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

Experimental Physiology

Volumn 92, Issue 4, 2007, Pages 603-619

  Thwaites, David T ^a   Anderson, Catriona M H ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID TRANSPORTER; EXCITATORY AMINO ACID TRANSPORTER 3; HYDROGEN; SODIUM GLUCOSE COTRANSPORTER 1; SODIUM POTASSIUM CHLORIDE COTRANSPORTER; SODIUM PROTON EXCHANGE PROTEIN 3;

BRUSH BORDER; CELL MEMBRANE PERMEABILITY; DRUG TRANSPORT; ELECTROCHEMISTRY; HUMAN; INTESTINE EPITHELIUM CELL; NUTRIENT CONCENTRATION; PROTEIN TRANSPORT; PROTON SODIUM EXCHANGE; REVIEW; SMALL INTESTINE ABSORPTION;

EID: 34347379290     PISSN: 09580670     EISSN: 1469445X     Source Type: Journal    
DOI: 10.1113/expphysiol.2005.029959     Document Type: Review

References (201)

1. Abbot EL, Grenade DS, Kennedy DJ, Gatfield KM & Thwaites DT (2006). Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H+-coupled amino acid transporter hPAT1. Br J Pharmacol 147, 298 306.
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 (2004). H+/amino acid transporter 1 (PAT1) is the imino acid carrier: an intestinal nutrient/drug transporter in human and rat. Gastroenterology 127, 1410 1422.
3. Anderson CMH, Mendoza ME, Kennedy DJ, Raldua D & Thwaites DT (2003). 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 138, 564 573.
4. Anderson CMH & Thwaites DT (2005). Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1). J Cell Physiol 204, 604 613.
5. Anderson CMH & Thwaites DT (2007). Regulation of intestinal hPepT1 (SLC15A1) activity by phosphodiesterase inhibitors is via inhibition of NHE3 (SLC9A3). Biochim Biophys Acta doi :.
6. Auger C & Attwell D (2000). Fast removal of synaptic glutamate by postsynaptic transporters. Neuron 28, 547 558.
7. Bannon DI, Abounader R, Lees PS & Bressler JP (2003). Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am J Physiol Cell Physiol 284, C44 C50.
8. Bauerly KA, Kelleher SL & Lönnerdal B (2004). Functional and molecular responses of suckling rat pups and human intestinal Caco-2 cells to copper treatment. J Nutr Biochem 15, 155 162.
9. Bermingham JR & Pennington J (2004). Organization and expression of the SLC36 cluster of amino acid transporter genes. Mamm Genome 14, 114 125.
10. Berteloot A (1984). Characteristics of glutamic acid transport by rabbit intestinal brush-border membrane vesicles. Effects of Na+-, K+- and H+-gradients. Biochim Biophys Acta 775, 129 140.
11. Boll M, Daniel H & Gasnier B (2004). The SLC36 family: proton-coupled transporters for absorption of selected amino acids from extracellular and intracellular proteolysis. Pflugers Arch 447, 776 779.
12. Boll M, Foltz M, Anderson CMH, Oechsler C, Kottra G, Thwaites DT & Daniel H (2003). Substrate recognition by the mammalian proton-dependent amino acid transporter PAT1. Mol Membr Biol 20, 261 269.
13. Boll M, Foltz M, Rubio-Aliaga I, Kottra G & Daniel H (2002). Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters. J Biol Chem 277, 22966 22973.
14. Boll M, Markovich D, Weber WM, Korte H, Daniel H & Murer H (1994). Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, β-lactam antibiotics and ACE-inhibitors. Pflugers Arch 429, 146 149.
15. Boyd CAR & Ward MR (1982). A micro-electrode study of oligopeptide absorption by the small intestinal epithelium of Necturus maculosus. J Physiol 324, 411 428.
16. Brant SR, Yun CHC, Donowitz M & Tse CM (1995). Cloning, tissue distribution, and functional analysis of the human Na+/H+ exchanger isoform, NHE3. Am J Physiol Cell Physiol 269, C198 C206.
17. Bröer S (2006). The molecular basis of neutral amino acidurias. Acta Biomed 77 (Suppl. 3 6 8.
18. Bröer A, Klingel K, Kowalczuk S, Rasko JE, Cavanaugh J & Bröer S (2004). Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder. J Biol Chem 279, 24467 24476.
19. Bröer S, Schneider HP, Bröer A, Rahman B, Hamprecht B & Deitmer JW (1998). Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J 333, 167 174.
20. Bush DR (1993). Proton-coupled sugar and amino-acid transporters in plants. Annu Rev Plant Physiol Plant Mol Biol 44, 513 542.
21. Buyse M, Sitaraman SV, Liu X, Bado A & Merlin D (2002). Luminal leptin enhances CD147/MCT-1-mediated uptake of butyrate in the human intestinal cell line Caco2-BBE. J Biol Chem 277, 28182 28190.
22. Canonne-Hergaux F, Gruenheid S, Ponka P & Gros P (1999). Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93, 4406 4417.
23. Chen NH, Reith ME & Quick MW (2004). Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6. Pflugers Arch 447, 519 531.
24. Chen Z, Fei YJ, Anderson CMH, Wake KA, Miyauchi S, Huang W, Thwaites DT & Ganapathy V (2003a). Structure, function and immunolocalization of a proton-coupled amino acid transporter (hPAT1) in the human intestinal cell line Caco-2. J Physiol 546, 349 361.
25. Chen Z, Kennedy DJ, Wake KA, Zhuang L, Ganapathy V & Thwaites DT (2003b). Structure, tissue expression pattern, and function of the amino acid transporter rat PAT2. Biochem Biophys Res Commun 304, 747 754.
26. Christensen HN (1984). Naming plan for membrane transport systems for amino acids. Neurochem Res 9, 1757 1758.
27. Coady MJ, Chang MH, Charron FM, Plata C, Wallendorff B, Sah JF, Markowitz SD, Romero MF & Lapointe JY (2004). The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. J Physiol 557, 719 731.
28. Crane RK (1962). Hypothesis for mechanism of intestinal active transport of sugars. Fed Proc 21, 891 895.
29. Crane RK, Miller D & Bihler I (1961). The restrictions on possible mechanism of intestinal active transport of sugars. In Membrane Transport and Metabolism, ed. Kleinzeller A & Kotyk A, pp. 439 449. Academic Press, London.
30. Csáky TZ & Thale M (1960). Effect of ionic environment on intestinal sugar transport. J Physiol 151, 59 65.
31. Curran PF (1960). Na, Cl, and water transport by rat ileum in vitro. J Gen Physiol 43, 1137 1148.
32. Daniel H, Fett C & Kratz A (1989). Demonstration and modification of intervillous pH profiles in rat small intestine in vitro. Am J Physiol Gastrointest Liver Physiol 257, G489 G495.
33. Daniel H & Kottra G (2004). The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch 447, 610 618.
34. Daniel H, Neugebauer B, Kratz A & Rehner G (1985). Localization of acid microclimate along intestinal villi of rat jejunum. Am J Physiol Gastrointest Liver Physiol 248, G293 G298.
35. Daniel H & Rehner G (1986). Effect of metabolizable sugars on the mucosal surface pH of rat intestine. J Nutr 116, 768 777.
36. Dantzig AH & Bergin L (1990). Uptake of the cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2. Biochim Biophys Acta 1027, 211 217.
37. Delie F & Rubas W (1997). 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 14, 221 286.
38. Dixon KH, Lanpher BC, Chiu J, Kelley K & Cowan KH (1994). A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells. J Biol Chem 269, 17 20.
39. Dresser GK, Bailey DG, Leake BF, Schwarz UI, Dawson PA, Freeman DJ & Kim RB (2002). Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 71, 11 20.
40. Englund G, Rorsman F, Ronnblom A, Karlbom U, Lazorova L, Grasjo J, Kindmark A & Artursson P (2006). 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 29, 269 277.
41. Fei YJ, Kanai Y, Nussberger S, Ganapathy V, Leibach FH, Romero MF, Singh SK, Boron WF & Hediger MA (1994). Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368, 563 566.
42. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD & Andrews NC (1998). Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci U S A 95, 1148 1153.
43. Fleming MD, Trenor CC, Su MA, Foernzler D, Beier DR, Dietrich WF & Andrews NC (1997). Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16, 383 386.
44. Foltz M, Boll M, Raschka L, Kottra G & Daniel H (2004a). A novel bifunctionality: PAT1 and PAT2 mediate electrogenic proton/amino acid and electroneutral proton/fatty acid symport. FASEB J 18, 1758 1760.
45. Foltz M, Oechsler C, Boll M, Kottra G & Daniel H (2004b). Substrate specificity and transport mode of the proton-dependent amino acid transporter mPAT2. Eur J Biochem 271, 3340 3347.
46. Freeman TC, Bentsen BS, Thwaites DT & Simmons NL (1995). H+/di-tripeptide transporter (PepT1) expression in the rabbit intestine. Pflugers Arch 430, 394 400.
47. Freeman TC, Collins AJ, Heavens RP & Tivey DR (1993). Genetic regulation of enterocyte function: a quantitative in situ hybridisation study of lactase-phlorizin hydrolase and Na+-glucose cotransporter mRNAs in rabbit small intestine. Pflugers Arch 422, 570 576.
48. Ganapathy V, Burckhardt G & Leibach FH (1984). Characteristics of glycylsarcosine transport in rabbit intestinal brush-border membrane vesicles. J Biol Chem 259, 8954 8959.
49. Ganapathy V, Gopal E, Miyauchi S & Prasad PD (2005). Biological functions of SLC5A8, a candidate tumour suppressor. Biochem Soc Trans 33, 237 240.
50. Ganapathy V, Gupta N & Martindale RG (2006). Protein digestion and absorption. In Physiology of the Gastrointestinal Tract, ed. Johnson LR, pp. 1667 1692. Elsevier, San Diego.
51. Ganapathy V & Leibach FH (1983). Role of pH gradient and membrane potential in dipeptide transport in intestinal and renal brush-border membrane vesicles from the rabbit. J Biol Chem 258, 14189 14192.
52. Ganapathy V & Leibach FH (1985). Is intestinal peptide transport energized by a proton gradient? Am J Physiol Gastrointest Liver Physiol 249, G153 G160.
53. Ganapathy V, Smith SB & Prasad PD (2004). SLC19: the folate/thiamine transporter family. Pflugers Arch 447, 641 646.
54. Garcia CK, Brown MS, Pathak RK & Goldstein JL (1995). cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. J Biol Chem 270, 1843 1849.
55. Garcia CK, Goldstein JL, Pathak RK, Anderson RG & Brown MS (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76, 865 873.
56. Gill RK, Saksena S, Alrefai WA, Sarwar Z, Goldstein JL, Carroll RE, Ramaswamy K & Dudeja PK (2005). Expression and membrane localization of MCT isoforms along the length of the human intestine. Am J Physiol Cell Physiol 289, C846 C852.
57. Goberdhan DCI, Meredith D, Boyd CAR & Wilson C (2005). PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Development 132, 2365 2375.
58. Gopal E, Fei YJ, Sugawara M, Miyauchi S, Zhuang L, Martin P, Smith SB, Prasad PD & Ganapathy V (2004). Expression of slc5a8 in kidney and its role in Na+-coupled transport of lactate. J Biol Chem 279, 44522 44532.
59. Gray JH, Owen RP & Giacomini KM (2004). The concentrative nucleoside transporter family, SLC28. Pflugers Arch 447, 728 734.
60. 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 (2006). Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clin Pharmacol Ther 80, 607 620.
61. Gunshin H, Fujiwara Y, Custodio AO, Direnzo C, Robine S & Andrews NC (2005). Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest 115, 1258 1266.
62. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL & Hediger MA (1997). Cloning and characterization of a mammalian proton-coupled metalion transporter. Nature 388, 482 488.
63. Hadjiagapiou C, Schmidt L, Dudeja PK, Layden TJ & Ramaswamy K (2000). Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1. Am J Physiol Gastrointest Liver Physiol 279, G775 G780.
64. Hagenbuch B & Dawson P (2004). The sodium bile salt cotransport family SLC10. Pflugers Arch 447, 566 570.
65. Hagenbuch B & Meier PJ (2003). The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 1609, 1 18.
66. Hagenbuch B & Meier PJ (2004). Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch 447, 653 665.
67. Halestrap AP & Meredith D (2004). The SLC16 gene family - from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447, 619 628.
68. Harig JM, Rajendran VM, Barry JA & Ramaswamy K (1987). Transport characteristics of l-glutamate in human jejunal brush-border membrane vesicles. Biochim Biophys Acta 903, 358 364.
69. Hatanaka T, Haramura M, Fei YJ, Miyauchi S, Bridges CC, Ganapathy PS, Smith SB, Ganapathy V & Ganapathy ME (2004). 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 308, 1138 1147.
70. Hediger MA (1994). Structure, function and evolution of solute transporters in prokaryotes and eukaryotes. J Exp Biol 196, 15 49.
71. Hediger MA, Coady MJ, Ikeda TS & Wright EM (1987). Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. Nature 330, 379 381.
72. Henderson PJF (1990). Proton-linked sugar transport systems in bacteria. J Bioenerg Biomembr 22, 525 569.
73. Hirayama BA, Loo DD & Wright EM (1994). Protons drive sugar transport through the Na+/glucose cotransporter (SGLT1). J Biol Chem 269, 21407 21410.
74. Hogben CAM, Tocco DJ, Brodie BB & Schanker LS (1959). On the mechanism of intestinal absorption of drugs. J Pharmacol Exp Ther 125, 275 282.
75. Hoogerwerf WA, Tsao SC, Devuyst O, Levine SA, Yun CH, Yip JW, Cohen ME, Wilson PD, Lazenby AJ, Tse CM & Donowitz M (1996). NHE2 and NHE3 are human and rabbit intestinal brush-border proteins. Am J Physiol Gastrointest Liver Physiol 270, G29 G41.
76. Hopfer U, Nelson K, Perrotto J & Isselbacher KJ (1973). Glucose transport in isolated brush border membrane from rat small intestine. J Biol Chem 248, 25 32.
77. Hoshi T, Takuwa N, Abe M & Tajima A (1986). Hydrogen ion-coupled transport of d-glucose by phlorizin-sensitive sugar carrier in intestinal brush-border membranes. Biochim Biophys Acta 861, 483 488.
78. Hwang ES, Hirayama BA & Wright EM (1991). Distribution of the SGLT1 Na+/glucose cotransporter and mRNA along the crypt-villus axis of rabbit small intestine. Biochem Biophys Res Commun 181, 1208 1217.
79. Iñigo C, Barber A & Lostao MP (2006). Na+ and pH dependence of proline and β-alanine absorption in rat small intestine. Acta Physiol (Oxf) 186, 271 278.
80. Inui K, Yamamoto M & Saito H (1992). 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 261, 195 201.
81. Iwanaga T, Goto M & Watanabe M (2005). Cellular distribution of glutamate transporters in the gastrointestinal tract of mice: an immunohistochemical and in situ hybridization approach. Biomed Res 26, 271 278.
82. Iwanaga T, Takebe K, Kato I, Karaki S & Kuwahara A (2006). Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8. Biomed Res 27, 243 254.
83. Kanai Y & Hediger MA (1992). Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467 471.
84. Kanai Y & Hediger MA (2004). The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflugers Arch 447, 469 479.
85. Kanai Y, Stelzner M, Nussberger S, Khawaja S, Hebert SC, Smith CP & Hediger MA (1994). The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport. J Biol Chem 269, 20599 20606.
86. Kennedy DJ, Gatfield KM, Winpenny JP, Ganapathy V & Thwaites DT (2005a). Substrate specificity and functional characterisation of the H+/amino acid transporter rat PAT2 (Slc36a2). Br J Pharmacol 144, 28 41.
87. Kennedy DJ, Leibach FH, Ganapathy V & Thwaites DT (2002). Optimal absorptive transport of the dipeptide glycylsarcosine is dependent on functional Na+/H+ exchange activity. Pflugers Arch 445, 139 146.
88. Kennedy DJ, Raldua D & Thwaites DT (2005b). 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 62, 1621 1631.
89. Khoursandi S, Scharlau D, Herter P, Kuhnen C, Martin D, Kinne RK & Kipp H (2004). Different modes of sodium-d-glucose cotransporter-mediated d-glucose uptake regulation in Caco-2 cells. Am J Physiol Cell Physiol 287, C1041 C1047.
90. Kim CM, Goldstein JL & Brown MS (1992). 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 267, 23113 23121.
91. Klomp AE, Tops BB, Van Denberg IE, Berger R & Klomp LW (2002). Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1). Biochem J 364, 497 505.
92. Kneuer C & Honscha W (2004). The H+-dependent reduced folate carrier 1 of humans and the sodium-dependent methotrexate carrier-1 of the rat are orthologs. FEBS Lett 566, 83 86.
93. Kobayashi D, Nozawa T, Imai K, Nezu J, Tsuji A & Tamai I (2003). Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther 306, 703 708.
94. Kowalczuk S, Bröer A, Munzinger M, Tietze N, Klingel K & Bröer S (2005). Molecular cloning of the mouse IMINO system: an Na+- and Cl - dependent proline transporter. Biochem J 386, 417 422.
95. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ & Hagenbuch B (2001). Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 120, 525 533.
96. Kumar CK, Nguyen TT, Gonzales FB & Said HM (1998). Comparison of intestinal folate carrier clone in IEC-6 cells and in Xenopus oocytes. Am J Physiol Cell Physiol 274, C289 C294.
97. Kuo YM, Gybina AA, Pyatskowit JW, Gitschier J & Prohaska JR (2006). Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status. J Nutr 136, 21 26.
98. Lee J, Pena MM, Nose Y & Thiele DJ (2002). Biochemical characterization of the human copper transporter Ctr1. J Biol Chem 277, 4380 4387.
99. Liang R, Fei YJ, Prasad PD, Ramamoorthy S, Han H, Yang-Feng TL, Hediger MA, Ganapathy V & Leibach FH (1995). Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization. J Biol Chem 270, 6456 6463.
100. Lucas ML, Lei FH & Blair JA (1980). The influence of buffer pH, glucose and sodium ion concentration on the acid microclimate in rat proximal jejunum in vitro. Pflugers Arch 385, 137 142.
101. Lucas ML, Schneider W, Haberich FJ & Blair JA (1975). Direct measurement by pH-microelectrode of the pH microclimate in rat proximal jejunum. Proc R Soc Lond B Biol Sci 192, 39 48.
102. McEwan GTA, Daniel H, Fett C, Burgess MN & Lucas ML (1988). 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 Biol Sci 234, 219 237.
103. Mackenzie B & Garrick MD (2005). Iron Imports. II. Iron uptake at the apical membrane in the intestine. Am J Physiol Gastrointest Liver Physiol 289, G981 G986.
104. Mackenzie B & Hediger MA (2004). SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1. Pflugers Arch 447, 571 579.
105. McKie AT, Kusel M, McEwan GTA & Lucas ML (1988). 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 971, 325 331.
106. Maenz DD, Chenu C, Breton S & Berteloot A (1992). pH-dependent heterogeneity of acidic amino acid transport in rabbit jejunal brush border membrane vesicles. J Biol Chem 267, 1510 1516.
107. Markovich D & Murer H (2004). The SLC13 gene family of sodium sulphate/carboxylate cotransporters. Pflugers Arch 447, 594 602.
108. Martel F, Monteiro R & Lemos C (2003). 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 306, 355 362.
109. Martín-Venegas R, Rodriguez-Lagunas MJ, Geraert PA & Ferrer R (2007). Monocarboxylate transporter 1 mediates dl-2-Hydroxy-(4-methylthio) butanoic acid transport across the apical membrane of Caco-2 cell monolayers. J Nutr 137, 49 54.
110. Mason JB, Shoda R, Haskell M, Selhub J & Rosenberg IH (1990). Carrier affinity as a mechanism for the pH dependence of folate transport in the small intestine. Biochim Biophys Acta 1024, 331 335.
111. Metzner L, Kalbitz J & Brandsch M (2004). Transport of pharmacologically active proline derivatives by the human proton-coupled amino acid transporter hPAT1. J Pharmacol Exp Ther 309, 28 35.
112. Metzner L, Kottra G, Neubert K, Daniel H & Brandsch M (2005). Serotonin, l-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1. FASEB J 19, 1468 1473.
113. Mitchell P (1961). Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191, 144 148.
114. Mitchell P (1963). Molecule, group and electron translocation through natural membranes. Biochem Soc Symp 22, 142 169.
115. Mitchell P (1973). Performance and conservation of osmotic work by proton-coupled solute porter systems. Bioenergetics 4, 63 91.
116. Miyauchi S, Abbot EL, Zhuang L, Subramanian R, Ganapathy V & Thwaites DT (2005). 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 22, 549 559.
117. Murer H, Forster I & Biber J (2004). The sodium phosphate cotransporter family SLC34. Pflugers Arch 447, 763 767.
118. Murer H, Hopfer U & Kinne R (1976). Sodium/proton antiport in brush-border membrane vesicles isolated from rat small intestine and kidney. Biochem J 154, 597 604.
119. Nguyen TT, Dyer DL, Dunning DD, Rubin SA, Grant KE & Said HM (1997). Human intestinal folate transport: cloning, expression, and distribution of complementary RNA. Gastroenterology 112, 783 791.
120. Nose Y, Kim BE & Thiele DJ (2006). Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. Cell Metab 4, 235 244.
121. Nozawa T, Imai K, Nezu J, Tsuji A & Tamai I (2004). Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther 308, 438 445.
122. Nozawa T, Nakajima M, Tamai I, Noda K, Nezu JI, Sai Y, Tsuji A & Yokoi T (2002). 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 302, 804 813.
123. Orlowski J (1993). 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 268, 16369 16377.
124. Petris MJ (2004). The SLC31 (Ctr) copper transporter family. Pflugers Arch 447, 752 755.
125. Prasad PD, Ramamoorthy S, Leibach FH & Ganapathy V (1995). Molecular cloning of the human placental folate transporter. Biochem Biophys Res Commun 206, 681 687.
126. Price NT, Jackson VN & Halestrap AP (1998). Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. Biochem J 329, 321 328.
127. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH & Goldman ID (2006). Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127, 917 928.
128. Quick M, Loo DD & Wright EM (2001). Neutralization of a conserved amino acid residue in the human Na+/glucose transporter (hSGLT1) generates a glucose-gated H+ channel. J Biol Chem 276, 1728 1734.
129. Ricklis E & Quastel JH (1958). Effects of cations on sugar absorption by isolated surviving guinea pig intestine. Can J Biochem Physiol 36, 347 362.
130. Riggs TR, Walker LM & Christensen HN (1958). Potassium migration and amino acid transport. J Biol Chem 233, 1479 1484.
131. Ritzhaupt A, Wood IS, Ellis A, Hosie KB & Shirazi-Beechey SP (1998). 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 513, 719 732.
132. Rome S, Barbot L, Windsor E, Kapel N, Tricottet V, Huneau JF, Reynes M, Gobert JG & Tome D (2002). The regionalization of PepT1, NBAT and EAAC1 transporters in the small intestine of rats are unchanged from birth to adulthood. J Nutr 132, 1009 1011.
133. Rubio-Aliaga I, Boll M, Vogt-Weisenhorn DM, Foltz M, Kottra G & Daniel H (2004). The proton/amino acid cotransporter PAT2 is expressed in neurons with a different subcellular localization than its paralog PAT1. J Biol Chem 279, 2754 2760.
134. Rubio-Aliaga I & Daniel H (2002). Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol Sci 23, 434 440.
135. Sagné C, Agulhon C, Ravassard P, Darmon M, Hamon M, El Mestikawy S, Gasnier B & Giros B (2001). Identification and characterization of a lysosomal transporter for small neutral amino acids. Proc Natl Acad Sci U S A 98, 7206 7211.
136. Sai Y, Kaneko Y, Ito S, Mitsuoka K, Kato Y, Tamai I, Artursson P & Tsuji A (2006). 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 34, 1423 1431.
137. Said HM, Chatterjee N, Haq RU, Subramanian VS, Ortiz A, Matherly LH, Sirotnak FM, Halsted C & Rubin SA (2000). Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency. Am J Physiol Cell Physiol 279, C1889 C1895.
138. Said HM, Ghishan FK & Redha R (1987). Folate transport by human intestinal brush-border membrane vesicles. Am J Physiol Cell Physiol 252, G229 G236.
139. Said HM, Nguyen TT, Dyer DL, Cowan KH & Rubin SA (1996). Intestinal folate transport: identification of a cDNA involved in folate transport and the functional expression and distribution of its mRNA. Biochim Biophys Acta 1281, 164 172.
140. Satoh H, Yamashita F, Tsujimoto M, Murakami H, Koyabu N, Ohtani H & Sawada Y (2005). Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 33, 518 523.
141. Schanker LS, Tocco DJ, Brodie BB & Hogben CAM (1958). Absorption of drugs from the rat small intestine. J Pharmacol Exp Ther 123, 81 88.
142. Schron CM, Washington C & Blitzer BL (1985). 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 76, 2030 2033.
143. Schultz SG & Zalusky R (1964). Ion transport in isolated rabbit ileum. II. The interaction between active sodium and active sugar transport. J Gen Physiol 47, 1043 1059.
144. Seithel A, Karlsson J, Hilgendorf C, Bjorquist A & Ungell AL (2006). 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 28, 291 299.
145. Selhub J & Rosenberg IH (1981). Folate transport in isolated brush border membrane vesicles from rat intestine. J Biol Chem 256, 4489 4493.
146. Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, Khan Y, Warley A, McCann FE, Hider RC, Frazer DM, Anderson GJ, Vulpe CD, Simpson RJ & McKie AT (2005). Identification of an intestinal heme transporter. Cell 122, 789 801.
147. Shiau YF, Fernandez P, Jackson MJ & McMonagle S (1985). Mechanisms maintaining a low-pH microclimate in the intestine. Am J Physiol Gastrointest Liver Physiol 248, G608 G617.
148. Shimada T (1987). Factors affecting the microclimate pH in rat jejunum. J Physiol 392, 113 127.
149. Shimada T & Hoshi T (1988). 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 937, 328 334.
150. Simanjuntak MT, Tamai I, Terasaki T & Tsuji A (1990). Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport. J Pharmacobiodyn 13, 301 309.
151. Skulachev VP (1994). Chemiosmotic concept of the membrane bioenergetics: what is already clear and what is still waiting for elucidation? J Bioenerg Biomembr 26, 589 598.
152. Smith MW, Turvey A & Freeman TC (1992). Appearance of phloridzin-sensitive glucose transport is not controlled at mRNA level in rabbit jejunal enterocytes. Exp Physiol 77, 525 528.
153. Srinivas SR, Gopal E, Zhuang L, Itagaki S, Martin PM, Fei YJ, Ganapathy V & Prasad PD (2005). Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2). Biochem J 392, 655 664.
154. Stein J, Zores M & Schroder O (2000). Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism. Eur J Nutr 39, 121 125.
155. Su MA, Trenor CC, Fleming JC, Fleming MD & Andrews NC (1998). The G185R mutation disrupts function of the iron transporter Nramp2. Blood 92, 2157 2163.
156. Takanaga H, Mackenzie B & Hediger MA (2004). Sodium-dependent ascorbic acid transporter family SLC23. Pflugers Arch 447, 677 682.
157. Takanaga H, Mackenzie B, Suzuki Y & Hediger MA (2005). Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino. J Biol Chem 280, 8974 8984.
158. Takanaga H, Maeda H, Yabuuchi H, Tamai I, Higashida H & Tsuji A (1996). Nicotinic acid transport mediated by pH-dependent anion antiporter and proton cotransporter in rabbit intestinal brush-border membrane. J Pharm Pharmacol 48, 1073 1077.
159. Takanaga H, Tamai I, Inaba S, Sai Y, Higashida H, Yamamoto H & Tsuji A (1995). cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter. Biochem Biophys Res Commun 217, 370 377.
160. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M & Tsuji A (2000). Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun 273, 251 260.
161. Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S & Tsuji A (1999). Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol 51, 1113 1121.
162. Tamai I, Takanaga H, Maeda H, Ogihara T, Yoneda M & Tsuji A (1995a). Proton-cotransport of pravastatin across intestinal brush-border membrane. Pharm Res 12, 1727 1732.
163. Tamai I, Takanaga H, Maeda H, Sai Y, Ogihara T, Higashida H & Tsuji A (1995b). Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids. Biochem Biophys Res Commun 214, 482 489.
164. Tandy S, Williams M, Leggett A, Lopez-Jimenez M, Dedes M, Ramesh B, Srai SK & Sharp P (2000). Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J Biol Chem 275, 1023 1029.
165. Thwaites DT & Anderson CMH (2007). Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1. Biochim Biophys Acta 1768, 179 197.
166. Thwaites DT, Armstrong G, Hirst BH & Simmons NL (1995a). d-Cycloserine transport in human intestinal epithelial (Caco-2) cells: mediation by a H+-coupled amino acid transporter. Br J Pharmacol 115, 761 766.
167. Thwaites DT, Basterfield L, McCleave PMJ, Carter SM & Simmons NL (2000). γ-Aminobutyric acid (GABA) transport across human intestinal epithelial (Caco-2) cell monolayers. Br J Pharmacol 129, 457 464.
168. Thwaites DT, Brown CDA, Hirst BH & Simmons NL (1993a). Transepithelial glycylsarcosine transport in intestinal Caco-2 cells mediated by expression of H+-coupled carriers at both apical and basal membranes. J Biol Chem 268, 7640 7642.
169. Thwaites DT, Brown CDA, Hirst BH & Simmons NL (1993b). H+-coupled dipeptide (glycylsarcosine) transport across apical and basal borders of human intestinal Caco-2 cell monolayers display distinctive characteristics. Biochim Biophys Acta 1151, 237 245.
170. Thwaites DT, Ford D, Glanville M & Simmons NL (1999). H+/solute-induced intracellular acidification leads to selective activation of apical Na+/H+ exchange in human intestinal epithelial cells. J Clin Invest 104, 629 635.
171. Thwaites DT, Hirst BH & Simmons NL (1993c). 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 194, 432 438.
172. Thwaites DT, Hirst BH & Simmons NL (1994a). Substrate specificity of the di/tripeptide transporter in human intestinal epithelia (Caco-2): identification of substrates that undergo H+-coupled absorption. Br J Pharmacol 113, 1050 1056.
173. Thwaites DT, Kennedy DJ, Raldua D, Anderson CMH, Mendoza ME, Bladen CL & Simmons NL (2002). H+/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na+/H+ exchanger. Gastroenterology 122, 1322 1333.
174. Thwaites DT, McEwan GTA, Brown CDA, Hirst BH & Simmons NL (1993d). Na+-independent, H+-coupled transepithelial β-alanine absorption by human intestinal Caco-2 cell monolayers. J Biol Chem 268, 18438 18441.
175. Thwaites DT, McEwan GTA, Brown CDA, Hirst BH & Simmons NL (1994b). l-Alanine absorption in human intestinal Caco-2 cells driven by the proton electrochemical gradient. J Membr Biol 140, 143 151.
176. Thwaites DT, McEwan GTA, Cook MJ, Hirst BH & Simmons NL (1993e). H+-coupled (Na+-independent) proline transport in human intestinal (Caco-2) epithelial cell monolayers. FEBS Lett 333, 78 82.
177. Thwaites DT, McEwan GTA, Hirst BH & Simmons NL (1993f). Transepithelial dipeptide (glycylsarcosine) transport across epithelial monolayers of human Caco-2 cells is rheogenic. Pflugers Arch 425, 178 180.
178. Thwaites DT, McEwan GTA, Hirst BH & Simmons NL (1995b). H+-coupled α-methylaminoisobutyric acid transport in human intestinal Caco-2 cells. Biochim Biophys Acta 1234, 111 118.
179. Thwaites DT, McEwan GTA & Simmons NL (1995c). The role of the proton electrochemical gradient in the transepithelial absorption of amino acids by human intestinal Caco-2 cell monolayers. J Membr Biol 145, 245 256.
180. Thwaites DT & Stevens BC (1999). H+/zwitterionic amino acid symport at the brush-border membrane of human intestinal epithelial (CACO-2) cells. Exp Physiol 84, 275 284.
181. Tiruppathi C, Balkovetz DF, Ganapathy V, Miyamoto Y & Leibach FH (1988). 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 256, 219 223.
182. Tsuchiya T & Wilson TH (1978). Cation-sugar cotransport in the melibiose transport system of Escherichia coli. Membr Biochem 2, 63 79.
183. Vidal S, Belouchi AM, Cellier M, Beatty B & Gros P (1995). Cloning and characterization of a second human NRAMP gene on chromosome 12q13. Mamm Genome 6, 224 230.
184. Vincent ML, Russell RM & Sasak V (1985). 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 39, 355 360.
185. Walker D, Thwaites DT, Simmons NL, Gilbert HJ & Hirst BH (1998). Substrate upregulation of the human small intestinal peptide transporter, hPepT1. J Physiol 507, 697 706.
186. Wang Y, Rajgopal A, Goldman ID & Zhao R (2005). 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 Cell Physiol 288, C65 C71.
187. Wang Y, Zhao R & Goldman ID (2004). 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 10, 6256 6264.
188. Wang Y, Zhao R, Russell RG & Goldman ID (2001). Localization of the murine reduced folate carrier as assessed by immunohistochemical analysis. Biochim Biophys Acta 1513, 49 54.
189. West IC (1970). Lactose transport coupled to proton movements in Escherichia coli. Biochem Biophys Res Commun 41, 655 661.
190. West I & Mitchell P (1972). Proton-coupled β-galactoside translocation in non-metabolizing Escherichia coli. Bioenergetics 3, 445 462.
191. West IC & Mitchell P (1973). Stoicheiometry of lactose-protein symport across the plasma membrane of Escherichia coli. Biochem J 132, 587 592.
192. Wipf D, Ludewig U, Tegeder M, Rentsch D, Koch W & Frommer WB (2002). Conservation of amino acid transporters in fungi, plants and animals. Trends Biochem Sci 27, 139 147.
193. Wright EM, Loo DD, Hirayama BA & Turk E (2004). Surprising versatility of Na+-glucose cotransporters: SLC5. Physiology (Bethesda) 19, 370 376.
194. Wright EM & Turk E (2004). The sodium/glucose cotransport family SLC5. Pflugers Arch 447, 510 518.
195. Wright EM, Turk E, Zabel B, Mundlos S & Dyer J (1991). Molecular genetics of intestinal glucose transport. J Clin Invest 88, 1435 1440.
196. Wu X, Whitfield LR & Stewart BH (2000). Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton- monocarboxylic acid co-transporter. Pharm Res 17, 209 215.
197. Yoshida A, Takata K, Kasahara T, Aoyagi T, Saito S & Hirano H (1995). Immunohistochemical localization of Na+-dependent glucose transporter in the rat digestive tract. Histochem J 27, 420 426.
198. Zerangue N & Kavanaugh MP (1996a). Flux coupling in a neuronal glutamate transporter. Nature 383, 634 637.
199. Zerangue N & Kavanaugh MP (1996b). Interaction of l-cysteine with a human excitatory amino acid transporter. J Physiol 493, 419 423.
200. Zhao R, Gao F & Goldman ID (2002). Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells. Am J Physiol Cell Physiol 282, C1512 C1517.
201. Zhao R & Goldman ID (2007). The molecular identity and characterization of a proton-coupled folate transporter PCFT; biological ramifications and impact on the activity of permetrexed. Cancer Metastasis Rev 26, 129 139.