Abstract
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. Transporters that were highly expressed in the intestine included HPT1, PEPT1, BCRP, MRP2, and MDR1, whereas, in the liver, OCT1, MRP2, OATP-C, NTCP and BSEP were the main transporters. In the kidney, OAT1 was expressed at the highest levels, followed by OAT3, OAT4, MCT5, MDR1, MRP2, OCT2, and OCTN2. The best agreement between human tissue and the representative cell line was observed for human jejunum and Caco-2 cells. Expression in liver and kidney ortholog cell lines was not correlated with that in the associated tissue. Comparisons with rat transporter gene expression revealed significant species differences. Our results allowed a comprehensive quantitative comparison of drug transporter expression in human intestine, liver, and kidney. We suggest that it would be beneficial for predictive pharmacokinetic research to focus on the most highly expressed transporters. We hope that our comparison of rat and human tissue will help to explain the observed species differences in in vivo models, increase understanding of the impact of active transport processes on pharmacokinetics and distribution, and improve the quality of predictions from animal studies to humans.
Footnotes
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↵1 The nomenclature of transporter gene families SLC and ABC has been approved and unified over recent years by the HGNC (HUGO Gene Nomenclature Committee); however, since some readers may be more familiar with earlier transporter names such as MDR1, MRP2, or OCT1, the latter terms have been used throughout the text. Please refer to Table 1 for an overview of the accustomed and official consensus gene names.
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This work was supported by grants from AstraZeneca (G.A.), Swedish research council (P.A.) and the Swedish Animal Welfare Agency (P.A.). Part of this work was presented at the BioParadigm 2005 Conference, 2005 Aug 14–18, St Gallen, Switzerland.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.107.014902.
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ABBREVIATIONS: PCR, polymerase chain reaction; RT-PCR, real-time PCR; ABC, ATP-binding cassette; SLC, solute carrier; HPT1, human peptide transporter 1.
- Received January 28, 2007.
- Accepted May 9, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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