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Research ArticleArticle

Changes in mRNA Expression Levels of Solute Carrier Transporters in Inflammatory Bowel Disease Patients

Kacper A. Wojtal, Jyrki J. Eloranta, Petr Hruz, Heike Gutmann, Jürgen Drewe, Alex Staumann, Christoph Beglinger, Michael Fried, Gerd A. Kullak-Ublick and Stephan R. Vavricka
Drug Metabolism and Disposition September 2009, 37 (9) 1871-1877; DOI: https://doi.org/10.1124/dmd.109.027367
Kacper A. Wojtal
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Jyrki J. Eloranta
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Petr Hruz
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Heike Gutmann
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Jürgen Drewe
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Alex Staumann
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Christoph Beglinger
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Michael Fried
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Gerd A. Kullak-Ublick
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Stephan R. Vavricka
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Abstract

Inflammatory bowel disease (IBD) is an inflammatory condition that affects the gastrointestinal tract. The solute carrier (SLC) superfamily of transporters 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 biopsy specimens 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 with Crohn's disease and 54 with ulcerative colitis) and 23 control subjects. mRNA expression was evaluated using the quantitative reverse transcription-polymerase chain reaction technique. We observed that in the ileum of IBD patients, mRNA levels for serotonin transporter, equilibrative nucleoside transporter (ENT) 1, ENT2, and organic anion-transporting polypeptide (OATP) 2B1 were significantly elevated, whereas levels for apical sodium-dependent bile acid transporter (ASBT) and organic zwitterion/cation transporter (OCTN) 2 were significantly lower. In colon, mRNA levels for ENT1, ENT2, concentrative nucleoside transporter (CNT) 2, OATP2B1, and OATP4A1 were significantly higher, whereas mRNA levels for OCTN2 were significantly decreased. In inflamed colon of IBD patients the mRNA expression levels of ENT1, ENT2, CNT2, OATP2B1, OATP4A1, and peptide transporter 1 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 signaling in regulation of SLC expression.

Footnotes

  • This work was supported by the Swiss National Science Foundation [Project Grants 320000-114009/1, 32-120463/1, 3347CO-108792 (Swiss IBD Cohort), and PASMA-114623]; and by the Zurich Center of Integrative Human Physiology.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.109.027367.

  • ABBREVIATIONS: SLC, solute carrier; IBD, inflammatory bowel disease; CD, Crohn's disease; UC, ulcerative colitis; PEPT, peptide transporter; TNF-α, tumor necrosis factor-α; OCTN/Octn, organic zwitterion/cation transporter; ASBT, apical sodium-dependent bile acid transporter; SERT, serotonin transporter; CNT, concentrative nucleoside transporter; OATP/Oatp, organic anion-transporting polypeptide; ENT, equilibrative nucleoside transporter; OCT, organic cation transporter; OAT, organic anion transporter; PCR, polymerase chain reaction.

  • ↵ Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

    • Accepted May 28, 2009.
    • Received March 3, 2009.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 37 (9)
Drug Metabolism and Disposition
Vol. 37, Issue 9
1 Sep 2009
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Research ArticleArticle

Changes in mRNA Expression Levels of Solute Carrier Transporters in Inflammatory Bowel Disease Patients

Kacper A. Wojtal, Jyrki J. Eloranta, Petr Hruz, Heike Gutmann, Jürgen Drewe, Alex Staumann, Christoph Beglinger, Michael Fried, Gerd A. Kullak-Ublick and Stephan R. Vavricka
Drug Metabolism and Disposition September 1, 2009, 37 (9) 1871-1877; DOI: https://doi.org/10.1124/dmd.109.027367

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Research ArticleArticle

Changes in mRNA Expression Levels of Solute Carrier Transporters in Inflammatory Bowel Disease Patients

Kacper A. Wojtal, Jyrki J. Eloranta, Petr Hruz, Heike Gutmann, Jürgen Drewe, Alex Staumann, Christoph Beglinger, Michael Fried, Gerd A. Kullak-Ublick and Stephan R. Vavricka
Drug Metabolism and Disposition September 1, 2009, 37 (9) 1871-1877; DOI: https://doi.org/10.1124/dmd.109.027367
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