAergic responses.2007

    • Author(s)
      Murota Y, Yagami T, Goshima Y, et. al.
    • Journal Title

      J Pharmacol Sci Suppl I

      Pages: 1-54

    • Related Report
      2007 Annual Research Report
  • [Journal Article] L- 3,4-Dihydroxyphenylalanine -induced c-Fos expression in the CNS under inhibition of central aromatic L-amino acid decar boxylase2006

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

      Neuropharmacol 50

      Pages: 909-916

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] L-3,4-Dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic L-amino acid decarboxylase2006

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

      Neuropharmacol 50

      Pages: 909-916

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] L-3, 4-Dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic L-amino acid decarboxylase2006

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

      Neuropharmacol 50

      Pages: 909-916

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] L-3,4-dihydroxyphenylalanine-induced c-Fos expression in the CNS under inhibition of central aromatic L-amino aciddecarboxylase.2006

    • Author(s)
      Shimamura M, Shimizu M, Yagami T, Funabashi T, Kimura F, Kuroiwa Y, Misu Y, Goshima Y.
    • Journal Title

      Neuropharmacology 50・8

      Pages: 909-916

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differential effects of methamphetamine and cocaine on behavior and extracellular levels of dopamine and 3,4-dihydroxyphenylalanine in the nucleus accumbens of conscious rats.2006

    • Author(s)
      Izawa J, Yamanashi K, Asakura T, Misu Y, Goshima Y.
    • Journal Title

      Eur J Pharmacol. 549・1-3

      Pages: 84-90

    • Related Report
      2006 Annual Research Report
  • [Presentation] ドーパ応答能におけるドーパ及びドプス比酵素的誘導体の関与2007

    • Author(s)
      室田 裕大
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Aromatic derivatives of DOPS could induce DOPAergic responses2007

    • Author(s)
      Murota, Y., Yagami, T., Aoki, R., Kajiwara, Y., Yamamoto, N., Goshima, Y
    • Place of Presentation
      Yokohama, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A possible involvement of non-enzymatic derivatives of DOPA And DOPAergic responses

    • Author(s)
      Murota, Y., Yagami, T., Aoki, R., Sugiyama, Y., Kajiwara, Y., Yamamoto, N., Goshima, Y
    • Organizer
      The 80th Japanese Pharmacological Society, March
    • Place of Presentation
      Nagoya, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The 30th Molecular Biology Society of Japan

    • Author(s)
      Aoki, R., Yagami, T., Miyamae, T., Nakamura, F., Ogura, K., Kajiwara, Y., Yamamoto, N., Sasakura, H., Mori, I., Goshima, Y
    • Place of Presentation
      Yokohama, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Neurobiology of DOPA as a Neurotransmitter2006

    • Author(s)
      Misu Y, Goshima Y
    • Total Pages
      384
    • Publisher
      CRC
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] Neurobiology of DOPA as a Neurotransmitter2006

    • Author(s)
      Misu, Y., Goshima, Y
    • Publisher
      CRC Press
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Neurobiology of DOPA As A Neurotransmitter2006

    • Author(s)
      Misu Y, Goshima
    • Total Pages
      384
    • Publisher
      CRC Press
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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