title: Human and rodent bronchial epithelial cells express functional nicotinic acetylcholine receptors.
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 kappa-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 alpha3, alpha5, and beta2 or beta4 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 alpha2, alpha4, alpha6, and beta3 AChR subunits. The expression of alpha3 and alpha5 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 antagonists able to block the ganglionic alpha3 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.
authors.affiliation: Department of Biochemistry, University of Minnesota, St. Paul, Minnesota 55108, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Maus
authors.forename: E F
authors.initials: EF
authors.lastname: Pereira
authors.forename: P I
authors.initials: PI
authors.lastname: Karachunski
authors.forename: R M
authors.initials: RM
authors.lastname: Horton
authors.forename: D
authors.initials: D
authors.lastname: Navaneetham
authors.forename: K
authors.initials: K
authors.lastname: Macklin
authors.forename: W S
authors.initials: WS
authors.lastname: Cortes
authors.forename: E X
authors.initials: EX
authors.lastname: Albuquerque
authors.forename: B M
authors.initials: BM
authors.lastname: Conti-Fine
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure*; D002448:Cell Adhesion / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013045:Species Specificity; D014132:Trachea / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D014316:Tritium
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D018680:Cholinergic Antagonists; D018722:Nicotinic Agonists; D011725:Pyridines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014316:Tritium; D009538:Nicotine; C082748:epibatidine