2023 Fiscal Year Final Research Report
Identification of pharmacologically relevant signaling pathways at opioid receptors
| Project Area | Multi-scale platform for untangling physiological complexity |
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| Project/Area Number |
21H05113
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| Research Category |
Grant-in-Aid for Transformative Research Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (II)
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| Research Institution | Tohoku University |
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Principal Investigator |
Inoue Asuka 東北大学, 薬学研究科, 教授 (50525813)
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| Co-Investigator(Kenkyū-buntansha) |
生田 達也 東北大学, 薬学研究科, 助教 (80894815)
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| Project Period (FY) |
2021-08-23 – 2024-03-31
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| Keywords | GPCR / オピオイド |
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| Outline of Final Research Achievements |
This project explored the intracellular signaling characteristics of the three major opioid receptor subtypes (delta, kappa and mu) and their biased ligands (agonists that selectively activate specific signaling pathways). For three transducers (trimeric G protein, arrestin and GPCR kinase), which are signaling factors to which the opioid receptor directly binds, the activation of individual transducer subtypes was measured. As a result, common and individual signaling properties were found for the three opioid receptors. Through collaboration with the Structural Research Group, the structural basis of the opioid receptors, in which biased ligands induce a bias in signaling, was elucidated.
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| Free Research Field |
シグナル伝達学
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| Academic Significance and Societal Importance of the Research Achievements |
オピオイド受容体は鎮痛薬の重要な標的タンパク質であるが、副作用の機序は不明な点が多い。本研究を通じて、オピオイド受容体は、多様な細胞内シグナル伝達経路を誘導することを見出した。さらに、特定のシグナル伝達を誘導するバイアス型リガンドがオピオイド受容体を活性化する構造基盤を見出した。これらの研究成果は、薬効と副作用を切り分けたオピオイド受容体作動薬の合理的な開発論の構築に寄与する。
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