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RT-PCR experiments revealed expression of the \u03b13, \u03b14, \u03b15, \u03b17, \u03b19, \u03b110, \u03b22, and \u03b24 nAChR subunits in mouse tracheal epithelium. In Ussing chamber recordings of mouse tracheae, apically applied nicotine (100 \u03bcM) induced a dose-dependent increase of the transepithelial short-circuit current (EC50: 14.6 \u03bcM). The nicotine-induced effect (INIC) was attenuated by mecamylamine (25 \u03bcM, apical) and methyllycaconitine (1 \u03bcM, apical). The nAChR agonist 1.1-dimethyl-4-phenylpiperatinium iodide (DMPP) (100 \u03bcM) revealed apical and basolateral location of the receptors. INIC was not affected by the sodium channel inhibitor amiloride (10 \u03bcM, apical) or the cystic fibrosis transmembrane conductance regulator inhibitor CFTRinh-172 (20 \u03bcM, apical) but was reduced by the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 \u03bcM, apical), the Na+\/K+\/2Cl\u2212 cotransporter inhibitor bumetanide (200 \u03bcM, basolateral), the potassium channel inhibitor Ba2+ (5 mM, basolateral), and 4.4\u2032-diisothiocyanatostilbene-2.2\u2032-disulfonate (100 \u03bcM, apical), indicating a contribution of Ca2+\u2013activated chloride channels and potassium channels. Removal of extracellular Na+ (apical) or Ca2+ (apical) did not influence INIC but reduced the DMPP effect. Experiments with the Ca2+\u2013ionophore A23187, a mix of 3-isobutyl-1-methylxanthine and forskolin, or the inositol-1,4,5-triphospate (IP3) receptor inhibitor 2-aminoethyl-diphenyl-borinate (75 \u03bcM, apical) decreased INIC, indicating a nicotine-mediated increase of intracellular Ca2+ and cAMP levels involving the IP3 signaling pathway. These findings indicate the activity of Ca2+\u2013permeable nAChRs and alternative metabotropic pathways by nAChR activation that mediate Cl\u2013 and K+ transport in tracheal epithelium.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0171oc","type":"journal-article","created":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T23:47:33Z","timestamp":1313711253000},"page":"106-114","source":"Crossref","is-referenced-by-count":21,"title":["Evidence for Functional Atypical Nicotinic Receptors That Activate K+\u2013Dependent Cl\u2212 Secretion in Mouse Tracheal Epithelium"],"prefix":"10.1093","volume":"46","author":[{"given":"Monika I.","family":"Hollenhorst","sequence":"first","affiliation":[{"name":"Institute of Animal Physiology, Justus-Liebig-University Giessen, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin S.","family":"Lips","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 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