Expression of Thirty-six Drug Transporter Genes in Human Intestine, Liver, Kidney, and Organotypic Cell Lines

@article{Hilgendorf2007ExpressionOT,
  title={Expression of Thirty-six Drug Transporter Genes in Human Intestine, Liver, Kidney, and Organotypic Cell Lines},
  author={Constanze Hilgendorf and Gustav Ahlin and Annick Seithel and Per Artursson and A. L. Ungell and Johan E. Karlsson},
  journal={Drug Metabolism and Disposition},
  year={2007},
  volume={35},
  pages={1333 - 1340}
}
This study was designed to quantitatively assess the mRNA expression of 36 important drug transporters in human jejunum, colon, liver, and kidney. Expression of these transporters in human organs was compared with expression in commonly used cell lines (Caco-2, HepG2, and Caki-1) originating from these organs to assess their value as in vitro transporter system models, and was also compared with data obtained from the literature on expression in rat tissues to assess species differences… 

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References

SHOWING 1-10 OF 42 REFERENCES

Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: comparison between human segments and Caco-2 cells.

Regional levels of drug transporters along the human intestinal tract: co-expression of ABC and SLC transporters and comparison with Caco-2 cells.

  • G. EnglundF. Rorsman P. Artursson
  • Biology
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2006

Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers.

The expression of a number of efflux protein transcripts in jejunum are equal to, or even higher than, that of MDR1, suggesting that the roles of these proteins (in particular BCRP and MRP2) in intestinal drug efflux have been underestimated.

Gene expression of CYP3A4, ABC‐transporters (MDR1 and MRP1‐MRP5) and hPXR in three different human colon carcinoma cell lines

LS180 cells were a suitable model to study MDR1 and CYP3A4 induction, but for drug transport studies Caco‐2 parental and TC‐7 cells would be preferred as the more physiological model.

Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition

A comprehensive data set of xenobiotic transporter gene expression profiles in humans and the pre-clinical species mouse, rat, beagle dog and cynomolgus monkey is generated.

MAPPING OF MULTIDRUG RESISTANCE GENE 1 AND MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN ISOFORM 1 TO 5 mRNA EXPRESSION ALONG THE HUMAN INTESTINAL TRACT

Systematic site-specific expression of MDR1 and MRP mRNA along the gastrointestinal tract in humans is shown for the first time, and all transporters showed alterations in their expression levels from the duodenum to sigmoid colon.

Variation of peptide transporter (PepT1 and HPT1) expression in Caco-2 cells as a function of cell origin.

Under identical culture conditions, Heidelberg Caco-2 cells seemed to be an appropriate in vitro cell culture model for the transport of actively transported drugs, because interpassage changes are low and the transporter distribution was homogeneous throughout the monolayer.

Comparison of Human Duodenum and Caco-2 Gene Expression Profiles for 12,000 Gene Sequences Tags and Correlation with Permeability of 26 Drugs

Gene expression profiling is a valuable new tool for investigating in vitro and in vivo permeability correlation and was consistent with observed differences in carrier mediated drug permeabilities.

FUNCTIONAL ANALYSIS OF DOG MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 (MRP2) IN COMPARISON WITH RAT MRP2

The unique transport properties of glucuronide conjugates by dog Mrp2 may lead to the species difference involving the drug-drug interaction or drug-induced hyperbilirubinemia on the bile canalicular membrane.

Gene Expression in the Human Intestine and Correlation with Oral Valacyclovir Pharmacokinetic Parameters

Correlations of pharmacokinetic parameters following oral valacyclovir or acyclovIR administration with expression levels of intestinal genes in humans are described and it is suggested that the role of HPT1 in transport of peptides and peptidomimetics drugs needs to be examined in more detail.