Journal
NEUROSCIENCE LETTERS
Volume 516, Issue 1, Pages 94-98Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2012.03.065
Keywords
Microglial BV2 cell; Voltage-gated proton channel; Dextromethorphan; Dextrorphan; 3-Hydroxymorphinan
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Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0022213]
- National Research Foundation of Korea [2010-0022213] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 IC50 value of 51.7 mu M 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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