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Development of novel analgesic strategy based on the intracellular localization analysis of opioid receptors using real time visualization assay

Research Project

Project/Area Number 18K08858
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionNagasaki University

Principal Investigator

MURATA Hiroaki  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (90437856)

Co-Investigator(Kenkyū-buntansha) 上園 保仁  東京慈恵会医科大学, 医学部, 教授 (20213340)
宮野 加奈子  東京慈恵会医科大学, 医学部, 准教授 (50597888)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsオピオイド鎮痛薬 / オピオイド受容体 / 脱感作 / 細胞内陥入 / βアレスチン / オピオイド / 受容体 / 細胞内局在 / 二量体
Outline of Final Research Achievements

Remifentanil and fentanyl are two major opioid analgesics often used for perioperative analgesia. We investigated the desensitization profiles of remifentanil and fentanyl to the μ-opioid receptor using human embryonic kidney 293 cells stably expressing HaloTag-tagged μ-opioid receptor. The efficacy and potency during the first administration of remifentanil or fentanyl in activating the μ-opioid receptor were almost equal. Similarly, in β arrestin recruitment, which determines desensitization processes, they showed no significant difference. Repetitive administration of fentanyl resulted in a stronger μ-opioid receptor desensitization potency than that of remifentanil. Subsequently, we demonstrated that remifentanil possessed a higher internalization potency of the μ-opioid receptor than fentanyl by the real-time visualization assay.

Academic Significance and Societal Importance of the Research Achievements

レミフェンタニルとフェンタニルは効果発現時間や作用持続時間など臨床的な特徴はやや異なるものの鎮痛力価は同等といわれ、周術期疼痛管理に用いられる標準的なオピオイド鎮痛薬である。オピオイド鎮痛薬の使用においては耐性形成や痛覚過敏誘発などの問題が指摘されているが、本研究成果はこれらの発生メカニズムに関与する分子機序を示唆するものであり学術的意義がある。また、これらの現象を踏まえた最適な周術期のオピオイド鎮痛薬使用プロトコルを提唱する基盤となる成果が得られたと考えられ、より優れた周術期疼痛管理に貢献できる点で社会的意義もあると言える。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] A novel method for evaluating activity of transient receptor potential channels using a cellular dielectric spectroscopy2020

    • Author(s)
      Miyano Kanako、Ohbuchi Katsuya、Sudo Yuka、Minami Kouichiro、Yokoyama Toru、Yamamoto Masahiro、Uzu Miaki、Nonaka Miki、Shiraishi Seiji、Murata Hiroaki、Higami Yoshikazu、Uezono Yasuhito
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 143 Issue: 4 Pages: 320-324

    • DOI

      10.1016/j.jphs.2020.05.001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] レミフェンタニルおよびフェンタニルによるオピオイド受容体脱感作様式の解析 受容体安定発現細胞を用いて2021

    • Author(s)
      上園 瑛子, 溝渕 有助, 宮野 加奈子, 村田 寛明, 山口 政広, 唐澤 佑輔, 山口 敬介, 井関 雅子, 上園 保仁
    • Organizer
      日本ペインクリニック学会 第55回学術集会
    • Related Report
      2021 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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