Structure and function of eukaryotic peptide transporters

Cellular and Molecular Life Sciences

Volumn 57, Issue 5, 2000, Pages 754-778

  Meredith, D ^a   Boyd, C A R ^b  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Lactam antibiotics; Apical membrane; Basolateral membrane; Epithelia; Oligopeptide transport; PepT1; PepT2; PTR2

Indexed keywords

BETA LACTAM ANTIBIOTIC; OLIGOPEPTIDE; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATASE;

APICAL MEMBRANE; BASOLATERAL MEMBRANE; DRUG DESIGN; DRUG TARGETING; EPITHELIUM; NONHUMAN; PROTEIN STRUCTURE; PROTEIN TRANSPORT; REVIEW; TISSUE DISTRIBUTION;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; BIOLOGICAL TRANSPORT, ACTIVE; CAENORHABDITIS ELEGANS; CARRIER PROTEINS; FEMALE; GENOME; HORMONES; HUMANS; MOLECULAR SEQUENCE DATA; PEPTIDES; PREGNANCY; SECOND MESSENGER SYSTEMS; SEQUENCE HOMOLOGY, AMINO ACID; SYMPORTERS; TISSUE DISTRIBUTION;

CAENORHABDITIS ELEGANS; EUKARYOTA; MAMMALIA;

EID: 0034045632     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s000180050040     Document Type: Review

References (163)

1. 1 Nussberger S. and Hediger M. A. (1995) How peptides cross biological membranes. Exp. Nephrol. 3: 211-218
2. 2 Leibach F. H. and Ganapathy V. (1996) Peptide transporters in the intestine and the kidney. Annu. Rev. Nutr. 16: 99-119
3. 3 Ganapathy V. and Leibach F. H. (1996) Peptide transporters. Curr. Opin. Nephrol. Hypertens. 5: 395-400
4. + symporters. J. Membr. Biol. 154: 197-203
5. 5 Adibi S. A. (1997) Renal assimilation of oligopeptides: physiological mechanisms and metabolic importance. Am. J. Physiol. 272: E723-E736
6. 6 Adibi S. A. (1997) The oligopeptide transporter (Pept-1) in human intestine: biology and function. Gastroenterology 113: 332-340
7. 7 Daniel H. (1997) First insights into the operational mode of epithelial peptide transporters. J. Physiol. 498: 561
8. 8 Daniel H. and Herget M. (1997) Cellular and molecular mechanisms of renal peptide transport. Am. J. Physiol. 273: F1-F8
9. 9 Fei Y. J., Ganapathy V. and Leibach F. H. (1998) Molecular and structural features of the proton-coupled oligopeptide transporter superfamily. Prog. Nucleic Acid Res. Mol. Biol. 58: 239-261
10. 10 Yang C. Y., Dantzig A. H. and Pidgeon C. (1999) Intestinal peptide transport systems and oral drug availability. Pharm. Res. 16: 1331-1343
11. 11 Matthews D. M. (1991) Protein Absorption: Development and Present State of the Subject, Wiley-Liss, New York
12. 12 Meredith D. and Boyd C. A. R. (1995) Oligopeptide transport by epithelial cells. J. Memb. Biol. 145: 1-12
13. 13 Paulsen I. T. and Skurray R. A. (1994) The POT family of transport proteins. Trends Biochem. Sci. 19: 404
14. 14 Steiner H. Y., Naider F. and Becker J. M. (1995) The PTR family: a new group of peptide transporters. Mol. Microbiol. 16: 825-834
15. 15 Fei Y.-J., Fujita T., Lapp D. F, Ganapathy V. and Leibach F. H. (1998) Two oligopeptide transporters from Caenorhabditis elegans: molecular cloning and functional expression. Biochem J. 332: 565-572
16. 16 Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J. et al. (1994) 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature 368: 32-38
17. 17 Trombley P. Q. and Westbrook G. L. (1990) Excitatory synaptic transmission in cultures of rat olfactory bulb. J. Neurophysiol. 64: 598-606
18. 18 Wang H., Fei Y.-J., Ganapathy V. and Leibach F. H. (1998) Electrophysiological characteristics of the proton-coupled peptide transporter PEPT2 cloned from rat brain. Am. J. Physiol. 275: C967-C975
19. 19 Fei Y.-J., Kanai Y., Nussberger S., Ganapathy V., Leibach F. H., Romero M. F. et al. (1994) Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368: 563-566
20. 20 Nielsen H., Engelbrecht J., Brunak S. and von Heijne G. (1997) Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 10: 1-6
21. 21 Covitz K. M., Amidon G. L. and Sadee W. (1998) Membrane topology of the human dipeptide transporter, hPepT1, determined by epitope insertions. Biochemistry 37: 15214-15221
22. + /peptide cotransporter family, from human kidney. Biochim. Biophys. Acta 1235: 461-466
23. + di-tripeptide transporter (PepT1) expression in the rabbit intestine. Pflugers Arch. 430: 394-400
24. + peptide cotransporter in rat digestive tract. Biochem. Biophys. Res. Commun. 220: 848-852
25. 25 Ogihara H., Suzuki T., Nagamachi Y., Inui K. and Takata K. (1999) Peptide transporter in the rat small intestine: ultrastructural localization and the effect of starvation and administration of amino acids. Histochem. J. 31: 169-174
26. 26 Sai Y., Tamai I., Sumikawa H., Hayashi K., Nakanishi T., Amano O. et al. (1996) Immunolocalization and pharmacological relevance of oligopeptide transporter PepT1 in intestinal absorption of beta-lactam antibiotics. FEBS Lett. 392: 25-29
27. 27 Miyamoto K., Shiraga T., Morita K., Yamamoto H., Haga H., Taketani Y. et al. (1996) Sequence, tissue distribution and developmental changes in rat intestinal oligopeptide transporter. Biochim. Biophys. Acta 1305: 34-38
28. 28 Smith D. E., Pavlova A., Berger U. V., Hediger M. A., Yang T., Huang Y. G. et al. (1998) Tubular localization and tissue distribution of peptide transporters in rat kidney. Pharm. Res. 15: 1244-1249
29. 29 Shen H., Smith D. E., Yang T., Huang Y. G., Schnermann J. B. and Brosius F. C. (1999) Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney. Am. J. Physiol. 276: F658-F665
30. 30 Meredith D. and Boyd C. A. R. (1993) Peptide-transport in type-II pneumocytes freshly isolated from rat lung. J. Physiol. 467: P188
31. 31 Meredith D. and Boyd C. A. R. (1995) Dipeptide transport characteristics of the apical membrane of rat lung type II pneumocytes. Am. J. Physiol. 269: L137-L143
32. 32 Morimoto K., Yamahara H., Lee V. H. and Kim K. J. (1993) Dipeptide transport across rat alveolar epithelial cell monolayers. Pharm. Res. 10: 1668-1674
33. 33 Helliwell P. A., Meredith D., Boyd C. A. R., Bronk J. R., Lister N. and Bailey P. D. (1994) Tripeptide transport in rat lung. Biochim. Biophys. Acta 1190: 430-434
34. 34 Doring F., Walter J., Will J., Focking M., Boll M., Amasheh S. et al. (1998) Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J. Clin. Invest. 101: 2761-2767
35. 35 Morimoto K., Uehara Y., Iwanaga K. and Kakemi M. (1999) Tracheal barrier and the permeability of hydrophilic drugs and dipeptides. Biol. Pharm. Bull. 22: 510-514
36. 36 Ganapathy M. E., Mahesh V. B., Devoe L. D., Leibach F. H. and Ganapathy V. (1985) Dipeptide transport in brush-border membrane vesicles isolated from normal term human placenta. Am. J. Obstet. Gynecol. 153: 83-86
37. 37 Meredith D. and Laynes R. W. (1996) Dipeptide transport in brush-border membrane vesicles prepared from human full-term placentae. Placenta 17: 173-179
38. + /peptide cotransporter. Cloning, functional expression and chromosomal localization. J. Biol. Chem. 270: 6456-6463
39. 39 Adibi S. A., Schenker S. and Morse E. (1996) Mechanism of clearance and transfer of dipeptides by perfused human placenta. Am. J. Physiol. 271: E535-E540
40. 40 Reisenberger K., Egarter C., Sternberger B., Eckenberger P., Eberle E. and Weissenbacher E. R. (1996) Placental passage of angiotensin-converting enzyme inhibitors. Am. J. Obstet. Gynecol. 174: 1450-1455
41. 41 Shennan D. B., Calvert D. T., Backwell F. R. and Boyd C. A. R. (1998) Peptide aminonitrogen transport by the lactating rat mammary gland. Biochim. Biophys. Acta 1373: 252-260
42. 42 Bockman D. E., Ganapathy V., Oblak T. G. and Leibach F. H. (1997) Localization of peptide transporter in nuclei and lysosomes of the pancreas. Int. J. Pancreatol. 22: 221-225
43. 43 Thamotharan M., Lombardo Y. B., Bawani S. Z. and Adibi S. A. (1997) An active mechanism for completion of the final stage of protein degradation in the liver, lysosomal transport of dipeptides. J. Biol. Chem. 272: 11786-11790
44. 44 Nakanishi T., Tamai I., Sai Y., Sasaki T. and Tsuji A. (1997) Carrier-mediated transport of oligopeptides in the human fibrosarcoma cell line HT1080. Cancer Res. 57: 4118-4122
45. 45 Gonzalez D. E., Covitz K. M., Sadee W. and Mrsny, R.J.(1998) An oligopeptide transporter is expressed at high levels in the pancreatic carcinoma cell lines AsPc-1 and Capan-2. Cancer Res. 58: 519-525
46. 46 Fuhrman S., Palkovits M., Cassidy M. and Neale J. H. (1994) The regional distribution of N-acetylaspartylglutamate (NAAG) and peptidase activity against NAAG in the rat nervous system. J. Neurochem. 62: 275-281
47. 47 Westbrook G. L., Mayer M L., Namboodiri M. A. and Neale J. H. (1986) High concentrations of N-acetylaspartylglutamate (NAAG) selectively activate NMDA receptors on mouse spinal cord neurons in cell culture. J. Neurosci. 6: 3385-3392
48. 48 Wroblewska B., Santi M. R. and Neale J. H. (1998) N-acetylaspartylglutamate activates cyclic AMP-coupled metabotropic glutamate receptors in cerebellar astrocytes. Glia 24: 172-179
49. 49 Dieck S. T., Heuer H., Ehrchen J., Otto C. and Bauer K. (1999) The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative (beta)-Ala-Lys-N-(epsilon)-AMCA in astrocytes. Glia 25: 10-20
50. 50 Berger U. V. and Hediger M. A. (1999) Distribution of peptide transporter PFPT2 mRNA in the rat nervous system. Anat. Embryol. 199: 439-449
51. 51 Dringen R., Hamprecht B. and Broer S. (1998) The peptide transporter PepT2 mediates the uptake of the glutathione precursor CysGly in astroglia-rich primary cultures. J. Neurochem. 71: 388-393
52. + -dependent glutamate uptake. J. Neurosci. 18: 9620-9628
53. 53 Saunders N. R., Habgood M. D. and Dziegielewska K. M. (1999) Barrier mechanisms in the brain, I. Adult brain. Clin. Exp. Pharmacol. Physiol. 26: 11-19
54. 54 Torok M., Huwyler J., Drewe J., Gutmann H. and Fricker G. (1998) Transport of the β-lactam antibiotic benzylpenicillin and the dipeptide glycylsarcosine by brain capillary endothelial cells in vitro. Drug Metab. Dispos. 26: 1144-1148
55. 55 Miyamoto Y., Ganapathy V. and Leibach F. H. (1986) Identification of histidyl and thiol groups at the active site of rabbit renal dipeptide transporter. J. Biol. Chem. 261: 16133-16140
56. 56 Meredith D., Temple C. S. and Boyd C. A. R. (1996) Chemical evidence for the involvement of histidine residues in proton-peptide co-transport by PepT1 expressed in Xenopus laevis oocytes. J. Physiol. 493P: P65
57. 57 Meredith D. and Boyd C. A. R. (1996) His(57) is an essential residue for the transport of the anionic dipeptide D-Phe-L-Glu by PepT1 expressed in Xenopus laevis oocytes. J. Physiol. 497P: P89-P90
58. + /peptide cotransporter, PEPT1. FEBS Lett. 394: 196-200
59. + peptide cotransporters PEPT1 and PEPT2. Biochemistry 36: 452-460
60. 60 Yeung A. K., Basu S. K., Wu S. K., Chu C., Okamoto C. T., Hamm-Alvarez S. F. et al. (1998) Molecular identification of a role of tyrosine 167 in the function of the human intestinal proton-coupled dipeptide transporter (hPepT1). Biochem. Biophys. Res. Commun. 250: 103-107
61. 61 Bolger M. B., Haworth I. S., Yeung A. K., Ann D., von Grafenstein H., Hamm-Alvarez S. et al. (1998) Structure, function and molecular modelling approaches to the study of the intestinal dipeptide transporter PepT1. J. Pharm. Sci. 87: 1286-1291
62. 62 Doring F., Dorn D., Bachfischer U., Amasheh S., Herget M. and Daniel H. (1996) Functional analysis of a chimeric mammalian peptide transporter derived from the intestinal and renal isoforms. J. Physiol. 497: 773-779
63. 63 Fei Y. J., Liu J. C., Fujita T., Liang R., Ganapathy V. and Leibach F. H. (1998) Identification of a potential substrate binding domain in the mammalian peptide transporters PEPT1 and PEPT2 using PEPT1-PEPT2 and PEPT2-PEPT1 chimeras. Biochem. Biophys. Res. Commun. 246: 39-44
64. 64 Schultz, S. G., Field, M., Frizzell, R. A. and Rauner, B. B. (1991) The Gastrointestinal System, vol. 4, Intestinal Absorption and Secretion, American Physiological Society, Bethesda, MD
65. 65 Temple C. S., Stewart A. K., Meredith D., Lister N. A., Morgan K. M., Collier I. D. et al. (1998) Peptide mimics as substrates for the intestinal peptide transporter. J. Biol. Chem. 273: 20-22
66. 66 Meredith D., Boyd C. A. R., Bronk J. R., Bailey P. D., Morgan K. M., Collier I. D. et al. (1998) 4-Aminomethyl-benzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1. J. Physiol. 512: 629-634
67. 67 Abe H., Satoh M., Miyauchi S., Shuto S., Matsuda A. and Kamo N. (1999) Conjugation of dipeptide to fluorescent dyes enhances its affinity for a dipeptide transporter (PEPT1) in human intestinal Caco-2 cells. Bioconjug. Chem. 10: 24-31
68. 68 Doring F., Will J., Amasheh S., Clauss W., Ahlbrecht H. and Daniel H. (1998) Minimal molecular determinants of substrates for recognition by the intestinal peptide transporter. J. Biol. Chem. 273: 23211-23218
69. 69 Ganapathy M. E., Huang W., Wang H., Ganapathy V. and Leibach F. H. (1998) Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem. Biophys. Res. Commun. 246: 470-475
70. + /peptide cotransport system, PEPT1. Eur. J. Biochem. 255: 698-702
71. 71 Bailey P. D., Boyd C. A. R., Bronk J. R., Collier I. D., Meredith D., Morgan K. M. et al. (1999) How to make drugs orally active: a substrate model for the peplide transporter PepT1. Angew. Chem. Int. Ed. 39: 505-508
72. 72 Temple C. S., Bronk J. R., Bailey P. D. and Boyd C. A. R. (1995) Substrate-charge dependence of stoichiometry shows membrane potential is the driving force for proton-peptide cotransporl in rat renal cortex. Pflugers Arch. 430: 825-829
73. + -coupled oligopeptide transporter hPEPT1. J. Biol. Chem. 271: 5430-5437
74. 74 Steel A., Nussberger S., Romero M. F., Boron W. F., Boyd C. A. R. and Hediger M. A. (1997) Stoichiometry and pH dependence of the rabbit proton-dependent oligopeptide transporter PepT1. J. Physiol. 498: 563-569
75. + /peptide symporter PepT1 expressed in Xenopus laevis oocytes. J. Membr. Biol. 155: 247-256
76. + -coupled peptide transporter PepT2. J. Biol. Chem. 274: 2773-2779
77. 77 Amasheh S., Wenzel U., Weber W. M., Clauss W. and Daniel H. (1997) Electrophysiological analysis of the function of the mammalian renal peptide transporter expressed in Xenopus laevis oocytes. J. Physiol. 504: 169-174
78. 78 Fei Y. J., Nara E., Liu J. C., Boyd C. A. R., Ganapathy V. and Leibach F. H. (1999) Preferential recognition of zwitterionic dipeptides as transportable substrates by the high-affinity peptide transporter PEPT2. Biochim. Biophys. Acta 1418: 344-351
79. 79 Temple C. S., Bailey P. D., Bronk J. R. and Boyd C. A. R. (1996) A model for the kinetics of neutral and anionic dipeptide-proton cotransport by the apical membrane of rat kidney cortex. J. Physiol. 494: 795-808
80. + /oligopeptide cotransporter hPEPT1 transports differently-charged dipeptides with identical electrogenic properties. Biochim. Biophys. Acta 1284: 125-128
81. + co-transport system in the Caco-2 human colon carcinoma cell line. Biochem. J. 299: 253-260
82. + /peptide cotransporter in renal LLC-PK1 cells. J. Cell. Physiol. 178: 341-348
83. + exchangers NHE1 and NHE3 in Caco-2 cell monolayers. J. Physiol. 506P: 129
84. 84 Stewart A. K., Boyd C. A. R. and Vaughan-Jones R. D. (1999) A novel role for carbonic anhydrase: cytoplasmic pH gradient dissipation in mouse small intestinal enterocytes. J. Physiol. 516: 209-217
85. 85 Brandsch M., Ganapathy V. and Leibach F. H. (1995) H( + )-peptide cotransport in Madin-Darby canine kidney cells: expression and calmodulin-dependent regulation. Am. J. Physiol. 268: F391-397
86. + /peptide cotransporter in the human intestinal cell line Caco-2 by cyclic AMP. Biochem. Biophys. Res. Commun. 218: 461-465
87. + -dependent protein kinase A regulation of dipeptide uptake in Caco-2 cell monolayers. J. Physiol, in press (abstract)
88. + exchanger. J. Clin. Invest. 95: 2143-2149
89. + exchanger, NHE3, requires an associated regulatory protein. Proc. Natl. Acad. Sci. USA 94: 3010-3015
90. 90 Thamotharan M., Buwani S. Z., Xhou X. and Adibi S. A. (1999) Hormonal regulation of the oligopeptide transporter pept-1 in a human intestinal cell line. Am. J. Physiol. 276: C821-826
91. 91 Cheeseman C. I. (1997) Upregulation of SGLT-I transport activity in rat jejunum induced by GLP-2 infusion in vivo. Am. J. Physiol. 273: R1965-R1971
92. 92 Erickson R. H., Gum J. R., Lindstrom M. M., McKean D. and Kim Y. S. (1995) Regional expression and dietary regulation of rat small intestinal peptide and amino acid transporter mRNAs. Biochem. Biophys. Res. Commun. 216: 249-257
93. 93 Walker D., Thwaites D. T., Simmons N. L., Gilbert H. J. and Hirst B. H. (1998) Substrate upregulation of the human small intestinal peptide transporter, hPepT1. J. Physiol. 507: 697-706
94. 94 Thamotharan M., Bawani S. Z., Zhou X. and Adibi S. A. (1998) Mechanism of dipeptide stimulation of its own transport in human intestinal cell line. Proc. Assoc. Am. Physicians 110: 361-368
95. + /peptide transporter PepT1. Gastroenterology 116: 354-362
96. 96 Pohjanpelto P. and Holtta E. (1990) Deprivation of a single amino acid induces protein synthesis-dependent increases in c-jun, c-myc and ornithine decarboxylase mRNAs in Chinese hamster ovary cells. Mol. Cell Biol. 10: 5814-5821
97. 97 Guerrini L., Gong S. S., Mangasarian K. and Basilico C. (1993) Cis- and trans-acting elements involved in amino acid regulation of asparagine synthetase gene expression. Mol. Cell Biol. 13: 3202-3212
98. 98 Ford D., Geggie M. A. and Hirst B. H. (1999) Proton specificity for up-regulation of the human proton-coupled peptide transporter, hPepT1, in human intestinal Caco-2 cells. J. Physiol., in press (abstract)
99. 99 Thamotharan M., Bawani S. Z., Zhou X. and Adibi S. A. (1999) Functional and molecular expression of intestinal oligopeptide transporter (Pept-1) after a brief fast. Metabolism 48: 681-684
100. 100 Tanaka H., Miyamoto K. I., Morita K., Haga H., Segawa H., Shiraga T. et al. (1998) Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil induced injury. Gastroenterology 114: 714-723
101. + peptide transporter PEPT1 in the human intestinal cell line caco-2. Biochem. Biophys. Res. Commun. 261: 242-246
102. 102 Kekuda R., Prasad P. D., Fei Y. J., Leibach F. H. and Ganapathy V. (1996) Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1). Biochem. Biophys. Res. Commun. 229: 553-558
103. 103 Harcouet L., Lebrec D., Roze C., Carbon C. and Farinotti R. (1997) Increased intestinal absorption of cefixime by nifedipine in the rat intestinal perfusion model: evidence for a neural regulation. J. Pharmacol. Exp. Ther. 281: 738-745
104. 104 Man H. K., Rhie J. K., Oh D. M., Saito G., Hsu C. P., Stewart B. H. et al. (1999) CHO hPEPT1 cells overexpressing the human peptide transporter (hPEPT1 ) as an alternative in vitro model for peptidomimetic drugs. J. Pharm. Sci. 88: 347-350
105. 105 Tamai I., Nakanishi T., Hayashi K., Terao T., Sai Y., Shiraga T. et al. (1997) The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J. Pharm. Pharmacol. 49: 796-801
106. 106 Covitz K. M., Amidon G. L. and Sadee W. (1996) Human dipeptide transporter, hPEPT1, stably transfected into Chinese hamster ovary cells. Pharm. Res. 13: 1631-1634
107. 107 Wenzel U., Thwaites D. T. and Daniel H. (1995) Stereoselective uptake of beta-lactam antibiotics by the intestinal peptide transporter. Br. J. Pharmacol. 116: 3021-3027
108. 108 Matsumoto S., Saito H. and Inui K. (1994) Transcellular transport of oral cephalosporins in human intestinal epithelial cells, Caco-2: interaction with dipeptide transport systems in apical and basolateral membranes. J. Pharmacol. Exp. Ther. 270: 498-504
109. 109 Wolffram S., Grenacher B. and Scharrer E. (1998) H( + )-coupled uphill transport of the dipeptide glycylsarcosine by bovine intestinal brush-border membrane vesicles. J. Dairy Sci. 81: 2595-2603
110. 110 Tamura K., Lee C. P., Smith P. L. and Borchardt R. T. (1996) Metabolism, uptake, and transepithelial transport of the stereoisomers of Val-Val-Val in the human intestinal cell line, Caco-2. Pharm. Res. 13: 1663-1667
111. 111 Daniel H and Adibi S. A. (1995) Selective effect of zinc on uphill transport of oligopeptides into kidney brush border membrane vesicles. FASEB J. 9: 1112-1117
112. + peptide cotransporters in rat renal brush-border membranes. J. Pharmacol. Exp. Ther. 286: 1037-1042
113. 113 Swaan P. W., Stehouwer M. C. and Tukker J. J. (1995) Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors: enalapril, enalaprilat, and lisinopril. Biochim. Biophys. Acta 1236: 31-38
114. 114 Ganapathy M. E., Brandsch M., Prasad P. D., Ganapathy V. and Leibach F. H. (1995) Differential recognition of beta-lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. J. Biol. Chem. 270: 25672-25677
115. 115 Poschet J. F., Hammond S. M. and Fairclough P. D. (1999) Characterisation of penicillin G uptake in human small intestinal brush border membrane vesicles. Gut 44: 620-624
116. 116 Terada T., Saito H., Mukai M. and Inui K. (1997) Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am. J. Physiol. 273: F706 F711
117. + /peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J. Pharmacol. Exp. Ther. 275: 1631-1637
118. 118 Ganapathy M. E., Prasad P. D., Mackenzie B., Ganapathy V. and Leibach F. H. (1997) Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim. Biophys. Acta 1324: 296-308
119. + /peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J. Pharmacol. Exp. Ther. 281: 1415-1421
120. + -dependent transport mechanism of dipeptide and anionic beta-lactam antibiotic ceftibuten in rat intestinal brush-border membrane. J. Pharmacol. Exp. Ther. 289: 66-71
121. 121 Naasani I., Kikuchi T., Sugawara M., Kobayashi M., Iseki K. and Miyazaki K. (1996) Solubilization and reconstitution characteristics of the carrier protein(s) responsible for the transport of ceftibuten, a substrate for the oligopeptide transporters, in rat renal brush-border membrane. Biochim. Biophys. Acta 1283: 185-191
122. + dipeptide cotransport system in human intestinal cell line Caco-2: regulation by cell growth. Pharm. Res. 12: 1483-1487
123. 123 Naasani I., Sato K., Iseki K., Sugawara M., Kobayashi M. and Miyazaki K. (1995) Comparison of the transport characteristics of ceftibuten in rat renal and intestinal brush-border membranes. Biochim. Biophys. Acta 1231: 163-168
124. 124 Naasani I., Sugawara M., Kobayashi M., Iseki K. and Miyazaki K. (1995) Transport mechanism of ceftibuten, a dianionic cephem, in rat renal brush-border membrane. Pharm. Res. 12: 605-608
125. 125 Muranushi N., Horie K., Masuda K. and Hirano K. (1994) Characteristics of ceftibuten uptake into Caco-2 cells. Pharm. Res. 11: 1761-1765
126. 126 Dantzig A. H., Duckworth D. C. and Tabas L. B. (1994) Transport mechanisms responsible for the absorption of loracarbef, cefixime and cefuroxime axetil into human intestinal Caco-2 cells. Biochim. Biophys. Acta 1191: 7-13
127. 127 Wenzel U., Gebert I., Weintraut H., Weber W. M., Clauss W. and Daniel H. (1996) Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells. J. Pharmacol. Exp. Ther. 277: 831-839
128. 128 Boll M., Markovich D., Weber W. M., Korte H., Daniel H. and Murer H. (1994) Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, beta-lactam antibiotics and ACE-inhibitors. Pflugers Arch. 429: 146-149
129. 129 Boll M., Herget M., Wagener M., Weber W. M., Markovich D., Biber J. et al. (1996) Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc. Natl. Acad. Sci. USA 93: 284-289
130. 130 Boll M. and Daniel H. (1995) Target size analysis of the peptide, H( + )-symporter in kidney brush-border membranes. Biochim. Biophys. Acta 1233: 145-152
131. 131 Doring F., Theis S. and Daniel H. (1997) Expression and functional characterization of the mammalian intestinal peptide transporter PepT1 in the methylotropic yeast Pichia pastoris. Biochem. Biophys. Res. Commun. 232: 656-662
132. 132 Kitagawa S., Sugaya Y., Kaseda Y. and Sato S. (1997) Characteristics of cefdinir uptake by rabbit small intestinal brush-border membrane vesicles. J. Pharm. Pharmacol. 49: 516-519
133. 133 Kitagawa S., Takeda J., Kaseda Y. and Sato S. (1997) Inhibitory effects of angiotensin-converting enzyme inhibitor on cefroxadine uptake by rabbit small intestinal brush border membrane vesicles. Biol. Pharm. Bull. 20: 449-451
134. + /dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells. J. Pharmacol. Exp. Ther. 272: 63-69
135. 135 Basu S. K., Haworth I. S., Bolger M. B. and Lee V. H. (1998) Proton-driven dipeptide uptake in primary cultured rabbit conjunctival epithelial cells. Invest. Ophthalmol. Vis. Sci. 39: 2365-2373
136. 136 Muranushi N., Hashimoto N. and Hirano K. (1995) Transport characteristics of S-1090, a new oral cephem, in ratintestinal brush-border membrane vesicles. Pharm. Res. 12: 1488-1492
137. 137 Temple C. S. and Boyd C. A. R. (1998) Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter. Biochim. Biophys. Acta 1373: 277-281
138. + /peptide symporter. Pharm. Res. 16: 609-615
139. 139 Schoenmakers R. G., Stehouwer M. C. and Tukker J. J. (1999) Structure-transport relationship for the intestinal small-peptide carrier: is the carbonyl group of the peptide bond relevant for transport? Pharm. Res. 16: 62-68
140. 140 Morrison R. A., Chong S., Marino A. M., Wasserman M. A., Timmins P., Moore V. A. et al. (1996) Suitability of enalapril as a probe of the dipeptide transporter system: in vitro and in vivo studies. Pharm. Res. 13: 1078-1082
141. 141 Akarawut W., Lin C. J. and Smith D. E. (1998) Noncompetitive inhibition of glycylsarcosine transport by quinapril in rabbit renal brush border membrane vesicles: effect on high-affinity peptide transporter. J. Pharmacol. Exp. Ther. 287: 684-690
142. 142 Hashimoto N., Fujioka T., Toyoda T., Muranushi N. and Hirano K. (1994) Renin inhibitor: transport mechanism in rat small intestinal brush-border membrane vesicles. Pharm. Res. 11: 1448-1451
143. + /peptide cotransporters, PEPT1 and PEPT2. J. Biol. Chem. 273: 5582-5585
144. 144 Schwerdt G., Gekle M., Freudinger R., Mildenberger S. and Silbernagl S. (1997) Apical-to-basolateral transepithelial transport of Ochratoxin A by two subtypes of Madin-Darby canine kidney cells. Biochim. Biophys. Acta 1324: 191-199
145. 145 Merlin D., Steel A., Gewirtz A. T., Si-Tahar M., Hediger M. A. and Madara J. L. (1998) hPepT1-mediated epithelial transport of bacteria-derived chemotactic peptides enhances neutrophil-epithelial interactions. J. Clin. Invest. 102: 2011-2018
146. 146 Soul-Lawton J., Seaber E., On N., Wootton R., Rolan P. and Posner J. (1995) Absolute bioavailability and metabolic disposition of valacyclovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrob. Agents Chemother. 39: 2759-2764
147. 147 Balimane P. V., Tamai I., Guo A., Nakanishi T., Kitada H., Leibach F. H. et al. (1998) Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir. Biochem. Biophys. Res. Commun. 250: 246-251
148. 148 Han H., de Vrueh R.L., Rhie J. K., Covitz K. M., Smith P. L., Lee C. P. et al. (1998) 5′-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm. Res. 15: 1154-1159
149. 149 Guo A., Peidi H. U., Balimane P. V., Leibach F. H. and Sinko P. J. (1999) Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPepT1) expressed in a mammalian cell line. J. Pharm. Exp. Ther. 289: 448-454
150. 150 Tamai I., Nakanishi T., Nakahara H., Sai Y., Ganapathy V., Leibach F. H. et al. (1999) Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1. J. Pharm. Sci. 87: 1542-1546
151. 151 Weiss W. J., Mikels S. M., Petersen P. J., Jacobus N. V., Bitha P., Lin Y. I. et al. (1999) In vivo activities of peptidic prodrugs of novel aminomethyl tetrahydrofuranyl-1 β-methylcarbapenems. Antimicrob. Agents Chemother. 43: 460-464
152. 152 Hu M., Chen J., Zhu Y., Dantzig A. H., Stratford R. E. and Kuhfeld M. T. (1994) Mechanism and kinetics of transcellular transport of a new beta-lactam antibiotic loracarbef across an intestinal epithelial membrane model system (Caco-2). Pharm. Res. 11:1405-1413
153. 153 Thwaites D. T., Brown C. D. A., Hisrt B. H. and Simmons N. L. (1993) 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
154. 154 Thamotharan M., Zonno V., Storelli C. and Ahearn G. A. (1996) Basolateral dipeptide transport by the intestine of the teleost Oreochromis mossambicus. Am. J. Physiol. 270: R948 R954
155. 155 TeradaT., Sawada K., Saito H., Hashimoto Y. and Inui K. I. (1999) Functional characteristics of basolateral peptide transporter in the human intestinal cell line Caco-2. Am. J. Physiol. 276: G1435-G1441
156. 156 Thwaites D. T., Torras-Llort M. and Christie G. R. (1999) Dipeptide uptake across the basolateral membrane of human intestinal epithelial Caco-2 cell monolayers. J. Physiol., in press (abstract)
157. 157 Lister N., Sykes A. P., Bailey P. D., Boyd C. A. R. and Bronk J. R. (1995) Dipeptide transport and hydrolysis in isolated loops of rat small intestine: effects of stereospecificity. J. Physiol. 484: 173-182
158. 158 Dantzig A. H., Hoskins J. A., Tabas L. B., Bright S., Shepard R. L., Jenkins I. L. et al. (1994) Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science 264: 430-433
159. 159 Yamashita T., Shimada S., Guo W., Sato K., Kohmura E., Hayakawa T. et al. (1997) Cloning and functional expression of a brain peptide/histidine transporter. J. Biol. Chem. 272: 10205-10211
160. + /peptide cotransporter, PEPT1. Biochem. Biophys. Res. Commun. 237: 577-582
161. 161 Sleigh S. H., Seavers P. R., Wilkinson A. J., Ladbury J. E. and Tame J. R. (1999) Crystallographic and calorimetric analysis of peptide binding to OppA protein. J. Mol. Biol. 291: 393-415
162. 162 Davies T. G., Hubbard R. E. and Tame J. R. (1999) Relating structure to thermodynamics: the crystal structures and binding affinity of eight OppA-peptide complexes. Protein Sci. 8: 1432-1444
163. 163 Andersen M. H., Bonfill J. E., Neisig A., Arsequell G., Sondergaard I., Neefjes J. et al. (1999) Phosphorylated peptides can be transported by TAP molecules, presented by class I MHC molecules, and recognized by phosphopeptide-specific CTL. J. Immunol. 163: 3812-3818