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Roles of L-DOPA as a neurotransmitter and L-DOPA reuptake systems involved

Research Project

Project/Area Number 18H02580
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionYokohama City University

Principal Investigator

GOSHIMA Yoshio  横浜市立大学, 医学研究科, 教授 (00153750)

Co-Investigator(Kenkyū-buntansha) 増川 太輝  横浜市立大学, 医学部, 助教 (10711898)
小池 正人  順天堂大学, 医学(系)研究科(研究院), 教授 (80347210)
新井 信隆  公益財団法人東京都医学総合研究所, 病院等連携研究センター, 参事研究員 (10167984)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
KeywordsL-ドーパ / 受容体 / GPR143 / トランスポーター / ドパミン作動性神経伝達
Outline of Final Research Achievements

To elucidate the roles of neurotransmitters is one of the most important studies in the field of life sciences and medicine. We propose that L-DOPA, a precursor of dopamine, by itself could act as a neurotransmitter in the central and peripheral nervous system. In this study, we obtained the following results: 1) We found that solute carrier (Slc) proteins, Slc7A9 and Slc3A1 were both expressed in the brain including substantia nigra, striatum, cortex, hypothalamus and other brain areas. 2) In Gpr143 gene-deficient mice, acute and chronic effect of nicotine were attenuated. 3) GPR143-positive immunoreactivities were localized in Lewy body in Parkinson’s disease (PD). These finding further suggest the role of L-DOPA as a neurotransmitter, and L-DOPA and its receptor GPR143 might be involved in the pathogenesis of PD.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病の特効薬であるL-ドーパは、それ自体では活性がなく、その薬効は、生体内でドパミンに変換して生ずると考えられている。私たちは、それに加えて、L-ドーパ自体にもドパミンとは異なる作用があることを示してきた。私たちはこの研究で、L-ドーパを細胞内に取り込む作用を持つトランスポーター候補分子が存在すること、L-ドーパ受容体であるGPR143がドパミンの作用に関与すること、L-ドーパとGPR143がパーキンソン病の病態に関わる可能性を示した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (30 results)

All 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (3 results)

  • [Journal Article] Genetic associations of single nucleotide polymorphisms in the L-DOPA receptor (GPR143) gene with severity of nicotine dependence in Japanese individuals, and attenuation of nicotine reinforcement in Gpr143 gene-deficient mice2020

    • Author(s)
      Masukawa D, Nishizawa D, Kanai K, Kitamura S, Kasahara Y, Hashimoto T, Takahagi R, Hasegawa J, Nakayama K, Sato N, Tanioka F, Sugimura H, Ikeda K, Goshima Y
    • Journal Title

      J Pharmacol Sci

      Volume: 144(2) Issue: 2 Pages: 89-93

    • DOI

      10.1016/j.jphs.2020.07.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution of mRNA for GPR143, a receptor of 3,4-L-dihydroxyphenylalanine, and of immunoreactivities for nicotinic acetylcholine receptors in the nigrostriatal and mesolimbic regions2020

    • Author(s)
      Kasahara Yuka、Masukawa Daiki、Nakamura Yoshie、Murata Koshi、Hashimoto Tatsuo、Takizawa Kohtaro、Koga Motokazu、Nakamura Fumio、Fukazawa Yugo、Funakoshi Kengo、Goshima Yoshio
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 370-375

    • DOI

      10.1016/j.neures.2020.08.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of the gene product of ocular albinism 1 (GPR143/OA1) but not its mutant forms inhibits neurite outgrowth in PC12?cells2019

    • Author(s)
      Masukawa Daiki、Yamada Kaisei、Goshima Yoshio
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 141 Issue: 1 Pages: 41-48

    • DOI

      10.1016/j.jphs.2019.09.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoreactivity of a G protein-coupled l-DOPA receptor GPR143, in Lewy bodies2019

    • Author(s)
      Goshima Yoshio、Watanabe Shuya、Seki Erika、Koga Motokazu、Masukawa Daiki、Nakamura Fumio、Komori Takashi、Arai Nobutaka
    • Journal Title

      Neuroscience Research

      Volume: 148 Pages: 49-53

    • DOI

      10.1016/j.neures.2018.12.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] l-DOPA and Its Receptor GPR143: Implications for Pathogenesis and Therapy in Parkinson’s Disease2019

    • Author(s)
      Goshima Yoshio、Masukawa Daiki、Kasahara Yuka、Hashimoto Tatsuo、Aladeokin Aderemi Caleb
    • Journal Title

      Frontiers in Pharmacology

      Volume: 10 Pages: 1-9

    • DOI

      10.3389/fphar.2019.01119

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 分子から迫る神経薬理学 ドーパ神経伝達物質仮説:ドーパ受容体は存在するか?2018

    • Author(s)
      増川太輝,五嶋良郎
    • Journal Title

      Clinical Neuroscience

      Volume: 36 Pages: 878-879

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 分子から迫る神経薬理学 ドーパ受容体の生理学的および薬理学的作用.2018

    • Author(s)
      増川太輝,五嶋良郎
    • Journal Title

      Clinical Neuroscience

      Volume: 36 Pages: 1004-1005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 分子から迫る神経薬理学 ドーパ受容体候補分子からみるドーパ療法の応用および問題点.2018

    • Author(s)
      増川太輝,五嶋良郎
    • Journal Title

      Clinical Neuroscience

      Volume: 36 Pages: 1130-1132

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Functional analysis of GPR143, an L-DOPA receptor, in GPCRs hetero-oligomers2021

    • Author(s)
      増川太輝、五嶋良郎
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] L-DOPAの存在、遊離と作用2021

    • Author(s)
      五嶋良郎
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ニコチンの効果における GPR143の関与および喫煙患者におけるGPR143 の一塩基多型解析2020

    • Author(s)
      増川太輝、五嶋良郎 他
    • Organizer
      第43回神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 発達期海馬神経新生におけるL-ドーパ受容体GPR143の関与2020

    • Author(s)
      笠原由佳、五嶋良郎
    • Organizer
      第43回神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] GPR143, a L-DOPA receptor, is involved in monocrotaline-induced pulmonary hypertension2020

    • Author(s)
      Nakano M, Hashimoto T, Koga M, Masukawa D, Oku S, Mizuno Y, Goto T, Tamura K, Goshima Y
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Involvement of GPR143 in the hippocampal pathophysiological alteration after limb2020

    • Author(s)
      Shibata R, Kasahara Y, Goshima Y
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] An optogenetic approach for functional analysis of L-DOPAergic neurotransmission in the nucleus tractus solitarii.2019

    • Author(s)
      Masukawa D, Nakao Y, Muneto H, Kim R, Bito H, Goshima Y
    • Organizer
      第42回日本神経科学大会・第62回日本神経化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ドーパ受容体 GPR143 遺伝子欠損マウスにおけるニコチンの効果 および喫煙患者における GPR143 の一塩基多型解析.2019

    • Author(s)
      増川太輝, 西澤大輔, 笠原由佳,北村慧,金井香央里,池田和隆, 五嶋良郎
    • Organizer
      第140回日本薬理学会関東部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GPR143, an L-DOPA receptor, may help control inflammation in adenine-induced chronic kidney disease.2019

    • Author(s)
      Hashimoto T, Nakano M, Suzuki S, Yamada T, Masukawa D, Koga M, Ito R, Haruhara K, Wakui H, Tamura K, Goshima Y
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] An optogenetic approach to identify L-DOPA as a neurotransmitter in the nucleus tractus solitarii.2019

    • Author(s)
      Masukawa M, Nakao Y, Muneto H, Kim R, Bito H, Goshima Y
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The role of L-DOPA as a neurotransmitter.2018

    • Author(s)
      Goshima Y, Masukawa D, Koga M, Hashimoto T
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] L-DOPA cyclohexyl ester, an L-DOPA antagonist, protects neurostimmulated contractile response in mice heart.2018

    • Author(s)
      Hashimoto T, Hamaguchi S, Masukawa D, Koga M, Nakano M, Tanaka H, Tamura K, Goshima Y
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immunoreactive signals of GPR143 in the tegmental area, substantia nigra and their trajectories.Immunoreactive signals of GPR143 in the tegmental area, substantia nigra and their trajectories.2018

    • Author(s)
      Takizawa K, Koga M, Masukawa D, Nakamura F, Goshima Y
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tyrosine hydroxylase and/or rBAT positive neuron in primary afferent innervates in the nucleus tractus solitarii.2018

    • Author(s)
      Masukawa D, Nakao Y, Goshima Y
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ドーパ受容体候補分子の同定とニコチン作用における役割.2018

    • Author(s)
      五嶋良郎, 増川太輝, 古賀資和, 橋本達夫, 小倉顕一
    • Organizer
      公益財団法人喫煙科学研究財団・第33回平成29年度助成研究発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The localization and innervation of rBAT and tyrosine hydroxylase positive neuron in the nucleus tractus solitarii.2018

    • Author(s)
      Masukawa D, Nakao Y, Goshima Y
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] L-DOPA受容体候補分子GPR143の中脳ドパミン神経核及びその投射野における分布.2018

    • Author(s)
      瀧澤光太郎, 古賀資和, 増川太輝, 中村史雄, 五嶋良郎
    • Organizer
      第139回日本薬理学会関東部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 延髄孤束核におけるL-DOPA神経伝達機構の解明.2018

    • Author(s)
      増川太輝, 中尾友香, 宗藤大樹,金亮,尾藤晴彦,五嶋良郎
    • Organizer
      第139回日本薬理学会関東部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ADRA1を介した血圧の昼夜変動の新たな制御機構-L-ドーパは交感神経応答を制御する-2018

    • Author(s)
      五嶋良郎
    • Organizer
      第54回高血圧関連疾患モデル学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] 横浜市立大学 分子薬理神経生物学 ホームページ

    • URL

      http://www-user.yokohama-cu.ac.jp/~pharmac/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 横浜市立大学分子薬理神経生物学教室ホームページ

    • Related Report
      2019 Annual Research Report
  • [Remarks] 横浜市立大学分子薬理神経生物学教室ホームページ

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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