Effects of ethanol on recombinant human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.
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 in Xenopus oocytes. Ethanol (75 mM) potentiated ACh-induced currents in alpha2beta4, alpha4beta4, alpha2beta2, and alpha4beta2 receptors. This effect was due to an increase in Emax, without a change in the EC50 or Hill coefficient. hnAChR alpha2beta4 did not develop tolerance to repeated applications of ethanol or continuous exposure (10 min). The alpha3beta2 and alpha3beta4 combinations were insensitive to ethanol. Low concentrations of ethanol (25 and 50 mM) significantly inhibited homomeric alpha7 receptor 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.
Cardoso
R A
RA
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
Brozowski
S J
SJ
Chavez-Noriega
L E
LE
Harpold
M
M
Valenzuela
C F
CF
Harris
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D014982:Xenopus laevis
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D000431:Ethanol; D009538:Nicotine; D000109:Acetylcholine