Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways

Aims: The ability to sense the bitter taste of nicotine is an important component of addiction to, and withdrawal from, cigarette smoking. alpha-Gustducin and phospholipase C-beta 2 (PLC-beta 2), molecules involved in the taste transduction pathway, have been identified in airway epithelial solitary chemosensory cells (SCCs). Airway epithelial cells also express multiple nicotinic acetylcholine receptors (nAChRs). However, the relationship between nAChRs and molecules of taste transduction in response to nicotine is not known. This study was designed to determine whether nAChRs and the taste transduction molecules alpha-gustducin, PLC-beta 2 and bitter taste receptors (T2R38) reside at sites of the intrapulmonary airways where interaction with the nicotine components of cigarette smoke is likely. Main methods: We used the reverse transcription-polymerase chain reaction (RT-PCR) to detect alpha-gustducin, PLC-beta 2 and T2R38 mRNA and immunohistochemistry to localize expression of these proteins by nAChR expressing cells of the airway. Key findings: RT-PCR demonstrated the presence of mRNA for alpha-gustducin, PLC-beta 2 and T2R38. Immunohistochemistry showed the expression of alpha-gustducin, PLC-beta 2 and T2R38 by subsets of epithelial cells at all levels of the intrapulmonary airways including bronchi, terminal and respiratory bronchioles. Double labeling demonstrated the co-expression of alpha-gustducin with alpha 3, alpha 4, alpha 5, alpha 7 and beta 2, as well as, PLC-beta 2 and T2R38 with alpha 4 alpha 5 and beta 2 nAChR subunits. Significance: These findings provide morphological evidence for the presence of molecules of the bitter taste transduction pathway in nAChR expressing SCCs of the intrapulmonary airways. These SCCs may, thus, constitute a peripheral component of the bitter taste signal transduction pathway for nicotine. (C) 2010 Elsevier Inc. All rights reserved.