Victoria Hutter
Digoxin net secretory transport in bronchial epithelial cell layers is not exclusively mediated by P-glycoprotein/MDR1
Hutter, Victoria; Chau, David Y.S.; Hilgendorf, Constanze; Brown, Alan; Cooper, Anne; Zann, Vanessa; Pritchard, David I.; Bosquillon, Cynthia
Authors
David Y.S. Chau
Constanze Hilgendorf
Alan Brown
Anne Cooper
Vanessa Zann
David I. Pritchard
CYNTHIA BOSQUILLON cynthia.bosquillon@nottingham.ac.uk
Assistant Professor
Abstract
The impact of P-glycoprotein (MDR1, ABCB1) on drug disposition in the lungs as well as its presence and activity in in vitro respiratory drug absorption models remain controversial to date. Hence, we characterised MDR1 expression and the bidirectional transport of the common MDR1 probe 3H-digoxin in air-liquid interfaced (ALI) layers of normal human bronchial epithelial (NHBE) cells and of the Calu-3 bronchial epithelial cell line at different passage numbers. Madin-Darby Canine Kidney (MDCKII) cells transfected with the human MDR1 were used as positive controls. 3H-digoxin efflux ratio (ER) was low and highly variable in NHBE layers. In contrast, ER = 11.4 or 3.0 were measured in Calu-3 layers at a low or high passage number, respectively. These were, however, in contradiction with increased MDR1 protein levels observed upon passaging. Furthermore, ATP depletion and the two MDR1 inhibitory antibodies MRK16 and UIC2 had no or only a marginal impact on 3H-digoxin net secretory transport in the cell line. Our data do not support an exclusive role of MDR1 in 3H-digoxin apparent efflux in ALI Calu-3 layers and suggest the participation of an ATP-independent carrier. Identification of this transporter might provide a better understanding of drug distribution in the lungs.© 2013 The Authors. Published by Elsevier B.V. All rights reserved.
Citation
Hutter, V., Chau, D. Y., Hilgendorf, C., Brown, A., Cooper, A., Zann, V., …Bosquillon, C. (2014). Digoxin net secretory transport in bronchial epithelial cell layers is not exclusively mediated by P-glycoprotein/MDR1. European Journal of Pharmaceutics and Biopharmaceutics, 86(1), 74-82. https://doi.org/10.1016/j.ejpb.2013.06.010
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 10, 2013 |
Online Publication Date | Jun 28, 2013 |
Publication Date | 2014-01 |
Deposit Date | Nov 16, 2017 |
Journal | European Journal of Pharmaceutics and Biopharmaceutics |
Print ISSN | 0939-6411 |
Electronic ISSN | 1873-3441 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 86 |
Issue | 1 |
Pages | 74-82 |
DOI | https://doi.org/10.1016/j.ejpb.2013.06.010 |
Public URL | http://dx.doi.org/10.1016/j.ejpb.2013.06.010 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S0939641113002294 |
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