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Chronic Ethanol Treatment Decreases [ 3 H]Epibatidine and [ 3 H]Nicotine Binding and Differentially Regulates mRNA Levels of Nicotinic Acetylcholine Receptor Subunits Expressed in M10 and SH‐SY5Y Neuroblastoma Cells
Author(s) -
Gorbounova Olga,
Svensson AnneLie,
Jönsson Patrik,
Mousavi Malahat,
Miao Hui,
HellströmLindahl Eva,
Nordberg Agneta
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70031134.x
Subject(s) - epibatidine , nicotine , acetylcholine receptor , nicotinic agonist , nicotinic acetylcholine receptor , chemistry , alpha 4 beta 2 nicotinic receptor , messenger rna , acetylcholine , receptor , ethanol , sh sy5y , endocrinology , medicine , biology , biochemistry , cell culture , genetics , gene , neuroblastoma
For a study of the underlying mechanisms of a possible interaction between ethanol and nicotinic receptors during ethanol dependence, the aim of this work was to investigate the effect of chronic ethanol exposure on nicotinic receptor subtypes in a transfected fibroblast cell line (M10 cells) stably expressing α4β2 nicotinic receptor subtype and an SH‐SY5Y neuroblastoma cell line expressing α3, α5, α7, β2, and β4 nicotinic acetylcholine receptor (nAChR) subunits. A significant dose‐related decrease (−30–80%) in number of [ 3 H]nicotine binding sites was observed in ethanol‐treated (25–240 m M ) compared with untreated M10 cells. Similarly, 4‐day treatment with ethanol in concentrations relevant to chronic alcoholism (100 m M ) decreased the number of nicotinic receptor binding sites in the SH‐SY5Y cells when measured using [ 3 H]epibatidine. When M10 cells were chronically treated with nicotine, ethanol partly inhibited the up‐regulation of nicotinic receptors when present in the cells together with nicotine. Chronic treatment for 4 days with 100 m M ethanol significantly decreased the mRNA level for the α3 nAChR subunit (−39%), while the mRNA levels for the α7 (+30%) and α4 (+22%) subunits were significantly increased. Chronic ethanol treatment did not affect the mRNA levels for the β2 nAChR subunit. Changes in the levels of nAChR protein and mRNA may have adaptive significance and be involved in the development of dependence, tolerance, and addiction to chronic ethanol and nicotine exposure. They also may be targets for therapeutic strategies in the treatment of ethanol and nicotine dependence.