Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.
Summary of "Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells."
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 51.7μM 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.
Department of Pharmacology, College of Medicine, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul 156-756, Republic of Korea.
This article was published in the following journal.
Name: Neuroscience letters
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22487729
- DOI: http://dx.doi.org/10.1016/j.neulet.2012.03.065
Medical and Biotech [MESH] Definitions
Ether-a-go-go Potassium Channels
A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.
Voltage-dependent Anion Channels
A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.
Ion Channel Gating
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
Shaker Superfamily Of Potassium Channels
Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.
A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates voltage-gated SODIUM CHANNELS. It has been used to induce arhythmias in experimental animals and it has antiinflammatory and antineuralgic properties.
Dextromethorphan exhibits neuroprotective effects against inflammation-mediated neurodegeneration. However, relatively little is known regarding the molecular mechanism for this inflammation-mediated...
Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na(+) channel is essentia...
Interleukin-1β (IL-1β) is an important proinflammatory cytokine and plays key roles in physiological and pathophysiological processes of central nervous system (CNS). The voltage-gated Na(+) channel...
Previous studies have shown that 17β-estradiol has a pivotal function by blocking voltage-gated K(+) (Kv) channels in several different types of cells such as cardiac myocytes and neurons. Outward Kv...
Modulation of voltage-gated Ca(2+) channels controls activities of excitable cells. We show that high-voltage activated Ca(2+) channels are regulated by membrane phosphatidylinositol 4,5-bisphosphate...
A study to study the potential effect of PF-00299804 inhibition of CYP2D6 on dextromethorphan.
The radical treatment for Hepatocellular carcinoma (HCC) is surgery. However, it is only for 10 to 20% of all patients and 10 to 30% of them have relapsed every year after surgery. For an...
The only curative option for pancreatic cancer patients is surgery, but the patients within 20% of them are possible for a radical surgery. Accordingly, concurrent chemo-radiation therapy...
This study will assess transcranial magnetic stimulation (TMS) as a biomarker and characterize TMS readouts of the activity of MK2637 and dextromethorphan. Resting quantitative electroence...
This drug-drug interaction study is being conducted to evaluate the potential effect of Dimebon on the pharmacokinetics on dextromethorphan, a probe substrate of the cytochrome P450 2D6 (C...