Regional Expression Levels of Drug Transporters and Metabolizing Enzymes along the Pig and Human Intestinal Tract and Comparison with Caco-2 Cells

Authors Stefan Vaessen , M.M.H. van Lipzig , Raymond Pieters , Cyrille Krul , Heleen Wortelboer , E. van de Steeg
Published in Drug Metabolism and Disposition
Publication date 2017
Research groups Innovative Testing in Life Sciences and Chemistry
Type Article

Summary

From TU Delft repository: "Intestinal transporter proteins and metabolizing enzymes play a crucial role in the oral absorption of a wide variety of drugs. The aim of the current study was to characterize better available intestinal in vitro models by comparing expression levels of these proteins and enzymes between porcine intestine, human intestine, and Caco-2 cells. We therefore determined the absolute protein expression of 19 drug transporters and the mRNA expression of 12 metabolic enzymes along the pig intestinal tract (duodenum, jejunum, ileum; N = 4), in human intestine (jejunum; N = 9), and Caco-2 cells. Expression of the included transporters and enzymes was in general well comparable between porcine and human intestinal tissue, although breast cancer resistance protein, monocarboxylate transporter 5, multidrug resistance protein (MRP) 1,MRP1,MRP3 (∼2-fold), and organic anion-transporting polypeptide (OATP) 4A1 (∼6-fold) was higher expressed in pig compared with human jejunum. Alternatively, expression level of relevant transporter proteins (glucose transporter 1, OATP4A1, MRP2, MRP1, and OATP2B1) was significantly higher (3- to 130-fold) in Caco-2 cells compared with human jejunum. Moreover, all examined CYPs showed at least a fivefold lower gene expression in Caco-2 cells compared with human jejunum, with the smallest differences for CYP1A1 and CYP3A5 and the largest difference for CYP3A4 (871-fold higher expression in human jejunum compared with Caco-2 cells). In conclusion, a comprehensive overview is provided of the expression levels of clinically relevant transporter proteins and metabolic enzymes in porcine and human intestinal tissue and Caco-2 cells, which may assist in deciding upon the most suitable model to further improve our understanding of processes that determine intestinal absorption of compounds." https://repository.tudelft.nl/view/tno/uuid%3A48bafffb-6f20-4569-a343-7edf003ca058

researchcomponents.publicationcontent.personslist.publicationauthors

  • Raymond Pieters | Professor | Research group Innovative Testing in Life Sciences & Chemistry
    Raymond Pieters
    • Professor
    • Research groups: Innovative Testing in Life Sciences and Chemistry
  • Cyrille Krul
    Cyrille Krul
    • Professor
    • Research groups: Innovative Testing in Life Sciences and Chemistry

Language English
Published in Drug Metabolism and Disposition
Year and volume 4 45
ISBN/ISSN URN:ISSN:1521-009X
Key words Biology, Food and Nutrition
Page range 353-360

Innovative Testing in Life Sciences and Chemistry