PT  - JOURNAL ARTICLE
AU  - Cormier, Anne
AU  - Paas, Yoav
AU  - Zini, Roland
AU  - Tillement, Jean-Paul
AU  - Lagrue, Gilbert
AU  - Changeux, Jean-Pierre
AU  - Grailhe, Régis
TI  - Long-Term Exposure to Nicotine Modulates the Level and Activity of Acetylcholine Receptors in White Blood Cells of Smokers and Model Mice
AID  - 10.1124/mol.104.000463
DP  - 2004 Dec 01
TA  - Molecular Pharmacology
PG  - 1712--1718
VI  - 66
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/66/6/1712.short
4100  - http://molpharm.aspetjournals.org/content/66/6/1712.full
SO  - Mol Pharmacol2004 Dec 01; 66
AB  - Long-term consumption of tobacco by smokers causes addiction and increases the level of neuronal nicotinic acetylcholine receptors (nAChRs) in the brain, a phenomenon known as up-regulation. Here, we show that up-regulation of specific nAChR subunits takes place in white blood cells (WBCs) of smokers and mice subjected to long-term administration of nicotine. The basal level of α-bungarotoxin binding site, which corresponds to the homomeric α7 nAChR subtype, was not affected in WBCs of both smokers and mice administered nicotine. In contrast, epibatidine (EB) binding sites, which correspond to heteromeric nAChR subtypes, were detected in WBCs of smokers but not in WBCs of nonsmokers. The number of EB binding sites significantly decreased after incubation of the smokers' WBCs for 3 days in nicotine-free culture medium. In WBCs of wild-type mice, basal level of EB binding sites was detected before nicotine administration. This basal level is reduced by ∼60% in knockout mice lacking the genes encoding either the β2 or the α4 receptor subunits. Additional analysis of knockout mice revealed that the remaining ∼40% do not undergo up-regulation, indicating that the α4/β2 subunits comprise the up-regulated nAChRs. We further found that upregulation in mouse WBCs is accompanied by a significant decrease in the capacity of the up-regulated receptor channels to convey calcium ions. The phenomenon of nAChR up-regulation in WBCs provides a simple tool to evaluate and study tobacco addiction.