title: Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.
abstract: 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 μM 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 156-756, Republic of Korea. jinhos@cau.ac.kr
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Song
authors.forename: Jay Z
authors.initials: JZ
authors.lastname: Yeh
mesh_terms: D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage; D002460:Cell Line; D003915:Dextromethorphan / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000502:physiology*
chemical_list: D000996:Antitussive Agents; C540876:Hv1 proton channel, mouse; D007473:Ion Channels; D003915:Dextromethorphan