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It depends on ciliary beat and ion and fluid homeostasis of the epithelium. We have shown that nicotinic ACh receptors (nAChRs) activate ion transport in mouse tracheal epithelium. Yet the receptor subtypes and signalling pathways involved remained unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Transepithelial short circuit currents (I<jats:sub>SC<\/jats:sub>) of freshly isolated mouse tracheae were recorded using the Ussing chamber technique. Changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> were studied on freshly dissociated mouse tracheal epithelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Apical application of the nAChR agonist nicotine transiently increased I<jats:sub>SC<\/jats:sub>. The nicotine effect was abolished by the nAChR antagonist mecamylamine. \u03b1\u2010Bungarotoxin (\u03b17 antagonist) had no effect. The agonists epibatidine (\u03b13\u03b22, \u03b14\u03b22, \u03b14\u03b24 and \u03b13\u03b24) and A\u201085380 (\u03b14\u03b22 and \u03b13\u03b24) increased I<jats:sub>SC<\/jats:sub>. The antagonists dihydro\u2010\u03b2\u2010erythroidine (\u03b14\u03b22, \u03b13\u03b22, \u03b14\u03b24 and \u03b13\u03b24), \u03b1\u2010conotoxin MII (\u03b13\u03b22) and \u03b1\u2010conotoxin PnIA (\u03b13\u03b22) reduced the nicotine effect. Nicotine\u2010 and epibatidine\u2010induced currents were unaltered in \u03b22<jats:sup>\u2212\/\u2212<\/jats:sup>mice, but in \u03b24<jats:sup>\u2212\/\u2212<\/jats:sup> mice no increase was observed. In the presence of thapsigargin (endoplasmatic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase inhibitor) or the ryanodine receptor antagonists JTV\u2010519 and dantrolene there was a reduction in the nicotine\u2010effect, indicating involvement of Ca<jats:sup>2+<\/jats:sup> release from intracellular stores. Additionally, the PKA inhibitor H\u201089 and the TMEM16A (Ca<jats:sup>2+<\/jats:sup>\u2010activated chloride channel) inhibitor T16Ainh\u2010A01 significantly reduced the nicotine\u2010effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>\u03b13\u03b24 nAChRs are responsible for the nicotine\u2010induced current changes via Ca<jats:sup>2+<\/jats:sup> release from intracellular stores, PKA and ryanodine receptor activation. These nAChRs might be possible targets to stimulate chloride transport via TMEM16A.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15270","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T13:19:41Z","timestamp":1600780781000},"page":"5595-5608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Nicotine stimulates ion transport via metabotropic \u03b24 subunit containing nicotinic ACh receptors"],"prefix":"10.1111","volume":"177","author":[{"given":"Praveen","family":"Kumar","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Scholze","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fronius","sequence":"additional","affiliation":[{"name":"Department of Physiology and HeartOtago, School of Biomedical Sciences University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Krasteva\u2010Christ","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika I.","family":"Hollenhorst","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,9]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","first-page":"S142","article-title":"The Concise Guide to PHARMACOLOGY 2019\/20: Ion channels","volume":"176","author":"Alexander S. 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