Does Acetaldehyde Mediate Ethanol Action in the Central Nervous System?
Copyright policy )Does Acetaldehyde Mediate Ethanol Action in the Central Nervous System?
Background: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand‐gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde.Methods: The effects of acetaldehyde (1–1000 μM) were tested by two‐electrode voltage‐clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand‐gated ion channel receptors [α1 glycine; α1β2γ2Sγ‐aminobutyric acid (GABA)A; ρ1 GABAc; 5‐hydroxytryptamine‐3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and α4β2, α4β4, and α2β4 nicotinic‐acetylcholine] and the G‐protein–coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT.Results: Acetaldehyde (1 and 10 μM) significantly enhanced α1 glycine receptor–mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT‐mediated dopamine uptake.Conclusions: Our results suggest a potential minor role for acetaldehyde in the glycine receptor–mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.
- University of California, San Francisco United States
- University of California System United States
- The University of Texas at Austin United States
- Wake Forest University United States
- University of Cagliari Italy
Central Nervous System, Dopamine Plasma Membrane Transport Proteins, Membrane Glycoproteins, Patch-Clamp Techniques, Potassium Channels, Ethanol, Electric Conductivity, Gene Expression, Membrane Transport Proteins, Nerve Tissue Proteins, Acetaldehyde, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Receptors, GABA, Oocytes, Animals, Humans, Drug Interactions, Female, Receptors, Cholinergic, Potassium Channels, Inwardly Rectifying
Central Nervous System, Dopamine Plasma Membrane Transport Proteins, Membrane Glycoproteins, Patch-Clamp Techniques, Potassium Channels, Ethanol, Electric Conductivity, Gene Expression, Membrane Transport Proteins, Nerve Tissue Proteins, Acetaldehyde, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Receptors, GABA, Oocytes, Animals, Humans, Drug Interactions, Female, Receptors, Cholinergic, Potassium Channels, Inwardly Rectifying
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