Cough sensors. IV. Nicotinic membrane receptors on cough sensors

Cigarette smoke is undoubtedly one of the most common inhaled irritants in the human respiratory tract, and invariably evokes coughing in both smokers and nonsmokers. Results obtained from the studies in human volunteers and from single-fiber recording of vagal bronchopulmonary afferents in animals clearly indicate that nicotine is primarily responsible for the airway irritation and coughing caused by inhalation of cigarette smoke. Furthermore, both nicotine and acetylcholine can evoke inward current, membrane depolarization, and action potentials in isolated pulmonary sensory neurons, and these responses are blocked by hexamethonium. Taken together, these findings suggest that the tussive effect of nicotine is probably mediated through an activation of nicotinic acetylcholine receptors (nAChRs) expressed on the sensory terminals of cough receptors located in the airway mucosa. Indeed, the expressions of α4 - α7 and β2 - β4 subunits of nAChR transcripts in pulmonary sensory neurons have lent further support to this conclusion. The specific subtypes of the neuronal nAChRs and their subunit compositions expressed on the cough sensors remain to be determined.