Airway irritation and cough evoked by inhaled cigarette smoke: Role of neuronal nicotinic acetylcholine receptors

L. Y. Lee, N. K. Burki, D. C. Gerhardstein, Q. Gu, Y. R. Kou, J. Xu

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


In a series of studies carried out in different experimental models, we investigated the type(s) of lung afferents and mechanism(s) underlying the cigarette smoke-induced airway irritation and cough. In healthy non-smokers, the intensity of airway irritation and cough evoked by cigarette smoke was markedly reduced after premedication with hexamethonium. A similar pattern of responses was also triggered by inhalation of nicotine aerosol. These studies in human subjects suggested nicotine as the primary causative agent in cigarette smoke that evokes airway irritation. Indeed, single-fiber recording experiments performed in anesthetized dogs showed that both C-fibers and rapidly adapting receptors in the lungs and airways were stimulated by inhalation of one puff of cigarette smoke, and the intensity of this stimulatory effect was related to the nicotine content in the cigarette and abolished by hexamethonium. To further study the direct effect of nicotine on these sensory nerves, we measured the change in intracellular calcium concentration ([Ca2+]i) of pulmonary sensory neurons isolated from the nodose and jugular ganglia of adult rats. Our results showed that nicotine evoked an abrupt and transient increase in [Ca2+]i in ∼34% of the 522 neurons tested, and 1,1-dimethyl-4-phenylpiperazinium, a selective agonist of the neuronal nicotinic acetylcholine receptors (NnAChRs), evoked a similar pattern of response as that of nicotine in these neurons. In conclusion, results of these studies show that nicotine exerts a direct stimulatory effect on vagal pulmonary sensory neurons. This stimulatory effect of nicotine is primarily responsible for the airway irritation and cough evoked by inhaled cigarette smoke, and is mediated through an activation of the NnAChRs.

Original languageEnglish
Pages (from-to)355-364
Number of pages10
JournalPulmonary Pharmacology and Therapeutics
Issue number4
StatePublished - Aug 2007

Bibliographical note

Funding Information:
The authors thank Wen-Bin Young, Alan Wang, Robert Morton and Michelle Wiggers for their technical assistances in these studies. These studies were supported in part by grants from the National Institutes of Health (HL-40369 and HL-67379).


  • Airway irritation
  • Airway receptors
  • Airway reflexes
  • Cough
  • Tobacco

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)


Dive into the research topics of 'Airway irritation and cough evoked by inhaled cigarette smoke: Role of neuronal nicotinic acetylcholine receptors'. Together they form a unique fingerprint.

Cite this