title: Nicotine-induced activation of soluble adenylyl cyclase participates in ion transport regulation in mouse tracheal epithelium.
abstract: OBJECTIVE
  Functional nicotinic acetylcholine receptors (nAChR) have been identified in airway epithelia and their location in the apical and basolateral membrane makes them targets for acetylcholine released from neuronal and non-neuronal sources. One function of nAChR in airway epithelia is their involvement in the regulation of transepithelial ion transport by activation of chloride and potassium channels. However, the mechanisms underlying this nicotine-induced activation of ion transport are not fully elucidated. Thus, the aim of this study was to investigate the involvement of adenylyl cyclases in the nicotine-induced ion current in mouse tracheal epithelium.
  
  
  METHODS
  To evaluate the nicotine-mediated changes of transepithelial ion transport processes electrophysiological Ussing chamber measurements were applied and nicotine-induced ion currents were recorded in the absence and presence of adenylyl cyclase inhibitors.
  
  
  RESULTS
  The ion current changes induced by nicotine (100 μM, apical) were not altered in the presence of high doses of atropine (25 μM, apical and basolateral), underlining the involvement of nAChR. Experiments with the transmembrane adenylyl cyclase inhibitor 2'5'-dideoxyadenosine (50 μM, apical and basolateral) and the soluble adenylyl cyclase inhibitor KH7 (10 μM, apical and basolateral) both reduced the nicotine-mediated ion current to a similar extent. Yet, a statistically significant reduction was obtained only in the experiments with KH7.
  
  
  CONCLUSIONS
  This study indicates that nicotine binding to nAChR in mouse tracheal epithelium activates transepithelial ion transport involving adenylyl cyclase activity. This might be important for novel therapeutic strategies targeting epithelial ion transport mediated by the non-neuronal cholinergic system.
authors: Institute of Animal Physiology, Justus-Liebig-University Giessen, Giessen, Germany.
authors: Monika I
authors: MI
authors: Hollenhorst
authors: Katrin S
authors: KS
authors: Lips
authors: Wolfgang
authors: W
authors: Kummer
authors: Martin
authors: M
authors: Fronius
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects*; D005260:Female; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D011978:Receptors, Nicotinic; D009538:Nicotine; D000262:Adenylyl Cyclases