Abstract
Intestinal absorption of drugs, nutrients, and other compounds is mediated by uptake transporters expressed at the apical enterocyte membrane. These compounds are returned to the intestinal lumen or released into portal circulation by intestinal efflux transporters expressed at apical or basolateral membranes, respectively. One important transporter superfamily, multiple members of which are intestinally expressed, are the solute carriers (SLCs). SLC expression levels may determine the pharmacokinetics of drugs that are substrates of these transporters. In this study we characterize the distribution of 15 human SLC transporter mRNAs in histologically normal biopsies from five regions of the intestine of 10 patients. The mRNA expression levels of CNT1, CNT2, apical sodium-dependent bile acid transporter (ABST), serotonin transporter (SERT), PEPT1, and OCTN2 exhibit marked differences between different regions of the intestine: the first five are predominantly expressed in the small intestine, whereas OCTN2 exhibits strongest expression in the colon. Two transporter mRNAs studied (OCTN1, OATP2B1) are expressed at similar levels in all gut sections. In addition, ENT2 mRNA is present at low levels across the colon, but not in the small intestine. The other six SLC mRNAs studied are not expressed in the intestine. Quantitative knowledge of transporter expression levels in different regions of the human gastrointestinal tract could be useful for designing intestinal delivery strategies for orally administered drugs. Furthermore, changes in transporter expression that occur in pathological states, such as inflammatory bowel disease, can now be defined more precisely by comparison with the expression levels measured in healthy individuals.
Footnotes
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This study was supported by Grants PP00B-108511/1 (to G.A.K.-U.), 32-114009/1 (to S.R.V.), and 3347CO-108792/1 (Swiss IBD Cohort Study) from the Swiss National Science Foundation; by a grant from the Kamillo Eisner Stiftung (Hergiswil, Switzerland; no. 49; to G.A.K.-U.); and grants from the University of Zurich (to S.R.V.) and the Novartis Foundation for Biomedical Research (to S.R.V.).
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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.106.013342.
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ABBREVIATIONS: SLC, solute carrier; CNT, concentrative nucleoside transporter; ASBT, apical sodium-dependent bile acid transporter; SERT, serotonin transporter; PEPT, peptide transporter; OCTN, organic zwitterion/cation transporter; OATP, organic anion transporting polypeptide; ENT, equilibrative nucleoside transporter; IBD, inflammatory bowel disease; 5-HT, 5-hydroxytryptamine; IBS, irritable bowel syndrome; OCT, organic cation transporter; MCT1, monocarboxylate transporter; OAT, organic anion transporter; 5-HT, 5-hydroxytryptamine; PCR, polymerase chain reaction.
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↵ The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
- Received October 16, 2006.
- Accepted January 11, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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