H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine.
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.
Thwaites
David T
DT
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. d.t.thwaites@ncl.ac.uk
Anderson
Catriona M H
CM
D026905:Amino Acid Transport Systems / Q000502:physiology; D026921:Amino Acid Transport Systems, Neutral / Q000502:physiology; D000818:Animals; D027682:Cation Transport Proteins / Q000502:physiology; D050580:Excitatory Amino Acid Transporter 3 / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007421:Intestine, Small / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D027501:Monocarboxylic Acid Transporters / Q000502:physiology; D027361:Organic Anion Transporters / Q000502:physiology; D000074011:Peptide Transporter 1; D058979:Proton-Coupled Folate Transporter; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D027981:Symporters / Q000502:physiology; D000099233:Monocarboxylate Transport Protein 1; D000099236:Solute Carrier Family 11, Member 2
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D027682:Cation Transport Proteins; D050580:Excitatory Amino Acid Transporter 3; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D027361:Organic Anion Transporters; D000074011:Peptide Transporter 1; D058979:Proton-Coupled Folate Transporter; D051269:Sodium-Glucose Transporter 1; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; D000099236:Solute Carrier Family 11, Member 2; C082186:SLC15A1 protein, human; C475905:SLC36A1 protein, human; C505058:SLC46A1 protein, human; C000613385:SLC9A3 protein, human; C493537:Slc36a1 protein, rat; C000613387:Slc9a3 protein, rat