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Open AccessArticle

OCTN2-Mediated Acetyl-l-Carnitine Transport in Human Pulmonary Epithelial Cells In Vitro

1
Department of Translational Pulmonology, Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, 69120 Heidelberg, Germany
2
School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
3
Clinical Pharmacy Department, Faculty of Pharmacy, University of Kufa, Al-Najaf 31001, Iraq
4
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
5
Department of Cardiothoracic Surgery, Völklingen Heart Centre, 66333 Völklingen, Germany
6
Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, 66123 Saarbrücken, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 396; https://doi.org/10.3390/pharmaceutics11080396
Received: 28 June 2019 / Revised: 31 July 2019 / Accepted: 6 August 2019 / Published: 7 August 2019
(This article belongs to the Special Issue Advances in Pulmonary Drug Delivery)
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Abstract

The carnitine transporter OCTN2 is associated with asthma and other inflammatory diseases. The aims of this work were (i) to determine carnitine uptake into freshly isolated human alveolar type I (ATI)-like epithelial cells in primary culture, (ii) to compare the kinetics of carnitine uptake between respiratory epithelial in vitro cell models, and (iii) to establish whether any cell line was a suitable model for studies of carnitine transport at the air-blood barrier. Levels of time-dependent [3H]-acetyl-l-carnitine uptake were similar in ATI-like, NCl-H441, and Calu-3 epithelial cells, whereas uptake into A549 cells was ~5 times higher. Uptake inhibition was more pronounced by OCTN2 modulators, such as l-Carnitine and verapamil, in ATI-like primary epithelial cells compared to NCl-H441 and Calu-3 epithelial cells. Our findings suggest that OCTN2 is involved in the cellular uptake of acetyl-l-carnitine at the alveolar epithelium and that none of the tested cell lines are optimal surrogates for primary cells. View Full-Text
Keywords: organic cation transporter; OCTN2; lung epithelium; acetyl-l-carnitine; epithelial transport; asthma; in vitro models organic cation transporter; OCTN2; lung epithelium; acetyl-l-carnitine; epithelial transport; asthma; in vitro models
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MDPI and ACS Style

Salomon, J.J.; Gausterer, J.C.; Selo, M.A.; Hosoya, K.-I.; Huwer, H.; Schneider-Daum, N.; Lehr, C.-M.; Ehrhardt, C. OCTN2-Mediated Acetyl-l-Carnitine Transport in Human Pulmonary Epithelial Cells In Vitro. Pharmaceutics 2019, 11, 396.

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