Optimization of opioid therapy based on the diversity of dimerized opioid receptors
| Project/Area Number |
25462442
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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| Research Institution | Nagasaki University |
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Principal Investigator |
MURATA Hiroaki 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (90437856)
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| Co-Investigator(Kenkyū-buntansha) |
上園 保仁 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20213340)
須藤 結香 国立研究開発法人国立がん研究センター, その他部局等, その他 (70646695)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | オピオイド受容体 / 二量体 / オピオイド |
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| 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.
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Report
(4 results)
Research Products
(1 results)
