Functional analysis of interaction between DOPA and Glutamate neurotransmission in the nucleus tractus solitarii

• Project/Area Number: 15K21273
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology; Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: MASUKAWA Daiki 横浜市立大学, 医学部, 助手 (10711898)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: L-DOPA / Glutamate / GPR143 / 下位脳幹弧束核 / 圧受容器反射 / 自律神経 / NTS / blood pressure / primary affarent / OA1 / NMDA / 延髄弧束核 / 心血管応答中枢

Outline of Final Research Achievements

Levodopa (DOPA) is currently the most used treatment for Parkinson's disease. We have hypothesis that DOPA is a neurotransmitter in the brain. In this study, we demonstrated that DOPA potentiates the action of glutamate in the nucleus tractus solitarii, which controls central blood pressure regulation.
We also identified the role of DOPA in cardiovascular regulation. We demonstrated that DOPA augments the action of the adrenergic α1 receptor through a DOPA receptor GPR143. It suggested that this mechanism may be involved in diurnal variation of blood pressure.
These findings indicate that DOPA plays an important role in physiological blood pressure control.

Research Products

• [Journal Article] L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor (2017)
  • Author(s): Masukawa Daiki、Koga Motokazu、Sezaki Anna、Nakao Yuka、Kamikubo Yuji、Hashimoto Tatsuo、Okuyama-Oki Yuki、Aladeokin Aderemi Caleb、Nakamura Fumio、Yokoyama Utako、Wakui Hiromichi、Ichinose Hiroshi、Sakurai Takashi、Umemura Satoshi、Tamura Koichi、Ishikawa Yoshihiro、Goshima Yoshio
  • Journal Title: JCI Insight Volume: 2 Issue: 18 Pages: 1-16
  • DOI: 10.1172/jci.insight.90903
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ドーパ-GPR143シグナルはアドレナリンα1受容体応答を増強する (2017)
  • Author(s): 増川太輝、中村史雄、横山詩子、上窪裕二、古賀資和、石川義弘、櫻井隆、五嶋良郎
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎新聞文化ホール（長崎県長崎市）
  • Year and Date: 2017-03-15
• [Presentation] ドーパ受容体 GPR143 とアドレナリン α1 受容体との機能的連関と複合体形成 (2017)
  • Author(s): 増川太輝、古賀資和、涌井広道、上窪裕二、横山詩子、中村史雄、櫻井隆、田村功一、石川義弘、五嶋良郎
  • Organizer: 第 136 回日本薬理学会関東部会
• [Presentation] DOPA-GPR143 signal augments α1-adrenergic receptor response (2017)
  • Author(s): 増川太輝、中村史雄、横山詩子、古賀資和、石川義弘、五嶋良郎
  • Organizer: 第 90 回日本薬理学会年会
• [Presentation] ドーパ受容体 GPR143 はアドレナリン α1 受容体応答を増強する (2016)
  • Author(s): 増川太輝、古賀資和、横山詩子、上窪裕二、中村史雄、櫻井隆、石川義弘、五嶋良郎
  • Organizer: 第135回薬理学会関東部会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）