title: Organic cation transporter function in different in vitro models of human lung epithelium.
abstract: Organic cation transporters (OCT) encoded by members of the solute carrier (SLC) 22 family of genes are involved in the disposition of physiological substrates and xenobiotics, including drugs used in the treatment of chronic obstructive lung diseases and asthma. The aim of this work was to identify continuously growing epithelial cell lines that closely mimic the organic cation transport of freshly isolated human alveolar type I-like epithelial cells (ATI) in primary culture, and which consequently, can be utilised as in vitro models for the study of organic cation transport at the air-blood barrier. OCT activity was investigated by measuring [(14)C]-tetraethylammonium (TEA) uptake into monolayers of Calu-3, NCI-H441 and A549 lung epithelial cell lines in comparison to ATI-like cell monolayers in primary culture. Levels of time-dependent TEA uptake were highest in A549 and ATI-like cells. In A549 cells, TEA uptake had a saturable and a non-saturable component with Km=528.5±373.1μM, Vmax=0.3±0.1nmol/min/mg protein and Kd=0.02μl/min/mg protein. TEA uptake into Calu-3 and NCI-H441 cells did not reach saturation within the concentration range studied. RNAi experiments in A549 cells confirmed that TEA uptake was mainly facilitated by OCT1 and OCT2. Co-incubation studies using pharmacological OCT modulators suggested that organic cation uptake pathways share several similarities between ATI-like primary cells and the NCI-H441 cell line, whereas more pronounced differences exist between primary cells and the A549 and Calu-3 cell lines.
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: Johanna J
authors: JJ
authors: Salomon
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors: Julia C
authors: JC
authors: Gausterer
authors: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Tohru
authors: T
authors: Yahara
authors: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Ken-Ichi
authors: K
authors: Hosoya
authors: Department of Cardiothoracic Surgery, Völklingen Heart Centre, Völklingen, Germany.
authors: Hanno
authors: H
authors: Huwer
authors: Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarbrücken, Germany.
authors: Marius
authors: M
authors: Hittinger
authors: Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarbrücken, Germany.
authors: Nicole
authors: N
authors: Schneider-Daum
authors: Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarbrücken, Germany.
authors: Claus-Michael
authors: CM
authors: Lehr
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. Electronic address: ehrhardc@tcd.ie.
authors: Carsten
authors: C
authors: Ehrhardt
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D027701:Organic Cation Transport Proteins / Q000378:metabolism* / Q000502:physiology; D027702:Organic Cation Transporter 1 / Q000378:metabolism / Q000502:physiology; D000075102:Organic Cation Transporter 2; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D019789:Tetraethylammonium / Q000378:metabolism
chemical_list: D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D019789:Tetraethylammonium
keywords: Lung epithelial cell lines; OCT1; OCT2; OCT3; Pulmonary drug disposition