Analysis of the role of Gs and Gi protein coupled receptors in the mechanism of action of anesthetics and analgesics
| Project/Area Number |
15K10522
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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 | Jichi Medical University |
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Principal Investigator |
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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)
宮野 加奈子 国立研究開発法人国立がん研究センター, 研究所, 研究員 (50597888)
横山 徹 自治医科大学, 医学部, 助教 (80425321)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 麻酔薬 / Gs蛋白共役型受容体 / Gi蛋白共役型受容体 / トラマドール / オピオイド受容体 / ヒドロモルフォン / モルヒネ / フェンタニル / オキシコドン / Gタンパク質依存的シグナル / アフリカツメガエル卵母細胞発現系 / Gs結合型GPCR / ヒドロモルフォ / 後根神経節細胞 / Gi結合型GPCR / 鎮痛薬 / オピオイド / アセトアミノフェン / G蛋白共役型受容体(GPCR) / ドーパミン受容体 |
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| Outline of Final Research Achievements |
In this study, we examined the effects of tramadol and its main active metabolite O-desmethyltramadol (M1), on the function of μORs using Xenopus oocytes expressing cloned human μORs. The effects of tramadol and M1 were evaluated using the Ca(2+)-activated Cl(-) current assay method for G(i/o)-protein-coupled receptors by using a μOR fused to G(qi5) (μOR-G(qi5)) in Xenopus oocytes. Tramadol and M1 also evoked Cl currents in the oocytes expressing μOR-G(qi5); however, relatively higher concentrations (compared to DMAGO [(D-Ala(2), N-MePhe(4), Gly(5)-ol)-enkephalin] ) were necessary to induce such currents. Tramadol and M1 had a direct effect on μORs expressed in Xenopus oocytes. The μOR signal by Hydromorphone was examined. Hydromorphone increased the electrical resistance in a concentration-dependent manner, suppressed the amount of cAMP.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はGs蛋白またはGi蛋白をカルシウム動員型Gq蛋白と融合させたキメラＧ蛋白共役型受容体を作製して、アフリカツメガエル卵母細胞発現系に発現させ、GsならびにGi結合型GPCRに対する作用を細胞内カルシウムの変動で測定する方法で、麻酔薬、鎮痛薬のＧ蛋白共役型受容体に対する影響を観察するものである。今回の研究では、トラマドールとO-デスメチルトラマドール（M1）がこの結果からトラマドールとM1はμORに直接影響を及ぼすことが明らかになった。これらの方法は麻酔薬や鎮痛薬に広く応用ができ、今後の麻酔薬、鎮痛薬の機能解析の一助になるものと考えられる。
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Report
(5 results)
Research Products
(11 results)
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[Journal Article] Tramadol and its metabolite m1 selectively suppress transient receptor potential ankyrin 1 activity, but not transient receptor potential vanilloid 1 activity2015
Author(s)
Miyano K, Minami K, Yokoyama T, Ohbuchi K, Yamaguchi T, Murakami S, Shiraishi S, Yamamoto M, Matoba M, Uezono Y.
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Journal Title
Anesth Analg
Volume: 120(4)
Issue: 4
Pages: 790-798
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Characterization of the properties of four opioid analgesics approved in Japan with cells stably expressing μORs using the CellKeyTM and GloSensorTM cAMP assay systems.2018
Author(s)
Manabe, S., Miyano, K., Ogino, T., Ohshima, K., Uzu, M., Nonaka, M., Matsuoka, Y., Sato, T., Morimatsu, H., Uezono, Y.
Organizer
18th World Congress of Basic and Clinical Pharmacology, Kyoto International Conference Center, Kyoto (2018.7.1-6)
Related Report
Int'l Joint Research
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