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This Article Full Text Full Text (PDF) All Versions of this Article: 92/4/603    most recent expphysiol.2005.029959v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thwaites, D. T. Articles by Anderson, C. M. H. Search for Related Content PubMed PubMed Citation Articles by Thwaites, D. T. Articles by Anderson, C. M. H. Related Collections Review Articles

¹ Epithelial Research Group, Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK

The H⁺-electrochemical gradient was originally considered as a driving force for solute transport only across cellular membranes of bacteria, plants and yeast. However, in the mammalian small intestine, a H⁺-electrochemical gradient is present at the epithelial brush-border membrane in the form of an acid microclimate. Over recent years, a large number of H⁺-coupled cotransport mechanisms have been identified at the luminal membrane of the mammalian small intestine. These transporters are responsible for the initial stage in absorption of a remarkable variety of essential and non-essential nutrients and micronutrients, including protein digestion products (di/tripeptides and amino acids), vitamins, short-chain fatty acids and divalent metal ions. Proton-coupled cotransporters expressed at the mammalian small intestinal brush-border membrane include: the di/tripeptide transporter PepT1 (SLC15A1); the proton-coupled amino-acid transporter PAT1 (SLC36A1); the divalent metal transporter DMT1 (SLC11A2); the organic anion transporting polypeptide OATP2B1 (SLC02B1); the monocarboxylate transporter MCT1 (SLC16A1); the proton-coupled folate transporter PCFT (SLC46A1); the sodium–glucose linked cotransporter SGLT1 (SLC5A1); and the excitatory amino acid carrier EAAC1 (SLC1A1). Emerging research demonstrates that the optimal intestinal absorptive capacity of certain H⁺-coupled cotransporters (PepT1 and PAT1) is dependent upon function of the brush-border Na⁺–H⁺ exchanger NHE3 (SLC9A3). The high oral bioavailability of a large number of pharmaceutical compounds results, in part, from absorptive transport via the same H⁺-coupled cotransporters. Drugs undergoing H⁺-coupled cotransport across the intestinal brush-border membrane include those used to treat bacterial infections, hypercholesterolaemia, hypertension, hyperglycaemia, viral infections, allergies, epilepsy, schizophrenia, rheumatoid arthritis and cancer.

(Received 15 March 2007; accepted after revision 26 April 2007; first published online 13 July 2007)
Corresponding author D. T. Thwaites: Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK. Email: d.t.thwaites{at}ncl.ac.uk

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