Organic cation transporter function in different in vitro models of human lung epithelium.

2.50
Hdl Handle:
http://hdl.handle.net/10033/582803
Title:
Organic cation transporter function in different in vitro models of human lung epithelium.
Authors:
Salomon, Johanna J; Gausterer, Julia C; Yahara, Tohru; Hosoya, Ken-Ichi; Huwer, Hanno; Hittinger, Marius; Schneider-Daum, Nicole; Lehr, Claus-Michael; Ehrhardt, Carsten
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.
Affiliation:
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
Citation:
Organic cation transporter function in different in vitro models of human lung epithelium. 2015, 80:82-8 Eur J Pharm Sci
Journal:
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Issue Date:
1-Dec-2015
URI:
http://hdl.handle.net/10033/582803
DOI:
10.1016/j.ejps.2015.08.007
PubMed ID:
26296865
Type:
Article
Language:
en
ISSN:
1879-0720
Appears in Collections:
publications of the department drug delivery ([TC] DDEL)

Full metadata record

DC FieldValue Language
dc.contributor.authorSalomon, Johanna Jen
dc.contributor.authorGausterer, Julia Cen
dc.contributor.authorYahara, Tohruen
dc.contributor.authorHosoya, Ken-Ichien
dc.contributor.authorHuwer, Hannoen
dc.contributor.authorHittinger, Mariusen
dc.contributor.authorSchneider-Daum, Nicoleen
dc.contributor.authorLehr, Claus-Michaelen
dc.contributor.authorEhrhardt, Carstenen
dc.date.accessioned2015-11-27T14:45:46Zen
dc.date.available2015-11-27T14:45:46Zen
dc.date.issued2015-12-01en
dc.identifier.citationOrganic cation transporter function in different in vitro models of human lung epithelium. 2015, 80:82-8 Eur J Pharm Scien
dc.identifier.issn1879-0720en
dc.identifier.pmid26296865en
dc.identifier.doi10.1016/j.ejps.2015.08.007en
dc.identifier.urihttp://hdl.handle.net/10033/582803en
dc.description.abstractOrganic 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.en
dc.language.isoenen
dc.titleOrganic cation transporter function in different in vitro models of human lung epithelium.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.en
dc.identifier.journalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciencesen

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