inhibitoryeffectsoflappaconitineontheneuronalisoformsofvoltagegatedsodiumchannels

	inhibitoryeffectsoflappaconitineontheneuronalisoformsofvoltagegatedsodiumchannels
	Li Yanfen 1; Zheng Yueming 2; Yu Yong 3; Gan Yong 2; Gao Zhaobing 2
刊名	中国药理学报英文版
	2019
卷号	040 期号:004 页码:451
关键词	voltage-gated sodium channel 1.7 analgesics lappaconitine tetracaine bupivacaine
ISSN号	1671-4083
英文摘要	Lappac on itine (LA) has bee n widely used for postoperative and can cer pain control. LA exhibits excellent an algesic activity with a Ion ger effective time tha n comm on local an esthetics such as tetracai ne and bupivacai ne. However, the mecha nisms un derlyi ng the featured analgesic activity of LA remain largely unknown. Here, we report that LA is an inhibitor of voltage-gated sodium channel 1.7 (Navi.7) stably expressed in human embryonic kidney (HEK293) cells. LA inhibited Navi.7 in a voltage-dependent manner with an IC50 value (with 95% confidence limits) of 27.67 (15.68-39.66) pmol/L when the cell was clamped at -70 mV. In comparison with the quick and reversible inhibition of Navi .7 by tetracaine and bupivacaine, the inhibitory effect of LA was rather slow and irreversible. It took more tha n 10 min to achieve steady-state in hibition when LA (300 pmol/L) was admi nistered. Un like tetracai ne and bupivacai n 巳 LA affected neither the voltage-depende nt activati on nor the in activation of the cha nn els. Five residues in domai n III and domain IV have been reported to be critical for the effects of the two local anesthetics on Nav channels. But our mutant study revealed that only two residues (F1737, N1742) located in domain IV were necessary for the inhibitory activity of LA. The slow onset, irreversibility, and lack of influe nee on cha nnel activati on and in activati on accompa nied with the differe nt molecular determi nants suggest that LA may in hibit Nav1.7 cha nnels in a manner differe nt from local an esthetics. These results may help to un dersta nd the featured an algesic activity of LA, thus ben efiti ng its applicatio n in the clinic and future drug developme nt.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/284978]
专题	中国科学院上海药物研究所
作者单位	1.School of Life Sciences,Shanghai University 2.中国科学院上海药物研究所 3.Department of Neurosurgery,Zhongshan Hospital,Fudan University
推荐引用方式 GB/T 7714	Li Yanfen,Zheng Yueming,Yu Yong,et al. inhibitoryeffectsoflappaconitineontheneuronalisoformsofvoltagegatedsodiumchannels[J]. 中国药理学报英文版,2019,040(004):451.
APA	Li Yanfen,Zheng Yueming,Yu Yong,Gan Yong,&Gao Zhaobing.(2019).inhibitoryeffectsoflappaconitineontheneuronalisoformsofvoltagegatedsodiumchannels.中国药理学报英文版,040(004),451.
MLA	Li Yanfen,et al."inhibitoryeffectsoflappaconitineontheneuronalisoformsofvoltagegatedsodiumchannels".中国药理学报英文版 040.004(2019):451.