Nicotinic Cholinergic Receptor Expression in the Human Nasal Mucosa

Abstract

Twenty-four nasal mucosa specimens were obtained from the inferior or middle turbinates of 6 normal subjects and 18 patients with chronic sinusitis, inflammatory polyp formation, or sinus allergies. Reverse transcription-polymerase chain reaction analysis was used to identify the non-neuronal nicotinic cholinergic receptor (nAChR) subunits that were expressed in the nasal mucosa. Collectively, transcripts for alpha (alpha1, alpha2, alpha3, alpha4, alpha6, alpha7) and beta (beta2, beta3, beta4) nAChR subunit genes were detected in the respiratory mucosa. The alpha3, alpha7, and beta2 subunits were expressed in 92%, 88%, and 75% of the subjects, respectively. There was a high degree of interindividual variation in nAChR subunit gene expression among subjects. A significant univariate association was found between tissue type and beta4 expression and between gender and beta3 expression. These data suggest that cells in the nasal mucosa express the necessary messenger RNAs (mRNAs) for numerous nAChR combinations. Moreover, our identification of nAChR subunit mRNAs in the nasal mucosa extends the findings of other functional studies of nAChRs in nasal epithelial cells and implies that nicotine from tobacco products such as cigarette smoke and nicotine nasal spray may have direct cellular effects on nasal mucosa cells through activation of homogeneous or heterogeneous nAChRs. A significant number of patients receiving nicotine nasal spray have reported nasal irritation, and there are reports of transient irritation of the throat and trachea with the use of smoke-free nicotine cigarettes. These adverse respiratory effects may be due to activation of nAChRs in epithelial cells of the nose and trachea.

The airway sensory impact of nicotine contributes to the conditioned reinforcing effects of individual puffs from cigarettes

“…One explanation for this may be that, unlike nicotine's pharmacologic effects, nicotine's airway sensory effects are not mediated by nicotinic acetylcholine receptors; rapid desensitization of nicotinic acetylcholine receptors may underlie acute tolerance, so a nonreceptor-mediated process could potentially circumvent acute tolerance. This is unlikely, however, since the airway expresses an abundance of nicotinic acetylcholine receptors (Wang et al, 2001;Keiger et al, 2003;Proskocil et al, 2004) and it has been shown that blockade of nicotinic acetylcholine receptors significantly reduces the airway sensory effects of smoking (Lee et al, 1993;Rose et al, 1999a,b). An alternative explanation is that the airway sensations stimulated by nicotine may be transduced by an isoform of the nicotinic acetylcholine receptor that is not susceptible to rapid desensitization, or does not undergo as complete a desensitization as the receptors that mediate nicotine's pharmacologic effects.…”

Sinonasal inflammation in COPD: a systematic review: Table 1–

“…Nicotine receptor gene expression in the nasal mucosa has been demonstrated [38], and perhaps nicotine receptor activation somehow influences the mucosal compliance. One study found that smoking cessation in patients with chronic rhinitis did not improve the minimal cross-sectional area after 20 weeks when smoking was substituted with nasal nicotine; unfortunately, no controls were enrolled [39].…”

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

“…Finally, other nAChR subtypes may underlie behavioral sex differences. For example, a study found sex differences in b 3 -nAChR expression in the nasal mucosa of human subjects (48). Future studies are needed to evaluate these alternatives.…”