ArticleBritish journal of pharmacology2010
Differences in the expression of endogenous efflux transporters in MDR1-transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 104 citations in OpenAlex.
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- Generation of Knockout and Transgenic Zebrafish to Characterize Abcc4 Functions in Detoxification and Efflux of Lead.International journal of molecular sciences · 2021Article
- Disruption of small molecule transporter systems by Transporter-Interfering Chemicals (TICs).FEBS letters · 2020Review
- A face-to-face comparison of claudin-5 transduced human brain endothelial (hCMEC/D3) cells with porcine brain endothelial cells as blood-brain barrier models for drug transport studies.Fluids and barriers of the CNS · 2020Article
- IPEC-J2 rMdr1a, a New Cell Line with Functional Expression of Rat P-glycoprotein Encoded by Rat Mdr1a for Drug Screening Purposes.Pharmaceutics · 2020Article
- ABC Transporters at the Blood-Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas.Pharmaceutics · 2019Review
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- Intracellular drug bioavailability: a new predictor of system dependent drug disposition.Scientific reports · 2017Article
- Liver and Kidney on Chips: Microphysiological Models to Understand Transporter Function.Clinical pharmacology and therapeutics · 2016Review
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- Atenolol Renal Secretion Is Mediated by Human Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Proteins.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations.Scientific reports · 2015Article
- Genomic Knockout of Endogenous Canine P-Glycoprotein in Wild-Type, Human P-Glycoprotein and Human BCRP Transfected MDCKII Cell Lines by Zinc Finger Nucleases.Pharmaceutical research · 2015Article
- Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model.Pharmacology research & perspectives · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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Abstract
background and purposeP-glycoprotein (Pgp) efflux assays are widely used to identify Pgp substrates. The kidney cell lines Madin-Darby canine kidney (MDCK)-II and LLC-PK1, transfected with human MDR1 (ABCB1) are used to provide recombinant models of drug transport. Endogenous transporters in these cells may contribute to the activities of recombinant transporters, so that drug transport in MDR1-transfected cells is often corrected for the transport obtained in parental (wildtype) cells. However, expression of endogenous transporters may vary between transfected and wildtype cells, so that this correction may cause erroneous data. Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK-II or LLC cells and the consequences for Pgp-mediated drug transport. EXPERIMENTAL APPROACH: Using quantitative real-time RT-PCR, we determined the expression of endogenous Mdr1 mRNA and other efflux transporters in wildtype and MDR1-transfected MDCK-II and LLC cells. Transcellular transport was measured with the test substrate vinblastine. KEY
resultsIn MDR1-transfected MDCK cells, expression of endogenous (canine) Mdr1 and Mrp2 (Abcc2) mRNA was markedly lower than in wildtype cells, whereas MDR1-transfected LLC cells exhibited comparable Mdr1 but strikingly higher Mrp2 mRNA levels than wildtype cells. As a consequence, transport of vinblastine by human Pgp in efflux experiments was markedly underestimated when transport in MDR1-transfected MDCK cells was corrected for transport obtained in wildtype cells. This problem did not occur in LLC cells. CONCLUSIONS AND IMPLICATIONS: Differences in the expression of endogenous efflux transporters between transfected and wildtype MDCK cells provide a potential bias for in vitro studies on Pgp-mediated drug transport.
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