ETHANOL DIFFERENTIALLY INCREASES ALPHA-2-ADRENERGIC AND MUSCARINIC ACETYLCHOLINE-RECEPTOR GENE-EXPRESSION IN NG108-15 CELLS

Modulation of alpha2-adrenergic and opioid neurotransmission may contr ibute to ethanol intoxication, tolerance, and physical dependence. We showed previously that ethanol increased the expression of functional delta-opioid receptors in NG108-15 cells (Charness, M. E., Querimit, L . A., and Diamond, 1. (1986) J. Biol. Chem. 261, 3164-3169). Here we r eport that long-term (2 days) treatment of NG108-15 cells with ethanol increased the binding of the alpha2-adrenergic receptor (alpha2AR) an tagonist [H-3]rauwolscine and the muscarinic acetylcholine receptor (m AChR) antagonist [H-3]quinuclidinyl benzilate by 2.8- and 1.4-fold, re spectively. Increased receptor expression was associated with a propor tionate increase in the potency of oxymetazoline and carbachol in inhi biting cAMP accumulation. Ethanol did not change the expression of Gal pha(i2) and reduced levels of Galpha(s). Pertussis toxin pretreatment did not prevent the ethanol-induced increase in alpha2AR, mAChR, and d elta-opioid receptor expression. Ethanol caused a large (3.6-fold), do se-dependent increase in the abundance of alpha(2B)AR mRNA (rat cDNA p robe RNG, 4.1-kb transcript). Ethanol-induced increases in alpha(2B)AR and alpha(2C)AR (rat probe RG10, 2.5-kb transcript) mRNAs were first detected after 6 h of exposure to 100 mM ethanol, became maximal after 24 h, and persisted for up to 5 days. In contrast, ethanol caused onl y a small (1.3-fold) increase in the abundance of hm4 mAChR mRNA and d id not change levels of Galpha(i2) and Galpha(s). mRNAs. Our data indi cate that clinically attainable concentrations of ethanol regulate alp ha2AR gene expression within the time frame of a single session of dri nking.