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H + ‐coupled nutrient, micronutrient and drug transporters in the mammalian small intestine
Author(s) -
Thwaites David T.,
Anderson Catriona M. H.
Publication year - 2007
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.029959
Subject(s) - cotransporter , biochemistry , brush border , symporter , electrochemical gradient , transporter , antiporter , chemistry , dmt1 , bumetanide , organic anion transporter 1 , biology , ion transporter , membrane , sodium , vesicle , organic chemistry , gene
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.