Human and rodent bronchial epithelial cells express functional nicotinic acetylcholine receptors

Arno D.J. Maus, Edna F.R. Pereira, Peter I. Karachunski, Robert M. Horton, Duraiswamy Navaneetham, Kevin Macklin, Wellington S. Cortes, Edson X. Albuquerque, Bianca M. Conti-Fine

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193 Scopus citations

Abstract

We demonstrated previously that human skin keratinocytes express acetylcholine receptors (AChRs) sensitive to acetylcholine and nicotine, which regulate cell adhesion and motility. We demonstrate here that human and rodent bronchial epithelial cells (BECs) express AChRs similar to those expressed by keratinocytes and by some neurons. Patch-clamp experiments demonstrated that the BEC AChRs are functional, and they are activated by acetylcholine and nicotine. They are blocked by κ-bungarotoxin, a specific antagonist of the AChR isotypes expressed by neurons in ganglia. Their ion- gating properties are consistent with those of AChR isotypes expressed in ganglia, formed by α3, α5, and β2 or β4 subunits. Reverse transcription- polymerase chain reaction and in situ hybridization experiments demonstrated the presence in BECs of mRNA transcripts for all those AChR subunits, both in cell cultures and in tissue sections, whereas we could not detect transcripts for the α2, α4, α6, and β3 AChR subunits. The expression of α3 and α5 proteins in BEC in vivo was verified by the binding of subunit-specific antibodies to sections of trachea. Mecamylamine and κ-bungarotoxin, which are cholinergic antagonists able to block the ganglionic α3 AChRs, caused a reversible change of the cell shape of cultured, confluent human BECs. This resulted in a reduction of the area covered by the cell and in cell/cell detachment. The presence of AChRs sensitive to nicotine on the lining of the airways raises the possibility that the high concentrations of nicotine resulting from tobacco smoking will cause an abnormal activation, a desensitization, or both of the bronchial AChRs: This may mediate or facilitate some of the toxic effects of cigarette smoking in the respiratory system.

Original languageEnglish (US)
Pages (from-to)779-788
Number of pages10
JournalMolecular Pharmacology
Volume54
Issue number5
DOIs
StatePublished - Nov 1998

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