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Cited by 188Drug Transport and Resistance MechanismsAmino Acid Enzymes and MetabolismIon Transport and Channel Regulation

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

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Thwaites, David T., Anderson, Catriona M. H.·2007·Experimental Physiology
DOI 10.1113/expphysiol.2005.029959PMC PMC2803310
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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.

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  • Several Na-dependent nutrient co-transporters including SGLT1 depend on the pump activity of the Na-K-ATPase at the basolateral membrane to maintain low levels of intracellular Na and provide a favorable electrochemical gradient necessary for their functioning.

    “In addition, several Na-dependent nutrient co-transporters including SGLT1 depend on the pump activity of the Na-K-ATPase at the basolateral membrane to maintain low levels of intracellular Na in order to provide a favorable electrochemical gradient necessary for their functioning [53,54].”

    From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [53]

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  1. Abbot EL Grenade DS Kennedy DJ Gatfield KM Thwaites DT Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H+-coupled amino acid transporter hPAT1 Br J Pharmacol 2006 147 298 306 16331283 PMC1751303
  2. Anderson CMH Grenade DS Boll M Foltz M Wake KA Kennedy DJ Munck LK Miyauchi S Taylor PM Campbell FC Munck BG Daniel H Ganapathy V Thwaites DT H+/amino acid transporter 1 (PAT1) is the imino acid carrier: an intestinal nutrient/drug transporter in human and rat Gastroenterology 2004 127 1410 1422 15521011
  3. Anderson CMH Mendoza ME Kennedy DJ Raldua D Thwaites DT Inhibition of intestinal dipeptide transport by the neuropeptide VIP is an anti-absorptive effect via the VPAC1 receptor in a human enterocyte-like cell line (Caco-2) Br J Pharmacol 2003 138 564 573 12598410 PMC1573691
  4. Anderson CMH Thwaites DT Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1) J Cell Physiol 2005 204 604 613 15754324
  5. Anderson CMH Thwaites DT Regulation of intestinal hPepT1 (SLC15A1) activity by phosphodiesterase inhibitors is via inhibition of NHE3 (SLC9A3) Biochim Biophys Acta 2007 1768 1822 1829 17498647 PMC2428106
  6. Auger C Attwell D Fast removal of synaptic glutamate by postsynaptic transporters Neuron 2000 28 547 558 11144363
  7. Bannon DI Abounader R Lees PS Bressler JP Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells Am J Physiol 2003 284 C44 C50 12388109
  8. Bauerly KA Kelleher SL Lönnerdal B Functional and molecular responses of suckling rat pups and human intestinal Caco-2 cells to copper treatment J Nutr Biochem 2004 15 155 162 15023397
  9. Bermingham JR Pennington J Organization and expression of the SLC36 cluster of amino acid transporter genes Mamm Genome 2004 14 114 125 15058382
  10. Berteloot A Characteristics of glutamic acid transport by rabbit intestinal brush-border membrane vesicles. Effects of Na+-, K+- and H+-gradients Biochim Biophys Acta 1984 775 129 140 6147159
  11. Boll M Daniel H Gasnier B The SLC36 family: proton-coupled transporters for absorption of selected amino acids from extracellular and intracellular proteolysis Pflügers Archiv 2004 447 776 779 12748860
  12. Boll M Foltz M Anderson CMH Oechsler C Kottra G Thwaites DT Daniel H Substrate recognition by the mammalian proton-dependent amino acid transporter PAT1 Mol Membr Biol 2003 20 261 269 12893527
  13. Boll M Foltz M Rubio-Aliaga I Kottra G Daniel H Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters J Biol Chem 2002 277 22966 22973 11959859
  14. Boll M Markovich D Weber WM Korte H Daniel H Murer H Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, β-lactam antibiotics and ACE-inhibitors Pflügers Archiv 1994 429 146 149 7708476
  15. Boyd CAR Ward MR A micro-electrode study of oligopeptide absorption by the small intestinal epithelium of Necturus maculosus J Physiol 1982 324 411 428 7097606 PMC1250714
  16. Brant SR Yun CHC Donowitz M Tse CM Cloning, tissue distribution, and functional analysis of the human Na+/H+ exchanger isoform, NHE3 Am J Physiol 1995 269 C198 C206 7631746
  17. Bröer A Klingel K Kowalczuk S Rasko JE Cavanaugh J Bröer S Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder J Biol Chem 2004 279 24467 24476 15044460
  18. Bröer S Schneider HP Bröer A Rahman B Hamprecht B Deitmer JW Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH Biochem J 1998 333 167 174 9639576 PMC1219569
  19. Buyse M Sitaraman SV Liu X Bado A Merlin D Luminal leptin enhances CD147/MCT-1-mediated uptake of butyrate in the human intestinal cell line Caco2-BBE J Biol Chem 2002 277 28182 28190 12034734
  20. Canonne-Hergaux F Gruenheid S Ponka P Gros P Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron Blood 1999 93 4406 4417 10361139
  21. Chen NH Reith ME Quick MW Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6 Pflügers Archiv 2004 447 519 31 12719981
  22. Chen Z Fei YJ Anderson CMH Wake KA Miyauchi S Huang W Thwaites DT Ganapathy V Structure, function and immunolocalization of a proton-coupled amino acid transporter (hPAT1) in the human intestinal cell line Caco-2 J Physiol 2003a 546 349 361 12527723 PMC2342508
  23. Chen Z Kennedy DJ Wake KA Zhuang L Ganapathy V Thwaites DT Structure, tissue expression pattern, and function of the amino acid transporter rat PAT2 Biochem Biophys Res Commun 2003b 304 747 754 12727219
  24. Christensen HN Naming plan for membrane transport systems for amino acids Neurochem Res 1984 9 1757 1758 6531071
  25. Coady MJ Chang MH Charron FM Plata C Wallendorff B Sah JF Markowitz SD Romero MF Lapointe JY The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter J Physiol 2004 557 719 731 15090606 PMC1665153
  26. Crane RK Hypothesis for mechanism of intestinal active transport of sugars Fed Proc 1962 21 891 895 14023681
  27. Crane RK Miller D Bihler I Kleinzeller A Kotyk A The restrictions on possible mechanism of intestinal active transport of sugars Membrane Transport and Metabolism 1961 439 449 Academic Press London
  28. Csáky TZ Thale M Effect of ionic environment on intestinal sugar transport J Physiol 1960 151 59 65 13813138 PMC1363219
  29. Curran PF Na, Cl, and water transport by rat ileum in vitro J Gen Physiol 1960 43 1137 1148 13813357 PMC2195073
  30. Daniel H Fett C Kratz A Demonstration and modification of intervillous pH profiles in rat small intestine in vitro Am J Physiol 1989 257 G489 G495 2552822
  31. Daniel H Kottra G The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology Pflügers Archiv 2004 447 610 618 12905028
  32. Daniel H Neugebauer B Kratz A Rehner G Localization of acid microclimate along intestinal villi of rat jejunum Am J Physiol 1985 248 G293 G298 3976888
  33. Daniel H Rehner G Effect of metabolizable sugars on the mucosal surface pH of rat intestine J Nutr 1986 116 768 777 3701457
  34. Dantzig AH Bergin L Uptake of the cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2 Biochim Biophys Acta 1990 1027 211 217 2397233
  35. Delie F Rubas W A human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model Crit Rev Ther Drug Carrier Syst 1997 14 221 286 9282267
  36. Dixon KH Lanpher BC Chiu J Kelley K Cowan KH A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells J Biol Chem 1994 269 17 20 8276792
  37. Dresser GK Bailey DG Leake BF Schwarz UI Dawson PA Freeman DJ Kim RB Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine Clin Pharmacol Ther 2002 71 11 20 11823753
  38. Englund G Rorsman F Ronnblom A Karlbom U Lazorova L Grasjo J Kindmark A Artursson P Regional levels of drug transporters along the human intestinal tract: co-expression of ABC and SLC transporters and comparison with Caco-2 cells Eur J Pharm Sci 2006 29 269 277 16822659
  39. Fei YJ Kanai Y Nussberger S Ganapathy V Leibach FH Romero MF Singh SK Boron WF Hediger MA Expression cloning of a mammalian proton-coupled oligopeptide transporter Nature 1994 368 563 566 8139693
  40. Fleming MD Romano MA Su MA Garrick LM Garrick MD Andrews NC Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport Proc Natl Acad Sci USA 1998 95 1148 1153 9448300 PMC18702
  41. Foltz M Boll M Raschka L Kottra G Daniel H A novel bifunctionality: PAT1 and PAT2 mediate electrogenic proton/amino acid and electroneutral proton/fatty acid symport FASEB J 2004a 18 1758 1760 15345686
  42. Foltz M Oechsler C Boll M Kottra G Daniel H Substrate specificity and transport mode of the proton-dependent amino acid transporter mPAT2 Eur J Biochem 2004b 271 3340 3347 15291811
  43. Freeman TC Bentsen BS Thwaites DT Simmons NL H+/di-tripeptide transporter (PepT1) expression in the rabbit intestine Pflügers Archiv 1995 430 394 400 7491264
  44. Freeman TC Collins AJ Heavens RP Tivey DR Genetic regulation of enterocyte function: a quantitative in situ hybridisation study of lactase-phlorizin hydrolase and Na+-glucose cotransporter mRNAs in rabbit small intestine Pflügers Archiv 1993 422 570 576 8469609
  45. Ganapathy V Burckhardt G Leibach FH Characteristics of glycylsarcosine transport in rabbit intestinal brush-border membrane vesicles J Biol Chem 1984 259 8954 8959 6746633
  46. Ganapathy V Gopal E Miyauchi S Prasad PD Biological functions of SLC5A8, a candidate tumour suppressor Biochem Soc Trans 2005 33 237 240 15667316
  47. Ganapathy V Gupta N Martindale RG Johnson LR Protein digestion and absorption Physiology of the Gastrointestinal Tract 2006 1667 1692 Elsevier San Diego
  48. Ganapathy V Leibach FH Role of pH gradient and membrane potential in dipeptide transport in intestinal and renal brush-border membrane vesicles from the rabbit J Biol Chem 1983 258 14189 14192 6643475
  49. Ganapathy V Leibach FH Is intestinal peptide transport energized by a proton gradient? Am J Physiol 1985 249 G153 G160 2992286
  50. Ganapathy V Smith SB Prasad PD SLC19: the folate/thiamine transporter family Pflügers Archiv 2004 447 641 646 14770311
  51. Garcia CK Brown MS Pathak RK Goldstein JL cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1 J Biol Chem 1995 270 1843 1849 7829520
  52. Garcia CK Goldstein JL Pathak RK Anderson RG Brown MS Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle Cell 1994 76 865 873 8124722
  53. Gill RK Saksena S Alrefai WA Sarwar Z Goldstein JL Carroll RE Ramaswamy K Dudeja PK Expression and membrane localization of MCT isoforms along the length of the human intestine Am J Physiol 2005 289 C846 C852 15901598
  54. Goberdhan DCI Meredith D Boyd CAR Wilson C PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids Development 2005 132 2365 2375 15843412
  55. Gopal E Fei YJ Sugawara M Miyauchi S Zhuang L Martin P Smith SB Prasad PD Ganapathy V Expression of slc5a8 in kidney and its role in Na+-coupled transport of lactate J Biol Chem 2004 279 44522 44532 15322102
  56. Gray JH Owen RP Giacomini KM The concentrative nucleoside transporter family, SLC28 Pflügers Archiv 2004 447 728 734 12856181
  57. Grube M Kock K Oswald S Draber K Meissner K Eckel L Bohm M Felix SB Vogelgesang S Jedlitschky G Siegmund W Warzok R Kroemer HK Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart Clin Pharmacol Ther 2006 80 607 620 17178262
  58. Hadjiagapiou C Schmidt L Dudeja PK Layden TJ Ramaswamy K Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1 Am J Physiol 2000 279 G775 G780 11005765
  59. Hagenbuch B Dawson P The sodium bile salt cotransport family SLC10 Pflügers Archiv 2004 447 566 70 12851823
  60. Hagenbuch B Meier PJ The superfamily of organic anion transporting polypeptides Biochim Biophys Acta 2003 1609 1 18 12507753
  61. Hagenbuch B Meier PJ Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties Pflügers Archiv 2004 447 653 665 14579113
  62. Halestrap AP Meredith D The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond Pflügers Archiv 2004 447 619 628 12739169
  63. Harig JM Rajendran VM Barry JA Ramaswamy K Transport characteristics of L-glutamate in human jejunal brush-border membrane vesicles Biochim Biophys Acta 1987 903 358 364 2888487
  64. Hatanaka T Haramura M Fei YJ Miyauchi S Bridges CC Ganapathy PS Smith SB Ganapathy V Ganapathy ME Transport of amino acid-based prodrugs by the Na+- and Cl+-coupled amino acid transporter ATB0,+ and expression of the transporter in tissues amenable for drug delivery J Pharmacol Exp Ther 2004 308 1138 1147 14617696
  65. Hediger MA Structure, function and evolution of solute transporters in prokaryotes and eukaryotes J Exp Biol 1994 196 15 49 7823018
  66. Hediger MA Coady MJ Ikeda TS Wright EM Expression cloning and cDNA sequencing of the Na+/glucose co-transporter Nature 1987 330 379 381 2446136
  67. Henderson PJF Proton-linked sugar transport systems in bacteria J Bioenerg Biomembr 1990 22 525 569 2172229
  68. Hirayama BA Loo DD Wright EM Protons drive sugar transport through the Na+/glucose cotransporter (SGLT1) J Biol Chem 1994 269 21407 21410 8063771
  69. Hogben CAM Tocco DJ Brodie BB Schanker LS On the mechanism of intestinal absorption of drugs J Pharmacol Exp Ther 1959 125 275 282 13642268
  70. Hoogerwerf WA Tsao SC Devuyst O Levine SA Yun CH Yip JW Cohen ME Wilson PD Lazenby AJ Tse CM Donowitz M NHE2 and NHE3 are human and rabbit intestinal brush-border proteins Am J Physiol 1996 270 G29 G41 8772498
  71. Hopfer U Nelson K Perrotto J Isselbacher KJ Glucose transport in isolated brush border membrane from rat small intestine J Biol Chem 1973 248 25 32 4692832
  72. Hoshi T Takuwa N Abe M Tajima A Hydrogen ion-coupled transport of D-glucose by phlorizin-sensitive sugar carrier in intestinal brush-border membranes Biochim Biophys Acta 1986 861 483 488 3768358
  73. Hwang ES Hirayama BA Wright EM Distribution of the SGLT1 Na+/glucose cotransporter and mRNA along the crypt-villus axis of rabbit small intestine Biochem Biophys Res Commun 1991 181 1208 1217 1764071
  74. Iñigo C Barber A Lostao MP Na+ and pH dependence of proline and β-alanine absorption in rat small intestine Acta Physiol 2006 186 271 278 16634782
  75. Inui K Yamamoto M Saito H Transepithelial transport of oral cephalosporins by monolayers of intestinal epithelial cell line Caco-2: specific transport systems in apical and basolateral membranes J Pharmacol Exp Ther 1992 261 195 201 1560365
  76. Iwanaga T Goto M Watanabe M Cellular distribution of glutamate transporters in the gastrointestinal tract of mice: an immunohistochemical and in situ hybridization approach Biomed Res 2005 26 271 278 16415508
  77. Iwanaga T Takebe K Kato I Karaki S Kuwahara A Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8 Biomed Res 2006 27 243 254 17099289
  78. Kanai Y Hediger MA Primary structure and functional characterization of a high-affinity glutamate transporter Nature 1992 360 467 471 1280334
  79. Kanai Y Stelzner M Nussberger S Khawaja S Hebert SC Smith CP Hediger MA The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport J Biol Chem 1994 269 20599 20606 7914198
  80. Kennedy DJ Gatfield KM Winpenny JP Ganapathy V Thwaites DT Substrate specificity and functional characterisation of the H+/amino acid transporter rat PAT2 (Slc36a2) Br J Pharmacol 2005a 144 28 41 15644866 PMC1575977
  81. Kennedy DJ Leibach FH Ganapathy V Thwaites DT Optimal absorptive transport of the dipeptide glycylsarcosine is dependent on functional Na+/H+ exchange activity Pflügers Archiv 2002 445 139 146 12397398
  82. Kennedy DJ Raldua D Thwaites DT Dual modes of 5-(N-ethyl-N-isopropyl)amiloride modulation of apical dipeptide uptake in the human small intestinal epithelial cell line Caco-2 Cell Mol Life Sci 2005b 62 1621 1631 15968466 PMC11139100
  83. Khoursandi S Scharlau D Herter P Kuhnen C Martin D Kinne RK Kipp H Different modes of sodium-D-glucose cotransporter-mediated D-glucose uptake regulation in Caco-2 cells Am J Physiol 2004 287 C1041 C1047 15201142
  84. Kim CM Goldstein JL Brown MS cDNA cloning of MEV, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function J Biol Chem 1992 267 23113 23121 1429658
  85. Klomp AE Tops BB Van Denberg IE Berger R Klomp LW Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1) Biochem J 2002 364 497 505 12023893 PMC1222595
  86. Kneuer C Honscha W The H+-dependent reduced folate carrier 1 of humans and the sodium-dependent methotrexate carrier-1 of the rat are orthologs FEBS Lett 2004 566 83 86 15147873
  87. Kobayashi D Nozawa T Imai K Nezu J Tsuji A Tamai I Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane J Pharmacol Exp Ther 2003 306 703 708 12724351
  88. Kowalczuk S Bröer A Munzinger M Tietze N Klingel K Bröer S Molecular cloning of the mouse IMINO system: an Na+- and Cl−-dependent proline transporter Biochem J 2005 386 417 22 15689184 PMC1134859
  89. Kullak-Ublick GA Ismair MG Stieger B Landmann L Huber R Pizzagalli F Fattinger K Meier PJ Hagenbuch B Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver Gastroenterology 2001 120 525 533 11159893
  90. Kumar CK Nguyen TT Gonzales FB Said HM Comparison of intestinal folate carrier clone in IEC-6 cells and in Xenopus oocytes Am J Physiol 1998 274 C289 C294 9458739
  91. Kuo YM Gybina AA Pyatskowit JW Gitschier J Prohaska JR Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status J Nutr 2006 136 21 26 16365053 PMC2718570
  92. Lee J Pena MM Nose Y Thiele DJ Biochemical characterization of the human copper transporter Ctr1 J Biol Chem 2002 277 4380 4387 11734551
  93. Liang R Fei YJ Prasad PD Ramamoorthy S Han H Yang-Feng TL Hediger MA Ganapathy V Leibach FH Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization J Biol Chem 1995 270 6456 6463 7896779
  94. Lucas ML Lei FH Blair JA The influence of buffer pH, glucose and sodium ion concentration on the acid microclimate in rat proximal jejunum in vitro Pflügers Archiv 1980 385 137 142 7190271
  95. Lucas ML Schneider W Haberich FJ Blair JA Direct measurement by pH-microelectrode of the pH microclimate in rat proximal jejunum Proc R Soc Lond B 1975 192 39 48 1788
  96. Mackenzie B Hediger MA SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1 Pflügers Archiv 2004 447 571 579 14530973
  97. Mackenzie B Garrick MD Iron Imports. II. Iron uptake at the apical membrane in the intestine Am J Physiol 2005 289 G981 G986 16286504
  98. Maenz DD Chenu C Breton S Berteloot A pH-dependent heterogeneity of acidic amino acid transport in rabbit jejunal brush border membrane vesicles J Biol Chem 1992 267 1510 1516 1346136
  99. Markovich D Murer H The SLC13 gene family of sodium sulphate/carboxylate cotransporters Pflügers Archiv 2004 447 594 602 12915942
  100. Martel F Monteiro R Lemos C Uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells occurs through the neuronal serotonin transporter (SERT) J Pharmacol Exp Ther 2003 306 355 62 12682218
  101. Martin-Venegas R Rodriguez-Lagunas MJ Geraert PA Ferrer R Monocarboxylate transporter 1 mediates dl-2-Hydroxy-(4-methylthio)butanoic acid transport across the apical membrane of Caco-2 cell monolayers J Nutr 2007 137 49 54 17182800
  102. Mason JB Shoda R Haskell M Selhub J Rosenberg IH Carrier affinity as a mechanism for the pH-dependence of folate transport in the small intestine Biochim Biophys Acta 1990 1024 331 335 2354183
  103. McEwan GTA Daniel H Fett C Burgess MN Lucas ML The effect of Escherichia coli STa enterotoxin and other secretagogues on mucosal surface pH of rat small intestine in vivo Proc R Soc Lond B 1988 234 219 237 2905462
  104. McKie AT Kusel M McEwan GTA Lucas ML The effect of heat stable Escherichia coli enterotoxin, theophylline and forskolin on cyclic nucleotide levels and mucosal surface (acid microclimate) pH in rat proximal jejunum in vivo Biochim Biophys Acta 1988 971 325 331 2844294
  105. Metzner L Kalbitz J Brandsch M Transport of pharmacologically active proline derivatives by the human proton-coupled amino acid transporter hPAT1 J Pharmacol Exp Ther 2004 309 28 35 14718599
  106. Metzner L Kottra G Neubert K Daniel H Brandsch M Serotonin, l-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1 FASEB J 2005 19 1468 1473 16126914
  107. Mitchell P Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism Nature 1961 191 144 8 13771349
  108. Mitchell P Performance and conservation of osmotic work by proton-coupled solute porter systems Bioenergetics 1973 4 63 91 4268692
  109. Miyauchi S Abbot EL Zhuang L Subramanian R Ganapathy V Thwaites DT Isolation and function of the amino acid transporter PAT1 (slc36a1) from rabbit and discrimination between transport via PAT1 and system IMINO in renal brush-border membrane vesicles Mol Membr Biol 2005 22 549 559 16373326
  110. Murer H Forster I Biber J The sodium phosphate cotransporter family SLC34 Pflügers Archiv 2004 447 763 767 12750889
  111. Murer H Hopfer U Kinne R Sodium/proton antiport in brush-border membrane vesicles isolated from rat small intestine and kidney Biochem J 1976 154 597 604 942389 PMC1172760
  112. Nguyen TT Dyer DL Dunning DD Rubin SA Grant KE Said HM Human intestinal folate transport: cloning, expression, and distribution of complementary RNA Gastroenterology 1997 112 783 791 9041240
  113. Nose Y Kim BE Thiele DJ Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function Cell Metab 2006 4 235 244 16950140
  114. Nozawa T Imai K Nezu J Tsuji A Tamai I Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human J Pharmacol Exp Ther 2004 308 438 445 14610227
  115. Nozawa T Nakajima M Tamai I Noda K Nezu JI Sai Y Tsuji A Yokoi T Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis J Pharmacol Exp Ther 2002 302 804 813 12130747
  116. Orlowski J Heterologous expression and functional properties of amiloride high affinity (NHE-1) and low affinity (NHE-3) isoforms of the rat Na/H exchanger J Biol Chem 1993 268 16369 16377 8393860
  117. Petris MJ The SLC31 (Ctr) copper transporter family Pflügers Archiv 2004 447 752 755 12827356
  118. Prasad PD Ramamoorthy S Leibach FH Ganapathy V Molecular cloning of the human placental folate transporter Biochem Biophys Res Commun 1995 206 681 687 7826387
  119. Qiu A Jansen M Sakaris A Min SH Chattopadhyay S Tsai E Sandoval C Zhao R Akabas MH Goldman ID Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption Cell 2006 127 917 928 17129779
  120. Quick M Loo DD Wright EM Neutralization of a conserved amino acid residue in the human Na+/glucose transporter (hSGLT1) generates a glucose-gated H+ channel J Biol Chem 2001 276 1728 1734 11024018
  121. Ricklis E Quastel JH Effects of cations on sugar absorption by isolated surviving guinea pig intestine Can J Biochem Physiol 1958 36 347 362 13511241
  122. Riggs TR Walker LM Christensen HN Potassium migration and amino acid transport J Biol Chem 1958 233 1479 1484 13610858
  123. Ritzhaupt A Wood IS Ellis A Hosie KB Shirazi-Beechey SP Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate J Physiol 1998 513 719 732 9824713 PMC2231331
  124. Rome S Barbot L Windsor E Kapel N Tricottet V Huneau JF Reynes M Gobert JG Tome D The regionalization of PepT1, NBAT and EAAC1 transporters in the small intestine of rats are unchanged from birth to adulthood J Nutr 2002 132 1009 1011 11983829
  125. Rubio-Aliaga I Boll M Vogt-Weisenhorn DM Foltz M Kottra G Daniel H The proton/amino acid cotransporter PAT2 is expressed in neurons with a different subcellular localization than its paralog PAT1 J Biol Chem 2004 279 2754 2760 14600155
  126. Rubio-Aliaga I Daniel H Mammalian peptide transporters as targets for drug delivery Trends Pharmacol Sci 2002 23 434 440 12237156
  127. Sagné C Agulhon C Ravassard P Darmon M Hamon M El Mestikawy S Gasnier B Giros B Identification and characterization of a lysosomal transporter for small neutral amino acids Proc Natl Acad Sci USA 2001 98 7206 7211 11390972 PMC34647
  128. Sai Y Kaneko Y Ito S Mitsuoka K Kato Y Tamai I Artursson P Tsuji A Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells Drug Metab Dispos 2006 34 1423 1431 16714376
  129. Said HM Chatterjee N Haq RU Subramanian VS Ortiz A Matherly LH Sirotnak FM Halsted C Rubin SA Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency Am J Physiol 2000 279 C1889 C1895 11078704
  130. Said HM Ghishan FK Redha R Folate transport by human intestinal brush-border membrane vesicles Am J Physiol 1987 252 G229 G236 3826350
  131. Said HM Nguyen TT Dyer DL Cowan KH Rubin SA Intestinal folate transport: identification of a cDNA involved in folate transport and the functional expression and distribution of its mRNA Biochim Biophys Acta 1996 1281 164 172 8664315
  132. Satoh H Yamashita F Tsujimoto M Murakami H Koyabu N Ohtani H Sawada Y Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B Drug Metab Dispos 2005 33 518 523 15640378
  133. Schanker LS Tocco DJ Brodie BB Hogben CAM Absorption of drugs from the rat small intestine J Pharmacol Exp Ther 1958 123 81 88 13539795
  134. Schron CM Washington C Blitzer BL The transmembrane pH gradient drives uphill folate transport in rabbit jejunum. Direct evidence for folate/hydroxyl exchange in brush border membrane vesicles J Clin Invest 1985 76 2030 2033 4056063 PMC424271
  135. Schultz SG Zalusky R Ion transport in isolated rabbit ileum. II. The interaction between active sodium and active sugar transport J Gen Physiol 1964 47 1043 1059 14192544 PMC2195378
  136. Seithel A Karlsson J Hilgendorf C Bjorquist A Ungell AL Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: comparison between human segments and Caco-2 cells Eur J Pharm Sci 2006 28 291 299 16704924
  137. Selhub J Rosenberg IH Folate transport in isolated brush border membrane vesicles from rat intestine J Biol Chem 1981 256 4489 4493 7217093
  138. Shiau YF Fernandez P Jackson MJ McMonagle S Mechanisms maintaining a low-pH microclimate in the intestine Am J Physiol 1985 248 G608 G617 3890561
  139. Shimada T Factors effecting the microclimate pH in rat jejunum J Physiol 1987 392 113 127 3446778 PMC1192296
  140. Shimada T Hoshi T Na+-dependent elevation of the acidic cell surface pH (microclimate pH) of rat jejunal villus cells induced by cyclic nucleotides and phorbol ester: possible mediators of the regulation of the Na+/H+ antiporter Biochim Biophys Acta 1988 937 328 334 2827772
  141. Simanjuntak MT Tamai I Terasaki T Tsuji A Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport J Pharmacobiodyn 1990 13 301 309 2273446
  142. Skulachev VP Chemiosmotic concept of the membrane bioenergetics: what is already clear and what is still waiting for elucidation? J Bioenerg Biomembr 1994 26 589 598 7721720
  143. Smith MW Turvey A Freeman TC Appearance of phloridzin-sensitive glucose transport is not controlled at mRNA level in rabbit jejunal enterocytes Exp Physiol 1992 77 525 528 1632962
  144. Srinivas SR Gopal E Zhuang L Itagaki S Martin PM Fei YJ Ganapathy V Prasad PD Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2) Biochem J 2005 392 655 664 16104846 PMC1316307
  145. Stein J Zores M Schroder O Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism Eur J Nutr 2000 39 121 125 10918994
  146. Su MA Trenor CC Fleming JC Fleming MD Andrews NC The G185R mutation disrupts function of the iron transporter Nramp2 Blood 1998 92 2157 63 9731075
  147. Takanaga H Mackenzie B Hediger MA Sodium-dependent ascorbic acid transporter family SLC23 Pflügers Archiv 2004 447 677 682 12845532
  148. Takanaga H Mackenzie B Suzuki Y Hediger MA Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino J Biol Chem 2005 280 8974 8984 15632147
  149. Takanaga H Maeda H Yabuuchi H Tamai I Higashida H Tsuji A Nicotinic acid transport mediated by pH-dependent anion antiporter and proton cotransporter in rabbit intestinal brush-border membrane J Pharm Pharmacol 1996 48 1073 1077 8953511
  150. Takanaga H Tamai I Inaba S Sai Y Higashida H Yamamoto H Tsuji A cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter Biochem Biophys Res Commun 1995 217 370 377 8526936
  151. Tamai I Nezu J Uchino H Sai Y Oku A Shimane M Tsuji A Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family Biochem Biophys Res Commun 2000 273 251 260 10873595
  152. Tamai I Sai Y Ono A Kido Y Yabuuchi H Takanaga H Satoh E Ogihara T Amano O Izeki S Tsuji A Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1 J Pharm Pharmacol 1999 51 1113 1121 10579682
  153. Tamai I Takanaga H Maeda H Ogihara T Yoneda M Tsuji A Proton-cotransport of pravastatin across intestinal brush-border membrane Pharm Res 1995a 12 1727 1732 8592677
  154. Tamai I Takanaga H Maeda H Sai Y Ogihara T Higashida H Tsuji A Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids Biochem Biophys Res Commun 1995b 214 482 489 7677755
  155. Tandy S Williams M Leggett A Lopez-Jimenez M Dedes M Ramesh B Srai SK Sharp P Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells J Biol Chem 2000 275 1023 1029 10625641
  156. Thwaites DT Anderson CMH Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1 Biochim Biophys Acta 2007 1768 179 197 17123464
  157. Thwaites DT Armstrong G Hirst BH Simmons NL d-Cycloserine transport in human intestinal epithelial (Caco-2) cells: mediation by a H+-coupled amino acid transporter Br J Pharmacol 1995a 115 761 766 8548174 PMC1908525
  158. Thwaites DT Basterfield L McCleave PMJ Carter SM Simmons NL Gamma-aminobutyric acid (GABA) transport across human intestinal epithelial (Caco-2) cell monolayers Br J Pharmacol 2000 129 457 464 10711343 PMC1571855
  159. Thwaites DT Brown CDA Hirst BH Simmons NL Transepithelial glycylsarcosine transport in intestinal Caco-2 cells mediated by expression of H+-coupled carriers at both apical and basal membranes J Biol Chem 1993a 268 7640 7642 8463293
  160. Thwaites DT Brown CDA Hirst BH Simmons NL H+-coupled dipeptide (glycylsarcosine) transport across apical and basal borders of human intestinal Caco-2 cell monolayers display distinctive characteristics Biochim Biophys Acta 1993b 1151 237 245 8373798
  161. Thwaites DT Ford D Glanville M Simmons NL H+/solute-induced intracellular acidification leads to selective activation of apical Na+/H+ exchange in human intestinal epithelial cells J Clin Invest 1999 104 629 635 10487777 PMC408543
  162. Thwaites DT Hirst BH Simmons NL Direct assessment of dipeptide/H+ symport in intact human intestinal (Caco-2) epithelium: a novel method utilising continuous intracellular pH measurement Biochem Biophys Res Commun 1993c 194 432 438 8333858
  163. Thwaites DT Hirst BH Simmons NL Substrate specificity of the di/tripeptide transporter in human intestinal epithelia (Caco-2): identification of substrates that undergo H+-coupled absorption Br J Pharmacol 1994a 113 1050 1056 7858848 PMC1510430
  164. Thwaites DT Kennedy DJ Raldua D Anderson CMH Mendoza ME Bladen CL Simmons NL H+/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na+/H+ exchanger Gastroenterology 2002 122 1322 1333 11984519
  165. Thwaites DT McEwan GTA Brown CDA Hirst BH Simmons NL Na+-independent, H+-coupled transepithelial β-alanine absorption by human intestinal Caco-2 cell monolayers J Biol Chem 1993d 268 18438 18441 8395502
  166. Thwaites DT McEwan GTA Brown CDA Hirst BH Simmons NL l-Alanine absorption in human intestinal Caco-2 cells driven by the proton electrochemical gradient J Membr Biol 1994b 140 143 151 7932648
  167. Thwaites DT McEwan GTA Cook MJ Hirst BH Simmons NL H+-coupled (Na+-independent) proline transport in human intestinal (Caco-2) epithelial cell monolayers FEBS Lett 1993e 333 78 82 8224175
  168. Thwaites DT McEwan GTA Hirst BH Simmons NL Transepithelial dipeptide (glycylsarcosine) transport across epithelial monolayers of human Caco-2 cells is rheogenic Pflügers Archiv 1993f 425 178 180 8272376
  169. Thwaites DT McEwan GTA Hirst BH Simmons NL H+-coupled α-methylaminoisobutyric acid transport in human intestinal Caco-2 cells Biochim Biophys Acta 1995b 1234 111 118 7880851
  170. Thwaites DT McEwan GTA Simmons NL The role of the proton electrochemical gradient in the transepithelial absorption of amino acids by human intestinal Caco-2 cell monolayers J Membr Biol 1995c 145 245 256 7563025
  171. Thwaites DT Stevens BC H+/zwitterionic amino acid symport at the brush-border membrane of human intestinal epithelial (Caco-2) cells Exp Physiol 1999 84 275 284 10226170
  172. Tiruppathi C Balkovetz DF Ganapathy V Miyamoto Y Leibach FH A proton gradient, not a sodium gradient, is the driving force for active transport of lactate in rabbit intestinal brush-border membrane vesicles Biochem J 1988 256 219 223 2851979 PMC1135390
  173. Tsuchiya T Wilson TH Cation-sugar cotransport in the melibiose transport system of Escherichia coli Membr Biochem 1978 2 63 79 45782
  174. Vidal S Belouchi AM Cellier M Beatty B Gros P Cloning and characterization of a second human NRAMP gene on chromosome 12q13 Mamm Genome 1995 6 224 230 7613023
  175. Vincent ML Russell RM Sasak V Folic acid uptake characteristics of a human colon carcinoma cell line, Caco-2. A newly-described cellular model for small intestinal epithelium Hum Nutr Clin Nutr 1985 39 355 360 4055425
  176. Walker D Thwaites DT Simmons NL Gilbert HJ Hirst BH Substrate upregulation of the human small intestinal peptide transporter, hPepT1 J Physiol 1998 507 697 706 9508831 PMC2230834
  177. Wang Y Rajgopal A Goldman ID Zhao R Preservation of folate transport activity with a low-pH optimum in rat IEC-6 intestinal epithelial cell lines that lack reduced folate carrier function Am J Physiol 2005 288 C65 C71 15385270
  178. Wang Y Zhao R Goldman ID Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for permetrexed distinct from the reduced folate carrier Clin Cancer Res 2004 10 6256 6264 15448015
  179. Wang Y Zhao R Russell RG Goldman ID Localization of the murine reduced folate carrier as assessed by immunohistochemical analysis Biochim Biophys Acta 2001 1513 49 54 11427193
  180. West I Mitchell P Proton-coupled β-galactoside translocation in non-metabolizing Escherichia coli Bioenergetics 1972 3 445 462 4570991
  181. West IC Lactose transport coupled to proton movements in Escherichia coli Biochem Biophys Res Commun 1970 41 655 661 4920870
  182. West IC Mitchell P Stoicheiometry of lactose-protein symport across the plasma membrane of Escherichia coli Biochem J 1973 132 587 592 4579628 PMC1177623
  183. Wipf D Ludewig U Tegeder M Rentsch D Koch W Frommer WB Conservation of amino acid transporters in fungi, plants and animals Trends Biochem Sci 2002 27 139 147 11893511
  184. Wright EM Loo DD Hirayama BA Turk E Surprising versatility of Na+-glucose cotransporters: SLC5 Physiology 2004 19 370 376 15546855
  185. Wright EM Turk E The sodium/glucose cotransport family SLC5 Pflügers Archiv 2004 447 510 518 12748858
  186. Wright EM Turk E Zabel B Mundlos S Dyer J Molecular genetics of intestinal glucose transport J Clin Invest 1991 88 1435 1440 1939637 PMC295642
  187. Wu X Whitfield LR Stewart BH Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter Pharm Res 2000 17 209 215 10751037
  188. Yoshida A Takata K Kasahara T Aoyagi T Saito S Hirano H Immunohistochemical localization of Na+-dependent glucose transporter in the rat digestive tract Histochem J 1995 27 420 426 7657561
  189. Zerangue N Kavanaugh MP Flux coupling in a neuronal glutamate transporter Nature 1996a 383 634 637 8857541
  190. Zerangue N Kavanaugh MP Interaction of l-cysteine with a human excitatory amino acid transporter J Physiol 1996b 493 419 423 8782106 PMC1158927
  191. Zhao R Gao F Goldman ID Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells Am J Physiol 2002 282 C1512 C1517 11997266
  192. Zhao R Goldman ID The molecular identity and characterization of a proton-coupled folate transporter PCFT; biological ramifications and impact on the activity of permetrexed Cancer Metastasis Rev 2007 26 129 139 17340171

Authors
Thwaites, D. T., & Anderson, C. M. H.
Affiliations
Newcastle University (GB)
ORCID
Venue
Experimental Physiology
Publisher
Wiley
Published
2007-07
Volume
92
Issue
4
Pages
603-619
ISSN
  • 0958-0670 (ISSN-L)
  • 1469-445X
DOI
10.1113/expphysiol.2005.029959
PMC
PMC2803310
OpenAlex
W1576609740
Cited by
188
References
205
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 12 · 2020: 6 · 2019: 11 · 2018: 15 · 2017: 8 · 2016: 14 · 2015: 7 · 2014: 12 · 2013: 20 · 2012: 8
FWCI
1.41
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2 d)
Locations
  • Experimental Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Wellcome Trust (078640, 078640/Z/05/Z)
  • Biotechnology and Biological Sciences Research Council (D17277)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
brush border membrane, small intestine, nutrient absorption, micronutrient transport, drug absorption, PepT1, PAT1, DMT1, OATP2B1, MCT1, proton-coupled folate transporter, SGLT1, EAAC1, NHE3, oral bioavailability, short-chain fatty acids, amino acid transport
MeSH terms
Peptide Transporter 1, Sodium-Hydrogen Exchanger 3, Monocarboxylate Transport Protein 1, Solute Carrier Family 11, Member 2, Animals, Humans, Intestinal Absorption, Intestine, Small, Sodium-Hydrogen Exchangers, Membrane Transport Proteins, Amino Acid Transport Systems, Amino Acid Transport Systems, Neutral, Organic Anion Transporters, Monocarboxylic Acid Transporters, Cation Transport Proteins, Symporters, Excitatory Amino Acid Transporter 3, Sodium-Glucose Transporter 1, Proton-Coupled Folate Transporter

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