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High doses of salicylate and aspirin are inhibitory on acid‐sensing ion channels and protective against acidosis‐induced neuronal injury in the rat cortical neuron
Author(s) -
Wang Wei,
Ye ShanDong,
Zhou KeQing,
Wu LiMin,
Huang YiNa
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22742
Subject(s) - aspirin , neuroprotection , pharmacology , acid sensing ion channel , medicine , inhibitory postsynaptic potential , chemistry , depolarization , anesthesia , neuroscience , ion channel , biology , receptor
Aspirin and its main metabolite salicylate are widely used to relieve pain, treat inflammatory diseases, and prevent ischemic stroke. Multiple pathways are responsible for the therapeutic actions exerted by these drugs. One of the pathways is targeting neuronal receptors/ion channels in the central nervous system. Correspondingly, increasing evidence has implicated acid‐sensing ion channels (ASICs) in the processes of the diseases that are medicated by aspirin and salicylate. We therefore employed whole‐cell patch‐clamp recordings to examine the effects of salicylate as well as aspirin on ASICs in cultured cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC current by millimolar concentrations of aspirin and salicylate and found that salicylate reduced acidosis‐induced membrane depolarization. These data suggest that ASICs in the cortex are molecular targets of high doses of aspirin and salicylate. In addition, the results from lactate dehydrogenase release measurement showed that high doses of aspirin and salicylate protected the cortical neuron from acidosis‐induced neuronal injury. These findings may contribute to a better understanding of the therapeutic mechanisms of aspirin and salicylate actions in the brain and provide new evidence on aspirin and salicylate used as neuroprotective agents in the treatment of ischemic stroke. © 2011 Wiley Periodicals, Inc.