Internalization and recycling profiles ofμ-opioid receptors induced by remifentanil ; Implication for the mechanism of tolerance and hyperalgesia

• Project/Area Number: 21792016
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Nagasaki University
• Principal Investigator: KURATA Shinji 長崎大学, 病院, 助教 (20325666)
• Research Collaborator: UEZONO Yasuhito 国立がん研究センター, 研究所, 分野長 (20213340) ; AYUSE Takao 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (20222705) ; KAWAI Mari 長崎大学, 大学院・医歯薬学総合研究科, 大学院生 ; WATANABE Toshihiro 長崎大学, 大学院・医歯薬学総合研究科, 大学院生
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 歯科麻酔学 / レミフェンタニル / 耐性形成 / 痛覚過敏 / オピオイド受容体 / μオピオイド受容体

Research Abstract

Remifentanil occasionally induces acute tolerance and postoperative hyperalgesia. Development of acute tolerance and opioid-induced hyperalgesia might be related to accelerated internalization and impaired recycling ofμ-opioid receptor(MOR). We thus examined the internalization and recycling profiles of MOR induced by remifentanil. We further investigated the effects of co-treatment with S(+)-ketamine and remifentanil on the internalization and recycling of MOR. We demonstrated that higher concentrations of remifentanil caused impairment of MOR recycling, which may explain acute tolerance or hyperalgesia after infusion of remifentanil at high concentrations in the clinical settings. Furthermore, we found that co-treatment with S(+)-ketamine prevented the impairment of MOR recycling induced by remifentanil. Combinational use with S(+)-ketamine and remifentanil may prevent the acute tolerance and postoperative hyperalgesia.

Research Products

• [Journal Article] GABAB receptors do not internalize after baclofen treatment, possibly due to a lack ofβ-arrestin association : study with a real-time visualizing assay (2012)
  • Author(s): Yuka Sudo, Minoru Hojo, Yuko Ando, Masafumi Takada, Hiroaki Murata, Shinji Kurata, Noriyuki Nishida, Uezono, Yasuhito
  • Journal Title: Synapsei Volume: (in press)
• [Presentation] remifentanilによるμ-オピオイド受容体の細胞内局在の解析-受容体刺激時間および濃度による影響- (2010)
  • Author(s): 倉田眞治, 安藤優子, 高田正史, 北條美能留, 大井久美子, 上園保仁
  • Organizer: 日本麻酔科学会第57回学術集会
  • Place of Presentation: 福岡
• [Presentation] Remifentanil-induced impairement of μ-opioid receptor recycling (2009)
  • Author(s): 倉田眞治
  • Organizer: ASA (American Society of Anesthesiologists) 2009 Annual Meeting
  • Place of Presentation: ニューオリンズアメリカ合衆国
  • Year and Date: 2009-10-17
• [Presentation] レミフェンタニルによるμ-オピオイド受容体の細胞内移行および再感作様式の解析-フェンタニルとの比較およびS(+)-ケタミン併用の影響- (2009)
  • Author(s): 倉田眞治
  • Organizer: 日本麻酔科学会 第56回学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2009-08-16
• [Presentation] Remifentanil-induced impairement ofμ-opioid receptor recycling (2009)
  • Author(s): Kurata S, Ando Y, Sumikawa K, Oi K, Uezono Y.
  • Organizer: The 2009 American Society of Anesthesiologists Annual Meeting
  • Place of Presentation: The 2009 American Society of Anesthesiologists Annual Meeting
• [Presentation] レミフェンタニルによるμオピオイド受容体の細胞内移行および再感作様式の解析.フェンタニルとの比較およびS(+)-ケタミン併用の影響- (2009)
  • Author(s): 倉田眞治, 安藤優子, 高田正史, 北條美能留, 大井久美子, 上園保仁
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸