Diarylamidines: high potency inhibitors of acid-sensing ion channels.
Diarylamidines: high potency inhibitors of acid-sensing ion channels.
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DOI：
10.1016/j.neuropharm.2010.01.011
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发表时间：
2010-06
影响因子：
4.7
通讯作者：
MacDonald, John F.
中科院分区：
文献类型：
--
作者：
Chen, Xuanmao;Qiu, Liyan;Li, Minghua;Duerrnagel, Stefan;Orser, Beverley A.;Xiong, Zhi-Gang;MacDonald, John F.
Acid-sensing ion channels (ASICs) are proton-gated cation channels that are predominantly expressed in the nervous system. ASICs are involved in a number of neurological diseases such as pain, ischemic stroke and multiple sclerosis but limited tools are available to target these channels and provide probes for their physiological functions. Here we report that the anti-protozoal diarylamidines, 4′,6-diamidino-2-phenylindole (DAPI), diminazene, hydroxystilbamidine (HSB) and pentamidine potently inhibit ASIC currents in primary cultured hippocampal neurons with apparent affinities of 2.8 µM, 0.3 µM, 1.5 µM and 38 µM, respectively. These four compounds (100 µM) failed to block ENaC channels expressed in oocytes. Sub-maximal concentrations of diminazene also strongly accelerated desensitization of ASIC currents in hippocampal neurons. Diminazene blocked ASIC1a, -1b -2a, and -3 currents expressed in CHO cells with a rank order of potency 1b > 3 > 2a ≥ 1a. Patchdock computational analysis suggested a binding site of diarylamidines on ASICs. This study indicates diarylamidines constitute a novel class of non-amiloride ASIC blockers and suggests that diarylamidines may be developed as therapeutic agents in treatment of ASIC-involved diseases.
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DOI：
10.1085/jgp.200308973
发表时间：
2004-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Paukert M;Babini E;Pusch M;Gründer S
通讯作者：
Gründer S
影响因子：
64.8
作者：
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影响因子：
11.4
作者：
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通讯作者：
Lingueglia, Eric
影响因子：
2.7
作者：
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通讯作者：
Bock, Mark G.
影响因子：
15.9
作者：
Ugawa, S;Ueda, T;Shimada, S
通讯作者：
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