title: Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells.
abstract: Nicotine is a potent addictive alkaloid, and is rapidly absorbed through the alveoli of the lung. However, the transport mechanism of nicotine at the human alveolar epithelial barrier has not been investigated in great detail. In the present study, the transport mechanism of nicotine across alveolar epithelium was investigated in vitro using A549 cells, a human adenocarcinoma-derived cell line with an alveolar epithelial cell like phenotype. Nicotine uptake by A549 cells exhibited time-, temperature-, and concentration-dependence with a Km of 50.4 μM. These results suggest that a carrier-mediated transport process is involved in nicotine transport in human alveolar epithelial cells. Nicotine uptake by A549 cells was insensitive to change in extracellular pH. Moreover, nicotine uptake by A549 cells could be inhibited by organic cations such as verapamil and pyrilamine, but not typical substrates of organic cation transporters and β2-agonist. These results suggest that a novel, not yet molecularly identified, organic cation transporter plays a role in nicotine transport which is unlikely to interact with β2-agonist transport. This nicotine influx transporter in human alveolar epithelium might have implications for the rapid absorption of nicotine into the systemic circulation.
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: d1361305@ems.u-toyama.ac.jp.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Tega
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: s1060253@ems.u-toyama.ac.jp.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yuzurihara
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: kuboyosh@pha.u-toyama.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: akanumas@pha.u-toyama.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Akanuma
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Research Institute, Trinity College Dublin, Dublin 2, Ireland. Electronic address: ehrhardc@tcd.ie.
authors.forename: Carsten
authors.initials: C
authors.lastname: Ehrhardt
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: hosoyak@pha.u-toyama.ac.jp.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hosoya
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D009538:Nicotine / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011738:Pyrilamine / Q000378:metabolism; D014700:Verapamil / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D027701:Organic Cation Transport Proteins; D009538:Nicotine; D014700:Verapamil; D011738:Pyrilamine
keywords: Bronchodilator; Drug transport; Inhalation biopharmaceutics; Nicotine; Pulmonary drug disposition; Respiratory epithelium