Endothelin-1 enhances acid-sensing ion channel currents in rat primary sensory neurons  

作　　者：Lei Wu Ting-ting Liu Ying Jin Shuang Wei Chun-yu Qiu Wang-ping Hu 

机构地区：[1]Research Center of Basic Medical Sciences,School of Basic Medical Sciences,Hubei University of Science and Technology,Xianning 437100,China [2]Department of Pharmacology,Hubei University of Science and Technology,Xianning 437100,China

出　　处：《Acta Pharmacologica Sinica》2020年第8期1049-1057,共9页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China(No.81671101 and No.31471062).

摘　　要：Endothelin-1(ET-1),an endogenous vasoactive peptide,has been found to play an important role in peripheral pain signaling.Acid-sensing ion channels(ASIlCs)are key sensors for extracellular protons and contrbute to pain caused by tissue acidosis.It remains unclear whether an interaction exists between ET-1 and ASIlCs in primary sensory neurons.In this study,we reported that ET-1 enhanced the activity of ASiCs in rat dorsal root ganglia(DRG)neurons.In whole-cell voltage-clamp recording,ASiC currents were evoked by brief local application of pH6.0 external solution in the presence of TRPVI channel blocker AMG9810.Pre-application with ET-1(1-100 nM)dose-dependently increased the proton-evoked ASlCcurrents with an ECso value of 7.42±0.21nM.Pre-application with ET-1(30 nM)shifted the concentration-response curve of proton upwards with a maximal current response increase of 61.11%±4.33%.We showed that ET-1 enhanced ASIC currents through endothelin-A receptor(ETAR),but not endothelin-B receptor(ETR)in both DRG neurons and CHO cell co-expressing ASiC3 and ETR.ET-1 enhancement was inhibited by blockade of G-protein or protein kinase C signaling.In current-clamp recording,pre-application with ET-1(30 nM)significantly increased acid-evoked firing in rat DRG neurons.Finally,we showed that pharmacological blockade of ASiCs by amiloride or APETx2 signicantly alleviated ET-1-induced flinching and mechanical hyperalgesia in rats.These results suggest thatET-1 sensitizes ASICs in primary sensory neurons via ETAR and PKC signaling pathway,which may contribute to peripheral ET-1-induced nociceptive behavior in rats.

关 键 词：ENDOTHELIN-1 acid-sensing ion channels dorsal root ganglion neuron nociceptive response BQ-123 BQ-788 AMILORIDE APETx2 

分 类 号：R96[医药卫生—药理学]