Nicotinic cholinergic receptor expression in the human nasal mucosa.

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.

Developmental expression of nicotinic receptors in the chick and human spinal cord.

Naturally occurring programmed cell death of lumbar motor neurons in the chick spinal cord occurs between embryonic day (E) 6 and E12; whereas, a peak of motor neuron degeneration in the human spinal cord occurs between 12 and 16 weeks gestation. One of the major neurotransmitters, acetylcholine, is released from the embryonic motor neuron early in development and is thought to be responsible for early muscle activity that serves as a signal for regulating motor neuron survival. The effects of acetylcholine are mediated by two functionally distinct classes of receptors; namely, muscarinic and nicotinic with nicotinic receptors being used at the neuromuscular synapse. In this study, we determined the developmental expression profile of nicotinic acetylcholine receptor subunits in the chick and human lumbar motor neurons and skeletal muscle using reverse transcription polymerase chain reaction, immunoblots, and immunocytochemistry. Our results show that, in the chick, nicotinic receptor subunits alpha1, alpha4, alpha7, alpha8, and beta2 appear to be regulated during the process of naturally occurring motor neuron cell death in the spinal cord. A new finding was the expression of alpha8 mRNA and protein from E4.5 through E7 in chick motor neurons. Interestingly, we also found that, at E14, alpha8 protein was localized only in sensory dorsal horn neurons. In the developing human spinal cord, we determined that nicotinic receptor subunits alpha1, alpha2, alpha3, alpha4, alpha7, beta2, and beta3 were expressed before the programmed cell death period, and alpha2, alpha4, alpha7, beta2, beta3, and beta4 were expressed during the programmed cell death period. Our data demonstrate that neuronal and muscle nicotinic receptor mRNAs and proteins are expressed during important embryonic periods. This finding raises the possibility that nicotinic receptors play an important role in the spinal cord and skeletal muscle during early development.