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H⁺-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine

Lookup NU author(s): Professor David Thwaites, Dr Catriona AndersonORCiD

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Abstract

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. © 2007 The Authors.

Publication metadata

Author(s): Thwaites DT, Anderson CMH

Publication type: Article

Publication status: Published

Journal: Experimental Physiology

Year: 2007

Volume: 92

Issue: 4

Pages: 603-619

Print publication date: 01/07/2007

ISSN (print): 0958-0670

ISSN (electronic): 1469-445X

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1113/expphysiol.2005.029959

DOI: 10.1113/expphysiol.2005.029959

PubMed id: 17468205

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