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Publication : Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.

First Author  Song JH Year  2012
Journal  Neurosci Lett Volume  516
Issue  1 Pages  94-8
PubMed ID  22487729 Mgi Jnum  J:344997
Mgi Id  MGI:6877460 Doi  10.1016/j.neulet.2012.03.065
Citation  Song JH, et al. (2012) Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells. Neurosci Lett 516(1):94-8
abstractText  Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC(50) value of 51.7 muM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation.
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