Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer

摘要: Forty-eight million Americans smoke because of addiction to nicotine, and prevention smoking initiation new methods for aiding in cessation are some the most important opportunities disease available (1). This results from nicotine acting on neuronal nicotinic acetylcholine receptors (nAchRs) brain key regions controlling behavior. There is detailed structural functional information nAchRs that prototype ligand-gated ion channels mediating transmission endogenous (Ach) exogenous signals central peripheral nervous system (2). In addition well-formulated role etiology addiction, emerging evidence suggests contributes directly lung carcinogenesis through stimulation non-neuronal cells. Our group showed many cancers expressed low concentrations blocked induction apoptosis these cells (3). Conti-Fine’s demonstrated human rodent bronchial epithelial (4, 5). While not epithelium, Grando colleagues epidermal keratinocytes synthesize, secrete, degrade Ach which used mediate calcium influx cell differentiation α7 same (6, 7). bind only but also nicotine-derived nitrosamines such as tobacco specific carcinogens N′-Nitrosonornicotine (NNN) 4(methylnitrosamino)-1-(3–pyridyl)-1-butanone (NNK), potent carcinogens. Schuller’s cancer fetal pulmonary neuroendocrine express ligands with higher affinity than stimulating growth (8–10).