Abstract
Alcohol and tobacco use is highly correlated in humans, and studies with animal models suggest an interaction of alcohol with neuronal nicotinic acetylcholine receptors (nAChRs). The aim of the present study was to characterize the effect of acute ethanol treatment on different combinations of human nAChR (hnAChR) subunits expressed inXenopus oocytes. Ethanol (75 mM) potentiated ACh-induced currents in α2β4, α4β4, α2β2, and α4β2 receptors. This effect was due to an increase in E max, without a change in the EC50 or Hill coefficient. hnAChR α2β4 did not develop tolerance to repeated applications of ethanol or continuous exposure (10 min). The α3β2 and α3β4combinations were insensitive to ethanol. Low concentrations of ethanol (25 and 50 mM) significantly inhibited homomeric α7receptor function, but these receptors showed highly variable responses to ethanol. These results indicate that ethanol effects on hnAChRs depend on the receptor subunit composition. In light of recent evidence indicating that nAChRs mediate and modulate synaptic transmission in the central nervous system, we postulate that acute intoxication might involve ethanol-induced alterations in the function of these receptors.
Footnotes
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Send reprint requests to: R. Adron Harris, PhD, Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway, Austin, TX 78712-1095.
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↵1 Supported by NIH Grants K01-AA00227 (C.F.V.), AA06399 (R.A.H.), AA03527 (R.A.H.).
- Abbreviations:
- nAChR
- neuronal nicotinic acetylcholine receptor
- BGT
- bungarotoxin
- GABA
- γ-aminobutyric acid
- 5-HT
- 5-hydroxytryptamine
- ACh
- acetylcholine
- Nic
- nicotine
- HEPES
- 4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid
- EtOH
- ethanol
- Received October 1, 1998.
- Accepted December 30, 1998.
- U.S. Government
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