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Cited by 263Drug Transport and Resistance MechanismsPharmacogenetics and Drug MetabolismDrug Solubulity and Delivery Systems

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Comparison of drug transporter gene expression and functionality in Caco-2 cells from 10 different laboratories

Hayeshi, Rose, Hilgendorf, Constanze, Artursson, Per, Augustijns, Patrick, Brodin, Birger, Dehertogh, Pascale, Fisher, Karen, Fossati, Lina, Hovenkamp, Egbert, Korjamo, Timo, Masungi, Chantal, Maubon, Nathalie, Mols, Raf, Müllertz, Anette, Mönkkönen, Jukka, O’Driscoll, Caitriona, Oppers-Tiemissen, H.M., Ragnarsson, Eva G.E., Rooseboom, Martijn, Ungell, Anna-Lena·2008·European Journal of Pharmaceutical Sciences
DOI 10.1016/j.ejps.2008.08.004
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Abstract

Caco-2 cells, widely used to study carrier mediated uptake and efflux mechanisms, are known to have different properties when cultured under different conditions. In this study, Caco-2 cells from 10 different laboratories were compared in terms of mRNA expression levels of 72 drug and nutrient transporters, and 17 other target genes, including drug metabolising enzymes, using real-time PCR. The rank order of the top five expressed genes was: HPT1>GLUT3>GLUT5>GST1A>OATP-B. Rank correlation showed that for most of the samples, the gene ranking was not significantly different. Functionality of transporters and the permeability of passive transport markers metoprolol (transcellular) and atenolol (paracellular) were also compared. MDR1 and PepT1 function was investigated using talinolol and Gly-Sar transport, respectively. Sulfobromophthalein (BSP) was used as a marker for MRP2 and OATP-B functionality. Atenolol permeability was more variable across laboratories than metoprolol permeability. Talinolol efflux was observed by all the laboratories, whereas only five laboratories observed significant apical uptake of Gly-Sar. Three laboratories observed significant efflux of BSP. MDR1 expression significantly correlated to the efflux ratio and net active efflux of talinolol. PepT1 mRNA levels showed significant correlation to the uptake ratio and net active uptake of Gly-Sar. MRP2 and OATP-B showed no correlation to BSP transport parameters. Heterogeneity in transporter activity may t…

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Metadata

Authors
Hayeshi, R., Hilgendorf, C., Artursson, P., Augustijns, P., Brodin, B., Dehertogh, P., Fisher, K., Fossati, L., Hovenkamp, E., Korjamo, T., Masungi, C., Maubon, N., Mols, R., Müllertz, A., Mönkkönen, J., O’Driscoll, C., Oppers-Tiemissen, H. M., Ragnarsson, E. G. E., Rooseboom, M., & Ungell, A.-L.
Affiliations
  • AstraZeneca (Sweden) (SE)
  • Uppsala University (SE)
  • KU Leuven (BE)
  • University of Copenhagen (DK)
  • University College Cork (IE)
  • Solvay (France) (FR)
  • University of Eastern Finland (FI)
  • Organon (Netherlands) (NL)
Corresponding author
Hayeshi, Rose
ORCID
Venue
European Journal of Pharmaceutical Sciences
Publisher
Elsevier BV
Published
2008-12
Volume
35
Issue
5
Pages
383-396
ISSN
0928-0987 (ISSN-L)
DOI
10.1016/j.ejps.2008.08.004
OpenAlex
W2023648745
Cited by
263
References
42
Citations by year
2026: 4 · 2025: 7 · 2024: 10 · 2023: 9 · 2022: 14 · 2021: 16 · 2020: 13 · 2019: 18 · 2018: 13 · 2017: 14 · 2016: 13 · 2015: 22 · 2014: 13 · 2013: 19 · 2012: 25
FWCI
9.15
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Journal of Pharmaceutical Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • Lirias (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
Caco-2 cells, inter-laboratory variability, culture conditions, MDR1, P-glycoprotein, PepT1, MRP2, drug efflux, drug uptake, sulfobromophthalein, talinolol, GLUT3, GLUT5, drug-metabolizing enzymes, intestinal permeability
MeSH terms
Carrier Proteins, Data Interpretation, Statistical, Pharmaceutical Preparations, Genetic Markers, Humans, Laboratories, Permeability, RNA, Messenger, Reproducibility of Results, Gene Expression, DNA, Complementary, Caco-2 Cells, Radiopharmaceuticals, Reverse Transcriptase Polymerase Chain Reaction

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