Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells

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• 作者：Yuma Tega^a ; ¹ ; ^{d1361305@ems.u-toyama.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Chihiro Yuzurihara^a ; ¹ ; ^{s1060253@ems.u-toyama.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yoshiyuki Kubo^a ; ^{kuboyosh@pha.u-toyama.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Shin-ichi Akanuma^a ; ^{akanumas@pha.u-toyama.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Carsten Ehrhardt^b ; ^{ehrhardc@tcd.ie" class="auth_mail" title="E-mail the corresponding author} ; Ken-ichi Hosoya^a ; ^{hosoyak@pha.u-toyama.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nicotine ; Drug transport ; Respiratory epithelium ; Inhalation biopharmaceutics ; Pulmonary drug disposition ; Bronchodilator
• 刊名：Drug Metabolism and Pharmacokinetics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：31
• 期：1
• 页码：99-101
• 全文大小：304 K

文摘

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 K_m 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.