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.
J Neurosci Res
; 90(1): 267-77, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21969311
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acidosis
/
Canales de Sodio
/
Corteza Cerebral
/
Salicilatos
/
Antiinflamatorios no Esteroideos
/
Aspirina
/
Proteínas del Tejido Nervioso
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
J Neurosci Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
China