Ra. Cardoso et al., Effects of ethanol on recombinant human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes, J PHARM EXP, 289(2), 1999, pp. 774-780
Citations number
35
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Alcohol and tobacco use is highly correlated in humans, and studies with an
imal models suggest an interaction of alcohol with neuronal nicotinic acety
lcholine receptors (nAChRs), The aim of the present study was to characteri
ze the effect of acute ethanol treatment on different combinations of human
nAChR (hnAChR) subunits expressed in Xenopus oocytes. Ethanol (75 mM) pote
ntiated ACh-induced currents in alpha(2)beta(4), alpha(4)beta(4), alpha(2)b
eta(2), and alpha(4)beta(2) receptors. This effect was due to an increase i
n E-max, without a change in the EC50 or Hill coefficient. hnAChR alpha(2)b
eta(4) did not develop tolerance to repeated applications of ethanol or con
tinuous exposure (10 min). The alpha(3)beta(2) and alpha(3)beta(4) combinat
ions were insensitive to ethanol. Low concentrations of ethanol (25 and 50
mM) significantly inhibited homomeric alpha(7) receptor function, but these
receptors showed highly variable responses to ethanol. These results indic
ate that ethanol effects on hnAChRs depend on the receptor subunit composit
ion. In light of recent evidence indicating that nAChRs mediate and modulat
e synaptic transmission in the central nervous system, we postulate that ac
ute intoxication might involve ethanol-induced alterations in the function
of these receptors.