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Drug Metabolism and Disposition Fast Forward
First published on June 1, 2009; DOI: 10.1124/dmd.109.027367


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Received for publication March 3, 2009.
Revised May 28, 2009.
Accepted for publication May 28, 2009.

Changes in mRNA expression levels of solute carrier transporters in inflammatory bowel disease patients

Kacper A Wojtal 1*, Jyrki J Eloranta 1, Petr Hruz 2, Heike Gutmann 2, Juergen Drewe 2, Christoph Beglinger 1, Michael Fried 1, Gerd A Kullak-Ublick 1, Stephan R Vavricka 1

1 University Hospital Zurich 2 University Hospital Basel

* Address correspondence to: E-mail: kacper.wojtal{at}usz.ch

Abstract

Inflammatory bowel disease (IBD) is an inflammatory condition that affects gastrointestinal tract. Solute carrier superfamilly of transporters (SLC) comprise proteins involved in the uptake of drugs, hormones, and other biologically active compounds. The purpose of this study was to determine the mRNA expression levels of 15 solute carrier transporters in two regions of the intestine in IBD patients. Endoscopic biopsies were taken from two locations (terminal ileum and colon) for histological examination and RNA extraction. We quantitatively measured the mRNA expression of 15 SLC transporters in 107 IBD patients (53 Crohn's disease and 54 ulcerative colitis) and 23 control subjects. Messenger RNA expression was evaluated using the quantitative reverse transciption-PCR technique. We observed that in ileum of IBD patients, mRNA levels for SERT, ENT1, ENT2, and OATP2B1 were significantly elevated while for ASBT and OCTN2 they were significantly lower. In colon, mRNA levels for ENT1, ENT2, CNT2, OATP2B1, and OATP4A1 were significantly higher, while mRNA levels for OCTN2 were significantly decreased. In inflamed colon of IBD patients the mRNA expression levels of ENT1, ENT2, CNT2, OATP2B1, OATP4A1, and PEPT1 were significantly higher. We conclude that intestinal SLC mRNA levels are dysregulated in IBD patients, which may be linked to the inflammation of the tissue and provides an indication about the role of inflammatory signalling in regulation of SLC expression.


Key words: drug absorption, drug transport, gastrointestinal pharmacology, intestinal transport, organic anion transport, organic cation transport, transporters





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