Changes in mRNA expression levels of solute carrier transporters in inflammatory bowel disease patients
Wojtal, K A; Eloranta, J J; Hruz, P; Gutmann, H; Drewe, J; Beglinger, C; Fried, M; Kullak-Ublick, G A; Vavricka, S R (2009). Changes in mRNA expression levels of solute carrier transporters in inflammatory bowel disease patients. Drug Metabolism and Disposition, 37(9):1871-1877.
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.
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04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
04 Faculty of Medicine > Center for Integrative Human Physiology
American Society for Pharmacology and Experimental Therapeutics
Drug Metab Dispos - free full text
https://doi.org/10.1124/dmd.109.027367
Wojtal, K A Eloranta, J J Hruz, P Gutmann, H Drewe, J Beglinger, C Fried, M Kullak-Ublick, G A Vavricka, S R