Optimization of opioid therapy based on the diversity of dimerized opioid receptors

2016 Fiscal Year Final Research Report

• Project/Area Number: 25462442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagasaki 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)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: オピオイド受容体 / 二量体

Outline of Final Research Achievements

We cloned HEK293 cells that constantly co-expressed HaloTag-tagged mu opioid receptors (MOR) and T7-tagged delta opioid receptors (DOR) (#25), and constantly co-expressed HaloTag-tagged DOR and FLAG-tagged MOR (#49). Signal transduction analysis using CellkeyTM system revealed that both #25 and #49 possessed MOR and DOR activity. #25 was treated with cell-impermeant HaloTag pH sensor ligand to follow the intracellular dynamics of hetero-dimerized mu-delta receptors that originally located on the membrane surface. DAMGO (a selective MOR agonist), SNC80 (a selective DOR agonist), morphine, fentanyl, and remifentanil induced internalization of heterodimerized MOR/DOR. Internalization induced by SNC80 showed that HaloTag-MOR/T7-DOR made a heterodimer. We are further evaluating the characteristics of intracellular dynamics of heterodimerized MOR/DOR under treatment of various concentrations of opioid agonists.

Free Research Field

麻酔・蘇生学