Received for publication March 15, 2004.
Revised September 16, 2004.
Accepted for publication September 16, 2004.

Long-term exposure to nicotine modulates the level and activity of acetylcholine receptors in white blood cells of smokers and model mice

Abstract

Chronic 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 chronic administration of nicotine. The basal level of -bungarotoxin binding sites (-BGT), which correspond to the homomeric 7 nAChR subtype, was not affected in WBCs of both smokers and mice administered with nicotine. In contrast, epibatidine (EB) binding sites, which correspond to heteromeric nAChR subtypes, were detected in WBCs of smokers but not in WBCs of non-smokers. The number of EB-binding sites significantly decreased after incubation of the smokers' WBCs for three days in nicotine-free culture medium. In WBCs of wild type (WT) mice, basal level of EB binding sites was detected before nicotine administration. This basal level is reduced by ~60 percents in knockout mice lacking the genes encoding either the 2 or the 4 receptor subunits. Additional analysis of knockout mice revealed that the remaining ~40 percents do not undergo up-regulation, indicating that the 4/2 subunits comprise the up-regulated nAChRs. We further found that up-regulation 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 WBC provides a simple tool to evaluate and study tobacco addiction.

Key words: Nicotinic cholinergic, Ca imaging, Receptor binding studies

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