HUMAN AND RODENT BRONCHIAL EPITHELIAL-CELLS EXPRESS FUNCTIONAL NICOTINIC ACETYLCHOLINE-RECEPTORS

We demonstrated previously that human skin keratinocytes express acety lcholine receptors (AChRs) sensitive to acetylcholine and nicotine, wh ich regulate cell adhesion and motility. We demonstrate here that huma n and rodent bronchial epithelial cells (BECs) express AChRs similar t o those expressed by keratinocytes and by some neurons. Patch-clamp ex periments demonstrated that the BEC AChRs are functional, and they are activated by acetylcholine and nicotine. They are blocked by kappa-bu ngarotoxin, a specific antagonist of the AChR isotypes expressed by ne urons in ganglia. Their ion-gating properties are consistent with thos e of AChR isotypes expressed in ganglia, formed by alpha 3, alpha 5, a nd beta 2 or beta 4 subunits. Reverse transcription-polymerase chain r eaction and in situ hybridization experiments demonstrated the presenc e in BECs of mRNA transcripts for all those AChR subunits, both in cel l cultures and in tissue sections, whereas we could not detect transcr ipts for the alpha 2, alpha 4, alpha 6, and beta 3 AChR subunits. The expression of alpha 3 and alpha 5 proteins in BEC in vivo was verified by the binding of subunit-specific antibodies to sections of trachea. Mecamylamine and kappa-bungarotoxin, which are cholinergic antagonist s able to block the ganglionic alpha 3 AChRs, caused a reversible chan ge 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 detach ment. The presence of AChRs sensitive to nicotine on the lining of the airways raises the possibility that the high concentrations of nicoti ne 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 respi ratory system.