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Organic cation transporter function in different in vitro models of human lung epithelium.
Salomon, Johanna J Gausterer, Julia C Yahara, Tohru Hosoya, Ken-Ichi Huwer, Hanno Hittinger, Marius Schneider-Daum, Nicole Lehr, Claus-Michael Ehrhardt, Carsten
Salomon, Johanna J
Gausterer, Julia C
Yahara, Tohru
Hosoya, Ken-Ichi
Huwer, Hanno
Hittinger, Marius
Schneider-Daum, Nicole
Lehr, Claus-Michael
Ehrhardt, Carsten
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2015-12-01
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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.
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Organic cation transporter function in different in vitro models of human lung epithelium. 2015, 80:82-8 Eur J Pharm Sci
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en
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1879-0720