大麻素受体结构与信号转导的新见解
New Insights in Cannabinoid Receptor Structure and Signaling.
机构信息
Institute of Biochemistry and Molecular Biology, College of Life Sciences, Zhejiang University, Zijingang Campus, Hangzhou, Zhejiang, China.
出版信息
Curr Mol Pharmacol. 2019;12(3):239-248. doi: 10.2174/1874467212666190215112036.
Abstract
BACKGROUND
Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic target for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes. Interestingly, new investigations have indicated that CB1 is functionally present within the mitochondria of striated and heart muscles directly regulating intramitochondrial signaling and respiration.
CONCLUSION
In this review, we summarize the recent progress in cannabinoid-related orphan GPCRs, CB1/CB2 structure, Gi/Gs coupling, allosteric ligands and biased signaling, and mitochondria-localized CB1, and discuss the future promise of this research.
摘要
背景
大麻素长期以来一直被用于医疗目的。大麻素信号被认为是治疗疼痛、成瘾、肥胖、炎症和其他疾病的治疗靶点。最近的研究表明，除了 CB1 和 CB2 之外，还有非 CB1 和非 CB2 大麻素相关孤儿 GPCR 包括 GPR18、GPR55 和 GPR119。此外，CB1 和 CB2 显示变构结合和偏向信号，揭示了偏向信号与功能结果之间的相关性。有趣的是，新的研究表明，CB1 在线粒体中功能性存在于横纹肌和心肌中，直接调节线粒体内部信号和呼吸。
结论
在这篇综述中，我们总结了大麻素相关孤儿 GPCR、CB1/CB2 结构、Gi/Gs 偶联、变构配体和偏向信号以及定位于线粒体的 CB1 的最新进展，并讨论了该研究的未来前景。
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本文引用的文献
1
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Cell. 2019 Jan 24;176(3):459-467.e13. doi: 10.1016/j.cell.2018.12.011. Epub 2019 Jan 10.
2
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Cell. 2019 Jan 24;176(3):448-458.e12. doi: 10.1016/j.cell.2018.11.040. Epub 2019 Jan 10.
3
Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus.大麻素 1 型受体在突变型小鼠海马亚细胞星形胶质细胞隔室中的定位。
Glia. 2018 Jul;66(7):1417-1431. doi: 10.1002/glia.23314. Epub 2018 Feb 26.
4
The G protein-coupled receptors deorphanization landscape.G 蛋白偶联受体的非孤儿化全景。
Biochem Pharmacol. 2018 Jul;153:62-74. doi: 10.1016/j.bcp.2018.02.016. Epub 2018 Feb 15.
5
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Cannabis Cannabinoid Res. 2017 Oct 1;2(1):265-273. doi: 10.1089/can.2017.0036. eCollection 2017.
6
Structural Basis for G Protein-Coupled Receptor Activation.G蛋白偶联受体激活的结构基础。
Biochemistry. 2017 Oct 24;56(42):5628-5634. doi: 10.1021/acs.biochem.7b00747. Epub 2017 Oct 10.
7
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9
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Cannabis Cannabinoid Res. 2016 Jan 1;1(1):22-30. doi: 10.1089/can.2015.0005. eCollection 2016.
10
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