Nafamostat mesilate reversibly blocks acid-sensing ion channel currents.
Nafamostat mesilate reversibly blocks acid-sensing ion channel currents.
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DOI：
10.1016/j.bbrc.2007.08.133
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发表时间：
2007-11
影响因子：
3.1
通讯作者：
S. Ugawa;Y. Ishida;T. Ueda;Kiyoshi Inoue;M. Nagao;S. Shimada
中科院分区：
文献类型：
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作者：
S. Ugawa;Y. Ishida;T. Ueda;Kiyoshi Inoue;M. Nagao;S. Shimada
我们电生理学研究了甲磺酸萘莫司他（NM：6-脒基-2-萘基对胍基苯甲酸二甲磺酸盐）及其两种代谢产物6-脒基-2-萘酚（AN）和对胍基苯甲酸（PGBA）对三种不同类型的人酸敏感离子通道（ASIC）的影响。在ASIC 1a和ASIC 2a表达卵母细胞中，在保持电位为− 60 mV时，NM以浓度依赖性方式降低酸诱发的内向电流，IC 50（抑制常数）值分别约为13.5和70.6μM。NM应用还对双相ASIC 3电流的初始相瞬态分量产生浓度依赖性抑制，IC 50值约为2.5μM。AN对ASIC 1a、ASIC 2a和瞬态ASIC 3电流的阻断作用较弱，IC_（50）分别为1.2、1.3和0.14mM，而PGBA对它们的电流不敏感。
We electrophysiologically investigated the effects of nafamostat mesilate (NM: 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate) and its two metabolites, 6-amidino-2-naphthol (AN) and p-guanidinobenzoic acid (PGBA), on three distinct types of human acid-sensing ion channels (ASICs). Acid-evoked inward currents at a holding potential of −60mV in ASIC1a- and ASIC2a-expressing oocytes were decreased by extracellular application of NM in a concentration-dependent manner with IC50(inhibition constant) values of approximately 13.5 and 70.6μM, respectively. The NM application also produced concentration-dependent inhibition of the initial-phase transient component of biphasic ASIC3 currents with an IC50value of approximately 2.5μM. Application of AN showed weak blocking effects on the ASIC1a, ASIC2a, and transient ASIC3 currents with IC50values of approximately 1.2, 1.3, and 0.14mM, respectively, whereas PGBA was insensitive to their currents.