αO-Conotoxin GeXIVA disulfide bond isomers exhibit differential sensitivity for various nicotinic acetylcholine receptors but retain potency and selectivity for the human α9α10 subtype.
αO-Conotoxin GeXIVA disulfide bond isomers exhibit differential sensitivity for various nicotinic acetylcholine receptors but retain potency and selectivity for the human α9α10 subtype.
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αO-芋螺毒素 GeXIVA 二硫键异构体对各种烟碱乙酰胆碱受体表现出不同的敏感性，但保留对人类 α9α10 亚型的效力和选择性
DOI：
10.1016/j.neuropharm.2017.04.015
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发表时间：
2017-12
影响因子：
4.7
通讯作者：
Luo S
中科院分区：
文献类型：
--
作者：
Zhangsun D;Zhu X;Kaas Q;Wu Y;Craik DJ;McIntosh JM;Luo S
Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette’s syndrome, Alzheimer’s and Parkinson’s diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the ‘bead’ disulfide bond isomer displaying the lowest IC50 of the three possible isomers. In the rat chronic constriction injury model of neuropathic pain, this isomer reduced mechanical hyperalgesia without affecting motor performance. Here, we report the effects of the three disulfide bond isomers of GeXIVA on human α9α10 nAChRs, other human nAChR subtypes, various rat nAChR subtypes, and 10 rat α9α10 nAChR mutants. The three isomers displayed only ~5-fold difference in potency on the human vs rat α9α10 receptors and had similar affinities at wild-type rat α9α10 nAChRs and all 10 α9α10 receptor mutants. From these findings, the binding site and mechanism of action of GeXIVA on rat and human α9α10 nAChR was deduced to be different from that of other conotoxins targeting this nAChR subtype. GeXIVA is therefore a unique ligand that might prove useful for further probing of binding sites on the α9α10 nAChR.
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影响因子：
3.7
作者：
Luo S;Christensen S;Zhangsun D;Wu Y;Hu Y;Zhu X;Chhabra S;Norton RS;McIntosh JM
通讯作者：
McIntosh JM
影响因子：
3
作者：
Davis, Jasmine;Jones, Alun;Lewis, Richard J.
通讯作者：
Lewis, Richard J.
DOI：
10.1073/pnas.1501334112
发表时间：
2015-07-21
影响因子：
11.1
作者：
Lavergne, Vincent;Harliwong, Ivon;Alewood, Paul F.
通讯作者：
Alewood, Paul F.
αO-芋螺毒素 GeXIVA 的克隆、合成和表征，一种有效的 α9α10 烟碱乙酰胆碱受体拮抗剂
DOI：
10.1073/pnas.1503617112
发表时间：
2015-07-28
影响因子：
11.1
作者：
Luo, Sulan;Zhangsuna, Dongting;McIntosh, Michael
通讯作者：
McIntosh, Michael
影响因子：
4.7
作者：
Azam L;McIntosh JM
通讯作者：
McIntosh JM