Hijacking solute carriers for proton-coupled drug transport

Physiology

Volumn 25, Issue 6, 2010, Pages 364-377

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

^a NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIPORTER; COTRANSPORTER; DRUG; PROTON;

ANIMAL; HUMAN; KIDNEY PROXIMAL TUBULE; METABOLISM; NEOPLASM; PH; REVIEW; SMALL INTESTINE; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; ANTIPORTERS; BIOLOGICAL TRANSPORT; HUMANS; HYDROGEN-ION CONCENTRATION; INTESTINE, SMALL; KIDNEY TUBULES, PROXIMAL; NEOPLASMS; PHARMACEUTICAL PREPARATIONS; PROTONS; SYMPORTERS;

EID: 78651253877     PISSN: 15489213     EISSN: 15489221     Source Type: Journal    
DOI: 10.1152/physiol.00027.2010     Document Type: Review

References (133)

1. +-coupled amino acid transporter hPAT1. Br J Pharmacol 147:298-306, 2006.
2. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma H, Ito S, Matsuno S. LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology 120:1689-1699, 2001.
3. +/amino acid transporter 1 (PAT1) is the imino acid carrier: an intestinal nutrient/drug transporter in human and rat. Gastroenterology 127:1410-1422, 2004.
4. - dependent TauT (SLC6A6). J Physiol 587:731-744, 2009.
5. +-coupled nutrient carriers coexpressed in the small intestine. J Pharmacol Exp Ther 332:220-228, 2010.
6. Anderson C M H, 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 138:564-573, 2003.
7. +-coupled amino acid transporter hPAT1 (SLC36A1). J Cell Physiol 204:604-613, 2005.
8. Anderson C M H, Thwaites DT. Regulation of intestinal hPepT1 (SLC15A1) activity by phosphodiesterase inhibitors is via inhibition of NHE3 (SLC9A3). Biochim Biophys Acta 1768:1822-1829, 2007.
9. Bahn A, Hagos Y, Reuter S, Balen D, Brzica H, Krick W, Burckhardt BC, Sabolic I, Burckhardt G. Identification of a new urate and high affinity nicotinate transporter, hOAT10 (SLC22A13). J Biol Chem 283:16332-16341, 2008.
10. Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, Sun L, Tellez J, Ritzel M W L, Claycomb WC, Cass CE, Young JD, Billeter-Clark R, Boyett MR, Baldwin SA. Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ Res 99:510-519, 2006.
11. Beauchamp LM, Orr GF, de Miranda P, Burnette T, Krenitsky TA. Amino acid ester prodrugs of acyclovir. Antiviral Chem Chemother 3:157-164, 1992.
12. Boll M, Foltz M, Anderson C M H, Oechsler C, Kottra G, Thwaites DT, Daniel H. Substrate recognition by the mammalian proton-dependent amino acid transporter PAT1. Mol Membr Biol 20:261-269, 2003.
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 277:22966-22973, 2002.
14. Boll M, Herget M, Wagener M, Weber WM, Markovich D, Biber J, Clauss W, Murer H, Daniel H. Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc Natl Acad Sci USA 93:284-289, 1996.
15. Brandsch M. Transport of drugs by proton-coupled peptide transporters: pearls and pitfalls. Expert Opin Drug Metab Toxicol 5:887-905, 2009.
16. 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 333:167-174, 1998.
17. Bunch L, Erichsen MN, Jensen AA. Excitatory amino acid transporters as potential drug targets. Expert Opin Ther Targets 13:719-731, 2009.
18. Chaudhry FA, Edwards RH, Fonnum F. Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances. Annu Rev Pharmacol Toxicol 48:277-301, 2008.
19. Chen Z, Fei YJ, Anderson C M H, 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 546:349-361, 2003.
20. Chesler M. Regulation and modulation of pH in the brain. Physiol Rev 83:1183-1221, 2003.
21. Daniel H, Fett C, Kratz A. Demonstration and modification of intervillous pH profiles in rat small intestine in vitro. Am J Physiol Gastrointest Liver Physiol 257: G489-G495, 1989.
22. De Hemptinne A, Marrannes R, Vanheel B. Surface pH and control of intracellular pH in cardiac and skeletal muscle. Can J Physiol Pharmacol 65:970-977, 1987.
23. Deitmer JW, Rose CR. pH regulation and proton signalling by glial cells. Prog Neurobiol 48:73-103, 1996.
24. Döring F, Walter J, Will J, Focking M, Boll M, Amasheh S, Clauss W, Daniel H. Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest 101:2761-2767, 1998.
25. Eiden LE, Schafer M K H, Weihe E, Schutz B. The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretions of monoamines and acetylcholine. Pflügers Arch 447:636-640, 2004.
26. Enerson BE, Drewes LR. Molecular features, regulation, and function of monocarboxylate transporters: implications for drug delivery. J Pharm Sci 92:1531-1544, 2003.
27. +-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma. Mol Pharmacol 70:2108-2115, 2006.
28. 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 368:563-566, 1994. (Pubitemid 24118776)
29. 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 18:1758-1760, 2004.
30. +/di- tripeptide transporter (PepT1) expression in the rabbit intestine. Pflügers Arch 430:394-400, 1995.
31. Ganapathy ME, Huang W, Ganapathy V, Leibach FH. Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun 246:470-475, 1998.
32. Ganapathy V, Leibach FH. Is intestinal peptide transport energized by a proton gradient? Am J Physiol Gastrointest Liver Physiol 249: G153-G160, 1985.
33. 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 258:14189-14192, 1983.
34. Ganapathy V, Thangaraju M, Prasad PD. Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121:29-40, 2009.
35. Garcia CK, Goldstein JL, Pathak RK, Anderson R G W, Brown MS. Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76:865-873, 1994.
36. Gerwick LE, Seetharaman K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res 56:1194-1198, 1996.
37. 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 Cell Physiol 289: C846-C852, 2005.
38. Gonzalez DE, Covitz K M Y, Sadee W, Mrsny RJ. An oligopeptide transporter is expressed at high levels in the pancreatic carcinoma cell lines AsPc-1 and Capan-2. Cancer Res 58:519-525, 1998.
39. Hagenbuch B, Gui C. Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 38:778-801, 2008.
40. Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins. Pflügers Arch 447:465-468, 2004.
41. Hogben C A M, Tocco DJ, Brodie BB, Schanker LS. On the mechanism of intestinal absorption of drugs. J Pharmacol Exp Ther 125:275-282, 1959.
42. Holohan PD, Ross CR. Mechanisms of organic cation transport in kidney plasma membrane vesicles: 2. ApH studies. J Pharmacol Exp Ther 216:294-298, 1981.
43. Horne DW, Reed KA, Hoefs J, Said HM. 5-Methyltetrahydrofolate transport in basolateral membrane vesicles from human liver. Am J Clin Nutr 58:80-84, 1993.
44. Ichikawa M, Kato Y, Sawada Y, Iga T, Fuwa T, Hanano M, Sugiyama Y. Effect of perfusate on the influx of 5-5'-dimethyl-oxazolidine-2, 4-dione and dissociation of epidermal growth factor from the cell-surface receptor: the existence of the proton diffusion barrier in the Disse space. J Hepatol 20:190-200, 1994.
45. Inoue K, Nakai Y, Ueda S, Kamigaso S, Ohta KY, Hatakeyama M, Hayashi Y, Otagiri M, Yuasa H. Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model. Am J Physiol Gastrointest Liver Physiol 294: G660-G668, 2008.
46. Inoue M, Terada T, Okuda M, Inui K. Regulation of human peptide transporter 1 (PEPT1) in gastric cancer cells by anticancer drugs. Cancer Lett 230:72-80, 2005.
47. Kamal MA, Keep RF, Smith DE. Role and relevance of PEPT2 in drug disposition, dynamics and toxicity. Drug Metab Pharmacokinet 23:236-242, 2008.
48. + exchanger: a target for cardiac therapeutic intervention. Curr Drug Targets Cardiovasc Haematol Disord 5:323-335, 2005.
49. Kato Y, Kubo Y, Iwata D, Kato S, Sudo T, Sugiura T, Kagaya T, Wakayama T, Hirayama A, Sugimoto M, Sugihara K, Kaneko S, Soga T, Asano M, Tomita M, Matsui T, Wada M, Tsuji A. Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res 27:832-840, 2010.
50. + exchange activity. Pflügers Arch 445:139-146, 2002.
51. 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 62:1621-1631, 2005.
52. +-peptide cotransport in the human bile duct epithelium cell line SK-ChA-1. Am J Physiol Gastrointest Liver Physiol 283: G222-G229, 2002.
53. 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 306:703-708, 2003.
54. Larsen M, Holm R, Jensen KG, Brodin B, Nielsen CU. Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo following co-administration of L-tryptophan. Br J Pharmacol 157:1380-1389, 2009.
55. Leuthold S, Hagenbuch B, Mohebbi N, Wagner CA, Meier PJ, Stieger B. Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters. Am J Physiol Cell Physiol 296: C570-C582, 2009.
56. +/peptide cotransporter. Cloning, functional expression, and chromosomal localization. J Biol Chem 270:6456-6463, 1995.
57. Lin CJ, Smith DE. Glycylsarcosine uptake in rabbit renal brush border membrane vesicles isolated from outer cortex or outer medulla: evidence for heterologous distribution of oligopeptide transporters. AAPS Pharm Sci 1: E1, 1999.
58. +/peptide cotransporter family, from human kidney. Biochim Biophys Acta 1235:461-466, 1995.
59. Lucas ML, Cooper BT, Lei FH, Johnson IT, Holmes G K T, Blair JA, Cooke WT. Acid microclimate in celiac and Crohn's disease: a model for folate malabsorption. Gut 19:735-742, 1978.
60. 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 192:39-48, 1975.
61. McEwan G T A, Lucas ML. The effect of E. coliSTa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo. Br J Pharmacol 101:937-943, 1990.
62. Maeda S, Takano M, Okano T, Ohaka K, Inui K, Hori R. Transport of organic cation in renal brushborder membrane from rats with renal ischemic injury. Biochim Biophys Acta 1150:103-110, 1993.
63. +/organic cation antiporters, kidneyspecific multidrug and toxin extrusion 2. J Am Soc Nephrol 17:2127-2135, 2006.
64. Matherly LH, Hou Z, Deng Y. Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Met Rev 26:111-128, 2007.
65. Matthews DM. Peptide transport: the concept and its development. In: Advances in the Biosciences Volume 63, edited by Schowen RI, and, Barth A. New York: Pergamon Press, 1987, p. 83-90.
66. Meredith D, Christian HC. The SLC16 monocarboxylate transporter family. Xenobiotica 38:1072-1106, 2008.
67. Metzner L, Dorn M, Markwardt F, Brandsch M. The orally active antihyperglycemic drug β-guanidinopropionicacid is transported by the human proton-coupled amino acid transporter hPAT1. Mol Pharm 6:1006-1011, 2009.
68. 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 19:1468-1473, 2005.
69. +/peptide transporter. J Nucl Med 49:615-622, 2008.
70. 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 brushborder membrane vesicles. Mol Membr Biol 22:549-559, 2005.
71. Murer H, Hopfer U, Kinne R. Sodium/proton antiport in brush-border-membrane vesicles isolated from rat small intestine and kidney. Biochem J 154:597-604, 1976.
72. Murray CM, Hutchinson R, Bantick JR, Belfield GP, Benjamin AD, Brazma D, Bundick RV, Cook ID, Craggs RI, Edwards S, Evans LR, Harrison R, Holness E, Jackson AP, Jackson CG, Kingston LP, Perry M W D, Ross A R J, Rugman PA, Sidhu SS, Sullivan M, Taylor-Fishwick DA, Walker PC, Whitehead YM, Wilkinson DJ, Wright A, Donald DK. Monocarboxylate transporter MCT1 is a target for immunosuppression. Nat Chem Biol 1:371-376, 2005.
73. Nabokina SM, Kashyap ML, Said HM. Mechanism and regulation of human intestinal niacin uptake. Am J Physiol Cell Physiol 289: C97-C103, 2005.
74. Nakanishi T, Tamai I, Takaki A, Tsuji A. Cancer cell-targeted drug delivery utilizing oligopeptide tansport activity. Int J Cancer 88:274-280, 2000.
75. 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 308:438-445, 2004.
76. Ocheltree SM, Shen H, Hu Y, Xiang J, Keep RF, Smith DE. Role of PEPT2 in the choroid plexus uptake of glycylsarcosine and 5-aminolevulinic acid: studies in wild-type and null mice. Pharm Res 21:1680-1685, 2004.
77. Ocheltree SM, Shen H, Hu Y, Keep RF, Smith DE. Role and relevance of peptide transporter 2 (PEPT2) in the kidney and choroid plexus: in vivo studies with glycylsarcosine in wild-type and PEPT2 knockout mice. J Pharmacol Exp Ther 315:240-247, 2005.
78. Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, Moriyama Y. A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci USA 102:17923-17928, 2005.
79. Palmieri F. The mitochondrial transporter family (SLC25): physiological and pathophysiological implications. Pflügers Arch 447:689-705, 2004.
80. Picollo A, Pusch M. Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. Nature 436:420-423, 2005.
81. Prasad PD, Mahesh VB, Leibach FH, Ganapathy V. Functional coupling between a bafilomycin A1-sensitive proton pump and a probenecid-sensitive folate transporter in human placental choriocarcinoma cells. Biochim Biophys Acta 1222:309-314, 1994.
82. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas H, Goldman ID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127:917-928, 2006.
83. Qiu A, Min SH, Jansen M, Malhotra U, Tsai E, Cabelof DC, Matherly LH, Zhao R, Akabas MY, Goldman ID. Rodent intestinal folate transporters (SLC46A1): secondary structure, functional properties, and response to dietary folate restriction. Am J Physiol Cell Physiol 293: C1669-C1678, 2007.
84. Rubio-Aliaga I, Daniel H. Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol Sci 23:434-440, 2002.
85. Rubio-Aliaga I, Frey I, Boll M, Groneberg DA, Eichinger HM, Balling R, Daniel H. Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney. Mol Cell Biol 23:3247-3252, 2003.
86. 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 98:7206-7211, 2001.
87. 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 34:1423-1431, 2006.
88. 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 33:518-523, 2005.
89. Scheel O, Zdebik AA, Lourdel S, Jentsch TJ. Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436:424-427, 2005.
90. + exchanger. Nat Genet 19:282-285, 1998.
91. Selhub J, Rosenberg IH. Folate transport in isolated brush border membrane vesicles from rat intestine. J Biol Chem 256:4489-4493, 1981.
92. 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. Identification of an intestinal heme transporter. Cell 122:789-801, 2005.
93. Shen H, Smith DE, Yang T, Huang YG, Schnermann JB, Brosius FC. Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney. Am J Physiol Renal Physiol 276: F658-F665, 1999.
94. + antiporter. Biochim Biophys Acta 937:328-334, 1988.
95. + gradient-driven dipeptide reabsorption in proximal tubule of rat kidney. Studies in vivo and in vitro. Am J Physiol Renal Fluid Electrolyte Physiol 253: F448-F457, 1987.
96. Smith ME, Matty AJ, Blair JA. The transport of pteroylglutamic acid across the small intestine of the rat. Biochim Biophys Acta 219:37-46, 1970.
97. Sun Y, Sun J, Shi S, Jing Y, Yin S, Chen Y, Li G, Xu Y, He Z. Synthesis, transport and pharmacokinetics of 5-amino acid ester prodrugs of 1-β-D-arabinofuranosylcytosine. Mol Pharm 6:315-325, 2009.
98. Tamai I, Nakanishi T, Kobayashi D, China K, Kosugi Y, Nezu J, Sai Y, Tsuji A. Involvement of OCTN1 (SLC22A4) in pH-dependent transport of organic cations. Mol Pharm 1:57-66, 2004.
99. Tamai I, Nakanishi T, Nakahara H, Sai Y, Ganapathy V, Leibach FH, Tsuji A. Improvement of l-Dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1. J Pharm Res 87:1542-1546, 1998.
100. 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 273:251-260, 2000.
101. 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 51:1113-1121, 1999.
102. Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, Tsuji A. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett 419:107-111, 1997.
103. +-organic cation antiporters. Biochem Pharmacol 74:359-371, 2007.
104. Tannock IF, Rotin D. Acid pH in tumors and its potential for therapeutic exploitation. Cancer Res 49:4373-4384, 1989.
105. +/organic cation antiporters (MATE/SLC47A). Biochem Pharmacol 75:1689-1696, 2008.
106. + fluxes through a channel. J Physiol 398:313-327, 1988.
107. Thwaites DT, Anderson C M H. Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1. Biochim Biophys Acta 1768:179-197, 2007.
108. +-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol 92:603-619, 2007.
109. +-coupled amino acid transporter. Br J Pharmacol 115:761-766, 1995.
110. Thwaites DT, Basterfield L, McCleave P M J, Carter SM, Simmons NL. Gamma-aminobutyric acid (GABA) transport across human intestinal epithelial (Caco-2) cell monolayers. Br J Pharmacol 129:629-635, 2000.
111. +-coupled carriers at both apical and basal membranes. J Biol Chem 268:7640-7642, 1993.
112. + exchanger. Gastroenterology 122:1322-1333, 2002.
113. +-coupled transepithelial beta-alanine absorption by human intestinal Caco-2 cell monolayers. J Biol Chem 268:18438-18441, 1993.
114. Thwaites DT, McEwan G T A, Brown C D A, Hirst BH, Simmons NL. L-Alanine absorption in human intestinal Caco-2 cells driven by the proton electrochemical gradient. J Membr Biol 140:143-151, 1994.
115. Thwaites DT, McEwan G T A, 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 145:245-256, 1995.
116. Tsuda M, Terada T, Mizuno T, Katsura T, Shimakura J, Inui K. Targeted disruption of the multidrug and toxin extrusion 1 (Mate1) gene in mice reduces renal secretion of metformin. Mol Pharmacol 75:1280-1286, 2009.
117. Tsume Y, Hilfinger JM, Amidon GL. Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm 5:717-727, 2008.
118. Umapathy NS, Gnana-Prakasam JP, Martin PM, Mysona B, Dun Y, Smith SB, Ganapathy V, Prasad PD. Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types. Invest Ophthalmol Vis Sci 48:5299-5305, 2007.
119. Urquhart BL, Kim RB. Blood-brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol 65:1063-1070, 2009.
120. Vanslambrouck JM, Bröer A, Thavyogarajah T, Holst J, Bailey CG, Bröer S, Rasko J E J. Renal imino acid and glycine transport system ontogeny and involvement in developmental iminoglycinuria. Biochem J 428:397-407, 2010.
121. Vieira FL, Malnic G. Hydrogen ion secretion by rat renal cortical tubules as studied by an antimony microelectrode. Am J Physiol 214:710-718, 1968.
122. + exchanger in primary cultures of astocytes from mouse cerebral cortex. Brain Res 1044:33-41, 2005.
123. Walker D, Thwaites DT, Simmons NL, Gilbert HJ, Hirst BH. Substrate up-regulation of the human small intestinal peptide transporter, hPepT1. J Physiol 507:697-706, 1998.
124. Wang L, Cherian C, Desmoulin SK, Polin L, Deng Y, Wu J, Hou Z, White K, Kushner J, Matherly LH, Ganglee A. Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2, 3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transport over the reduced folate carrier for cellular entry. J Med Chem 53:1306-1318, 2010.
125. Wang Y, Zhao R, Goldman ID. Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier. Clin Cancer Res 10:6256-6264, 2004.
126. Wike-Hooley JL, Haveman J, Reinhold HS. The relevance of tumour pH to the treatment of malignant disease. Radiother Oncol 2:343-366, 1984.
127. Wollack JB, Makori B, Ahlawat S, Koneru R, Picinich SC, Smith A, Goldman ID, Qiu A, Cole PD, Glod J, Kamen B. Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. J Neurochem 104:1494-1503, 2008.
128. Wright SH, Dantzler WH. Molecular and cellular physiology of renal organic cation and anion transport. Physiol Rev 84:987-1049, 2004.
129. Zhao R, Gao F, Hanscom M, Goldman ID. A prominent low-pH methotrexate transporter activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier. Clin Cancer Res 10:718-727, 2004.
130. Zhao R, Matherly LH, Goldman ID. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med 11: e4, 2009.
131. Zhao R, Min SH, Wang Y, Campanella E, Low PS, Goldman ID. A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate receptormediated endocytosis. J Biol Chem 284:4267-4274, 2009.
132. Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID. The proton-coupled folate transporter: impact on pemetrexed transport and on antifolate activities compared with the reduced folate carrier. Mol Pharmacol 74:854-862, 2008.
133. Zhou X, Thamotharan M, Gangopadhyay A, Serdikoff C, Adibi SA. Characterization of an oligopeptide transporter in renal lysosomes. Biochim Biophys Acta 1466:372-378, 2000.