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A novel alpha-conopeptide Eu1.6 inhibits N-type (Ca(V)2.2) calcium channels and exhibits potent analgesic activity

文献类型：期刊论文

作者Liu, Zhuguo1; Bartels, Peter2; Sadeghi, Mahsa2,3; Du, Tianpeng4; Dai, Qing1; Zhu, Cui1; Yu, Shuo1; Wang, Shuo1; Dong, Mingxin1; Sun, Ting1
刊名SCIENTIFIC REPORTS
出版日期2018-01-17
卷号8
ISSN号2045-2322
DOI10.1038/s41598-017-18479-4
文献子类Article
英文摘要We here describe a novel alpha-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong antin-ociceptive activity by an unexpected mechanism of action. Unlike other alpha-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the alpha 3 beta 4 and alpha 7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L-and T-type calcium channels expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type calcium channel currents in isolated mouse DRG neurons which was independent of GABA(B) receptor activation. In HEK293 cells expressing Ca(V)2.2 channels alone, Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage-and state-dependent manner. Inhibition of Ca(V)2.2 by Eu1.6 was concentration-dependent (IC50 - 1 nM). Significantly, systemic administration of Eu1.6 at doses of 2.5-5.0 mu g/kg exhibited potent analgesic activities in rat partial sciatic nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had no significant side-effect on spontaneous locomotor activity, cardiac and respiratory function, and drug dependence in mice. These findings suggest alpha-conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and chronic pain and opens a novel option for future analgesic drug design.
WOS关键词NICOTINIC ACETYLCHOLINE-RECEPTORS ; NACHR ALPHA-3-BETA-2 ; OMEGA-CONOTOXINS ; CONUS-MARMOREUS ; PAIN ; DIVERSITY ; RAT ; ALPHA-9-ALPHA-10 ; ACTIVATION ; ZICONOTIDE
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000422716900138
出版者NATURE PUBLISHING GROUP
资助机构National Basic Research Program of China(2010CB529802) ; National Basic Research Program of China(2010CB529802) ; High Technology Program of Oceans in China(2011AA09070108) ; High Technology Program of Oceans in China(2011AA09070108) ; National Natural Science Foundation of China(81473192 ; National Natural Science Foundation of China(81473192 ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; 81202506) ; 81202506) ; National Basic Research Program of China(2010CB529802) ; National Basic Research Program of China(2010CB529802) ; High Technology Program of Oceans in China(2011AA09070108) ; High Technology Program of Oceans in China(2011AA09070108) ; National Natural Science Foundation of China(81473192 ; National Natural Science Foundation of China(81473192 ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; 81202506) ; 81202506) ; National Basic Research Program of China(2010CB529802) ; National Basic Research Program of China(2010CB529802) ; High Technology Program of Oceans in China(2011AA09070108) ; High Technology Program of Oceans in China(2011AA09070108) ; National Natural Science Foundation of China(81473192 ; National Natural Science Foundation of China(81473192 ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; 81202506) ; 81202506) ; National Basic Research Program of China(2010CB529802) ; National Basic Research Program of China(2010CB529802) ; High Technology Program of Oceans in China(2011AA09070108) ; High Technology Program of Oceans in China(2011AA09070108) ; National Natural Science Foundation of China(81473192 ; National Natural Science Foundation of China(81473192 ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; National Health and Medical Research Council of Australia (NHMRC)(APP1072113) ; 81202506) ; 81202506)
源URL[http://ir.wipm.ac.cn/handle/112942/12810]  
专题中国科学院武汉物理与数学研究所
通讯作者Jiang, Ling; Adams, David J.; Dai, Qiuyun
作者单位1.Beijing Inst Biotechnol, Beijing 100071, Peoples R China
2.RMIT Univ, Hlth Innovat Res Inst, Melbourne, Vic 3083, Australia
3.Univ Wollongong, IHMRI, Wollongong, NSW 2522, Australia
4.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China
5.Inst Dis Control & Prevent, Beijing 100071, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Zhuguo,Bartels, Peter,Sadeghi, Mahsa,et al. A novel alpha-conopeptide Eu1.6 inhibits N-type (Ca(V)2.2) calcium channels and exhibits potent analgesic activity[J]. SCIENTIFIC REPORTS,2018,8.
APA Liu, Zhuguo.,Bartels, Peter.,Sadeghi, Mahsa.,Du, Tianpeng.,Dai, Qing.,...&Dai, Qiuyun.(2018).A novel alpha-conopeptide Eu1.6 inhibits N-type (Ca(V)2.2) calcium channels and exhibits potent analgesic activity.SCIENTIFIC REPORTS,8.
MLA Liu, Zhuguo,et al."A novel alpha-conopeptide Eu1.6 inhibits N-type (Ca(V)2.2) calcium channels and exhibits potent analgesic activity".SCIENTIFIC REPORTS 8(2018).

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来源：武汉物理与数学研究所

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