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

Hayeshi, Rose (author)
Hilgendorf, Constanze (author)
Artursson, Per (author)
Uppsala universitet,Institutionen för farmaci
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Augustijns, Patrick (author)
Brodin, Birger (author)
Dehertogh, Pascale (author)
Fisher, Karen (author)
Fossati, Lina (author)
Hovenkamp, Egbert (author)
Korjamo, Timo (author)
Masungi, Chantal (author)
Maubon, Nathalie (author)
Mols, Raf (author)
Müllertz, Anette (author)
Mönkkönen, Jukka (author)
O'Driscoll, Caitriona (author)
Oppers-Tiemissen, H M (author)
Ragnarsson, Eva G E (author)
Uppsala universitet,Institutionen för farmaci
Rooseboom, Martijn (author)
Ungell, Anna-Lena (author)
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 (creator_code:org_t)
Elsevier BV, 2008
2008
English.
In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 35:5, s. 383-396
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 thus be due to differences in transporter expression as shown for PepT1 and MDR1 which in turn is determined by the culture conditions. Absolute expression of genes was variable indicating that small differences in culture conditions have a significant impact on gene expression, although the overall expression patterns were similar.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

Caco-2 cells
Active transport
ABC-transport
SLC-transport
Drug transport protein expression
Drug transport protein function
PHARMACY
FARMACI

Publication and Content Type

ref (subject category)
art (subject category)

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