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 microM) were tested by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [alpha1 glycine; alpha1beta2gamma2Sgamma-aminobutyric acid (GABA)A; rho1 GABAc; 5-hydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and alpha4beta2, alpha4beta4, and alpha2beta4 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 microM) significantly enhanced alpha1 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.
Mascia
M P
MP
Consiglio Nazionale delle Ricerche, Department of Experimental Biology, Center of Neuropharmacology, University of Cagliari, Cagliari, Italy.
Maiya
R
R
Borghese
C M
CM
Lobo
I A
IA
Hara
K
K
Yamakura
T
T
Gong
D H
DH
Beckstead
M J
MJ
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins; D004347:Drug Interactions; D004553:Electric Conductivity; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018079:Receptors, GABA / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018009:Receptors, Glycine / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins; D014982:Xenopus laevis
D000079:Acetaldehyde; D050483:Dopamine Plasma Membrane Transport Proteins; D000431:Ethanol; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011950:Receptors, Cholinergic; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; C493214:SLC6A3 protein, human