SEARCH

SEARCH BY CITATION

References

  • Abderhalden, E. (1911) Die Bedeutung der Verdauung für den Zellstoffwechsel im Lichte neuer Forschungen auf dem Gebiete der physiologischen Chemie. Urban & Schwarzenberg, Berlin-Wien.
  • Abe, H., Satoh, M., Miyauchi, S., Shuto, S., Matsuda, A., 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: 2431.
  • Addison, J. M., Burston, D., Matthews, D. M. (1972) Evidence for active transport of the dipeptide glycylsarcosine by hamster jejunum in vitro. Clin. Sci. 43: 907911.
  • Addison, J. M., Burston, D., Dalrymple, J. A., Matthews, D. M., Payne, J. W., Sleisenger, M. H., Wilkinson, S. (1975) A common mechanism for transport of di- and tri-peptides by hamster jejunum in vitro. Clin. Sci. Mol. Med. 49: 313322.
  • Adibi, S. A. (1997) The oligopeptide transporter (Pept-1) in human intestine: biology and function. Gastroenterology 113: 332340.
  • Adibi, S. A. (2003) Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease. Am. J. Physiol. 285: G779G788.
  • Adibi, S. A., Soleimanpour, M. R. (1974) Functional characterization of dipeptide transport system in human jejunum. J. Clin. Invest. 53: 13681374.
  • Akarawut, W., Lin, C. J., 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: 684690.
  • Amasheh, S., Wenzel, U., Boll, M., Dorn, D., Weber, W., Clauss, W., Daniel, H. (1997) Transport of charged dipeptides by the intestinal H+/peptide symporter PepT1 expressed in Xenopus laevis oocytes. J. Membr. Biol. 155: 247256.
  • Amidon, G. L., Sadée, W., (eds) (1999) Membrane transporters as drug targets. Pharmaceutical biotechnology volume 12. Kluwer Academic/Plenum Publishers. New York.
  • Anderle, P., Nielsen, C. U., Pinsonneault, J., Krog, P. L., Brodin, B., Sadee, W. (2006) Genetic variants of the human dipeptide transporter PEPT1. J. Pharmacol. Exp. Ther. 316: 636646.
  • Andersen, R., Jorgensen, F. S., Olsen, L., Vabeno, J., Thorn, K., Nielsen, C. U., Steffansen, B. (2006) Development of a QSAR model for binding of tripeptides and tripeptidomimetics to the human intestinal di-/tripeptide transporter hPEPT1. Pharm. Res. 23: 483492.
  • Aronson, P. S., Nee, J., Suhm, M. A. (1982) Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles. Nature 299: 161163.
  • Asatoor, A. M., Cheng, B., Edwards, K. D., Lant, A. F., Matthews, D. M., Milne, M. D., Navab, F., Richards, A. J. (1970) Intestinal absorption of two dipeptides in Hartnup disease. Gut 11: 380387.
  • Bai, J. P., Amidon, G. L. (1992) Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery. Pharm. Res. 9: 969978.
  • Bailey, P. D. (2005) Thiopeptide conjugates for drug delivery. Patent WO/2005/067978.
  • Bailey, P. D., Boyd, C. A., Collier, I. D., Kellett, G. L., Meredith, D., Morgan, K. M., Pettecrew, R., Price, R. A. (2005) Probing dipeptide trans/cis stereochemistry using pH control of thiopeptide analogues, and application to the PepT1 transporter. Org. Biomol. Chem. 3: 40384039.
  • Bailey, P. D., Boyd, C. A., Collier, I. D., George, J. P., Kellett, G. L., Meredith, D., Morgan, K. M., Pettecrew, R., Price, R. A. (2006) Affinity prediction for substrates of the peptide transporter PepT1. Chem. Commun. (Camb.) 2006: 323325.
  • Balimane, P. V., Tamai, I., Guo, A., Nakanishi, T., Kitada, H., Leibach, F. H., Tsuji, A., Sinko, P. J. (1998) Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir. Biochem. Biophys. Res. Commun. 250: 246251.
  • Banks, W. A. (2006) The CNS as a target for peptides and peptide-based drugs. Expert Opin. Drug Deliv. 3: 707712.
  • Banks, W. A., Kastin, A. J. (1996) Passage of peptides across the blood-brain barrier: pathophysiological perspectives. Life Sci. 59: 19231943.
  • Beattie, L. A., Boyd, C. A. R. (2001) Protein kinase C activation directly alters the kinetics of PepT1-mediated peptide transport. J. Physiol. 535P.
  • Beauchamp, L. M., Orr, G. F., De Miranda, P., Burnette, T., Krenitsky, T. A. (1992) Amino acid ester prodrugs of acyclovir. Antiv. Chem. Chemother. 3: 157164.
  • Becker, J. M., Dunsmore, K. P., Steinfeld, A. S., Naider, F. (1982) Photoinactivation of peptide transport in Saccharomyces cerevisiae. Biochemistry 21: 59675971.
  • Begley, D. J. (1996) The blood-brain barrier: principles for targeting peptides and drugs to the central nervous system. J. Pharm. Pharmacol. 48: 136146.
  • Berger, U. V., Hediger, M. A. (1999) Distribution of peptide transporter PEPT2 mRNA in the rat nervous system. Anat. Embryol. (Berl.) 199: 439449.
  • Bertrams, A., Ziegler, K. (1991) Hepatocellular uptake of peptides by bile acid transporters: relationship of carrier-mediated transport of linear peptides with renin-inhibiting activity to multispecific bile acid carriers. Biochim. Biophys. Acta. 1091: 337348.
  • Beyenbach, K. W., Wieczorek, H. (2006) The V-type H+ ATPase: molecular structure and function, physiological roles and regulation. J. Exp. Biol. 209: 577589.
  • Bhardwaj, R. K., Herrera-Ruiz, D., Sinko, P. J., Gudmundsson, O. S., Knipp, G. (2005) Delineation of human peptide transporter 1 (hPepT1)-mediated uptake and transport of substrates with varying transporter affinities utilizing stably transfected hPepT1/Madin-Darby Canine Kidney clones and Caco-2 cells. J. Pharmacol. Exp. Ther. 314: 10931100.
  • Bhardwaj, R. K., Herrera-Ruiz, D., Eltoukhy, N., Saad, M., Knipp, G. T. (2006) The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells. Eur. J. Pharm. Sci. 27: 533542.
  • Bickel, U., Yoshikawa, T., Pardridge, W. M. (2001) Delivery of peptides and proteins through the blood-brain barrier. Adv. Drug Deliv. Rev. 46: 247279.
  • Biegel, A., Gebauer, S., Hartrodt, B., Brandsch, M., Neubert, K., Thondorf, I. (2005) Three-dimensional quantitative structure-activity relationship analyses of β-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J. Med. Chem. 48: 44104419.
  • Biegel, A., Gebauer, S., Brandsch, M., Neubert, K., Thondorf, I. (2006a) Structural requirements for the substrates of the H+/peptide cotransporter PEPT2 determined by three-dimensional quantitative structure-activity relationship analysis. J. Med. Chem. 49: 42864296.
  • Biegel, A., Knütter, I., Hartrodt, B., Gebauer, S., Theis, S., Luckner, P., Kottra, G., Rastetter, M., Zebisch, K., Thondorf, I., Daniel, H., Neubert, K., Brandsch, M. (2006b) The renal type H+/peptide symporter PEPT2: structure-affinity relationships. Amino Acids 31: 137156.
  • Bockman, D. E., Ganapathy, V., Oblak, T. G., Leibach, F. H. (1997) Localization of peptide transporter in nuclei and lysosomes of the pancreas. Int. J. Pancreatol. 22: 221225.
  • Bolger, M. B., Haworth, I. S., Yeung, A. K., Ann, D., Von Grafenstein, H., Hamm-Alvarez, S., Okamoto, C. T., Kim, K. J., Basu, S. K., Wu, S., Lee, V. H. (1998) Structure, function, and molecular modeling approaches to the study of the intestinal dipeptide transporter PepT1. J. Pharm. Sci. 87: 12861291.
  • Boll, M., Markovich, D., Weber, W. M., Korte, H., Daniel, H., Murer, H. (1994) Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, ß-lactam antibiotics and ACE-inhibitors. Pflügers Arch. 429: 146149.
  • Boll, M., Herget, M., Wagener, M., Weber, W. M., Markovich, D., Biber, J., Clauss, W., Murer, H., Daniel, H. (1996) Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc. Natl Acad. Sci. USA 93: 284289.
  • Börner, V., Fei, Y. J., Hartrodt, B., Ganapathy, V., Leibach, F. H., Neubert, K., Brandsch, M. (1998) Transport of amino acid aryl amides by the intestinal H+/peptide cotransport system, PEPT1. Eur. J. Biochem. 255: 698702.
  • Brandsch, M. (2006) Transport of L-proline, L-proline-containing peptides and related drugs at mammalian epithelial cell membranes. Amino Acids 31: 119136.
  • Brandsch, M., Miyamoto, Y., Ganapathy, V., Leibach, F. H. (1994) Expression and protein kinase C-dependent regulation of peptide/H+ cotransport system in the Caco-2 human colon carcinoma cell line. Biochem. J. 299: 253260.
  • Brandsch, M., Brandsch, C., Prasad, P. D., Ganapathy, V., Hopfer, U., Leibach, F. H. (1995) Identification of a renal cell line that constitutively expresses the kidney-specific high-affinity H+/peptide cotransporter. FASEB J. 9: 14891496.
  • Brandsch, M., Brandsch, C., Ganapathy, M. E., Chew, C. S., Ganapathy, V., Leibach, F. H. (1997) Influence of proton and essential histidyl residues on the transport kinetics of the H+/peptide cotransport systems in intestine (PEPT 1) and kidney (PEPT 2). Biochim. Biophys. Acta. 1324: 251262.
  • Brandsch, M., Thunecke, F., Küllertz, G., Schutkowski, M., Fischer, G., Neubert, K. (1998) Evidence for the absolute conformational specificity of the intestinal H+/peptide symporter, PEPT1. J. Biol. Chem. 273: 38613864.
  • Brandsch, M., Knütter, I., Thunecke, F., Hartrodt, B., Born, I., Börner, V., Hirche, F., Fischer, G., Neubert, K. (1999) Decisive structural determinants for the interaction of proline derivatives with the intestinal H+/peptide symporter. Eur. J. Biochem. 266: 502508.
  • Brandsch, M., Knütter, I., Leibach, F. H. (2004) The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur. J. Pharm. Sci. 21: 5360.
  • Bravo, S. A., Nielsen, C. U., Frokjaer, S., Brodin, B. (2005) Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media. Mol. Pharm. 2: 98108.
  • Bretschneider, B., Brandsch, M., Neubert, R. (1999) Intestinal transport of ß-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm. Res. 16: 5561.
  • Brodin, B., Nielsen, C. U., Steffansen, B., Frokjaer, S. (2002) Transport of peptidomimetic drugs by the intestinal di/tri-peptide transporter, PepT1. Pharmacol. Toxicol. 90: 285296.
  • Bröer, A., Cavanaugh, J. A., Rasko, J. E., Bröer, S. (2006) The molecular basis of neutral aminoacidurias. Pflügers Arch. 451: 511517.
  • Bueno, A. B., Collado, I., De Dios, A., Dominguez, C., Martin, J. A., Martin, L. M., Martinez-Grau, M. A., Montero, C., Pedregal, C., Catlow, J., Coffey, D. S., Clay, M. P., Dantzig, A. H., Lindstrom, T., Monn, J. A., Jiang, H., Schoepp, D. D., Stratford, R. E., Tabas, L. B., Tizzano, J. P., Wright, R. A., Herin, M. F. (2005) Dipeptides as effective prodrugs of the unnatural amino acid (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), a selective group II metabotropic glutamate receptor agonist. J. Med. Chem. 48: 53055320.
  • Charrier, L., Driss, A., Yan, Y., Nduati, V., Klapproth, J. M., Sitaraman, S. V., Merlin, D. (2006) hPepT1 mediates bacterial tripeptide fMLP uptake in human monocytes. Lab. Invest. 86: 490503.
  • Chen, X. Z., Zhu, T., Smith, D. E., Hediger, M. A. (1999) Stoichiometry and kinetics of the high-affinity H+-coupled peptide transporter PepT2. J. Biol. Chem. 274: 27732779.
  • Chen, X. Z., Steel, A., Hediger, M. A. (2000) Functional roles of histidine and tyrosine residues in the H+-peptide transporter PepT1. Biochem. Biophys. Res. Commun. 272: 726730.
  • Cheon, E. P., Hong, J. H., Han, H. K. (2006) Enhanced cellular uptake of Ara-C via a peptidomimetic prodrug, L-valyl-ara-C in Caco-2 cells. J. Pharm. Pharmacol. 58: 927932.
  • Chu, X. Y., Bleasby, K., Yabut, J., Cai, X., Chan, G. H., Hafey, M. J., Xu, S., Bergman, A. J., Braun, M. P., Dean, D. C., Evers, R. (2007) Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J. Pharmacol. Exp. Ther. 321: 673683.
  • Cohnheim, O. (1901) Die Umwandlung des Eiweiss durch die Darmwand. Z. Physiol. Chemie 33: 451465.
  • Covitz, K. M., Amidon, G. L., Sadee, W. (1998) Membrane topology of the human dipeptide transporter, hPEPT1, determined by epitope insertions. Biochemistry 37: 1521415221.
  • Dalton, J. T., Meyer, M. C., Golub, A. L. (1999) Pharmacokinetics of aminolevulinic acid after oral and intravenous administration in dogs. Drug Metab. Dispos. 27: 432435.
  • Daniel, H. (2004) Molecular and integrative physiology of intestinal peptide transport. Annu. Rev. Physiol. 66: 361384.
  • Daniel, H., Adibi, S. A. (1993) Transport of ß-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter. J. Clin. Invest. 92: 22152223.
  • Daniel, H., Adibi, S. A. (1994) Functional separation of dipeptide transport and hydrolysis in kidney brush border membrane vesicles. FASEB J. 8: 753759.
  • Daniel, H., Kottra, G. (2004) The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflügers Arch. 447: 610618.
  • Daniel, H., Rubio-Aliaga, I. (2003) An update on renal peptide transporters. Am. J. Physiol. 284: F885F892.
  • Daniel, H., Fett, C., Kratz, A. (1989) Demonstration and modification of intervillous pH profiles in rat small intestine in vitro. Am. J. Physiol. 257: G489G495.
  • Daniel, H., Morse, E. L., Adibi, S. A. (1991) The high and low affinity transport systems for dipeptides in kidney brush border membrane respond differently to alterations in pH gradient and membrane potential. J. Biol. Chem. 266: 1991719924.
  • Daniel, H., Morse, E. L., Adibi, S. A. (1992) Determinants of substrate affinity for the oligopeptide/H+ symporter in the renal brush border membrane. J. Biol. Chem. 267: 95659573.
  • Dantzig, A. H., Duckworth, D. C., Tabas, L. B. (1994a) Transport mechanisms responsible for the absorption of loracarbef, cefixime, and cefuroxime axetil into human intestinal Caco-2 cells. Biochim. Biophys. Acta. 1191: 713.
  • Dantzig, A. H., Hoskins, J. A., Tabas, L. B., Bright, S., Shepard, R. L., Jenkins, I. L., Duckworth, D. C., Sportsman, J. R., Mackensen, D., Rosteck, P. R., Jr. (1994b) Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science 264: 430433.
  • Dieck, S. T., Heuer, H., Ehrchen, J., Otto, C., Bauer, K. (1999) The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative β-Ala-Lys-N-epsilon-AMCA in astrocytes. Glia 25: 1020.
  • Döring, F., Dorn, D., Bachfischer, U., Amasheh, S., Herget, M., Daniel, H. (1996) Functional analysis of a chimeric mammalian peptide transporter derived from the intestinal and renal isoforms. J. Physiol. 497: 773779.
  • Döring, F., Walter, J., Will, J., Focking, M., Boll, M., Amasheh, S., Clauss, W., Daniel, H. (1998a) δ-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J. Clin. Invest. 101: 27612767.
  • Döring, F., Will, J., Amasheh, S., Clauss, W., Ahlbrecht, H., Daniel, H. (1998b) Minimal molecular determinants of substrates for recognition by the intestinal peptide transporter. J. Biol. Chem. 273: 2321123218.
  • Döring, F., Martini, C., Walter, J., Daniel, H. (2002) Importance of a small N-terminal region in mammalian peptide transporters for substrate affinity and function. J. Membr. Biol. 186: 5562.
  • Dyer, J., Beechey, R. B., Gorvel, J. P., Smith, R. T., Wootton, R., Shirazi-Beechey, S. P. (1990) Glycyl-L-proline transport in rabbit enterocyte basolateral-membrane vesicles. Biochem. J. 269: 565571.
  • Eckhardt, U., Horz, J. A., Petzinger, E., Stuber, W., Reers, M., Dickneite, G., Daniel, H., Wagener, M., Hagenbuch, B., Stieger, B., Meier, P. J. (1996) The peptide-based thrombin inhibitor CRC 220 is a new substrate of the basolateral rat liver organic anion-transporting polypeptide. Hepatology 24: 380384.
  • Eddy, E. P., Wood, C., Miller, J., Wilson, G., Hidalgo, I. J. (1995) A comparison of the affinities of dipeptides and antibiotics for the di-/tripeptide transporter in Caco-2 cells. Int. J. Pharm. 115: 7986.
  • Ekins, S., Johnston, J. S., Bahadduri, P., D'souza, V. M., Ray, A., Chang, C., Swaan, P. W. (2005) In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors. Pharm. Res. 22: 512517.
  • Enjoh, M., Hashimoto, K., Arai, S., Shimizu, M. (1996) Inhibitory effect of arphamenine A on intestinal dipeptide transport. Biosci. Biotechnol. Biochem. 60: 18931895.
  • Ermisch, A., Brust, P., Kretzschmar, R., Rühle, H.-J. (1993) Peptides and blood-brain barrier transport. Physiol. Rev. 73: 489527.
  • Faria, T. N., Timoszyk, J. K., Stouch, T. R., Vig, B. S., Landowski, C. P., Amidon, G. L., Weaver, C. D., Wall, D. A., Smith, R. L. (2004) A novel high-throughput PepT1 transporter assay differentiates between substrates and antagonists. Mol. Pharm. 1: 6776.
  • Fei, Y. J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F. H., Romero, M. F., Singh, S. K., Boron, W. F., Hediger, M. A. (1994) Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368: 563566.
  • Fei, Y. J., Liu, W., Prasad, P. D., Kekuda, R., Oblak, T. G., Ganapathy, V., Leibach, F. H. (1997) Identification of the histidyl residue obligatory for the catalytic activity of the human H+/peptide cotransporters PEPT1 and PEPT2. Biochemistry 36: 452460.
  • Fei, Y. J., Ganapathy, V., Leibach, F. H. (1998a) Molecular and structural features of the proton-coupled oligopeptide transporter superfamily. Prog. Nucleic Acid Res. Mol. Biol. 58: 239261.
  • Fei, Y. J., Liu, J. C., Fujita, T., Liang, R., Ganapathy, V., Leibach, F. H. (1998b) 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: 3944.
  • Fei, Y. J., Nara, E., Liu, J. C., Boyd, C. A., Ganapathy, V., Leibach, F. H. (1999) Preferential recognition of zwitterionic dipeptides as transportable substrates by the high-affinity peptide transporter PEPT2. Biochim. Biophys. Acta. 1418: 344351.
  • Foltz, M., Meyer, A., Theis, S., Demuth, H. U., Daniel, H. (2004) A rapid in vitro screening for delivery of peptide-derived peptidase inhibitors as potential drug candidates via epithelial peptide transporters. J. Pharmacol. Exp. Ther. 310: 695702.
  • Freeman, T. C., Bentsen, B. S., Thwaites, D. T., Simmons, N. L. (1995) H+/di-tripeptide transporter (PepT1) expression in the rabbit intestine. Pflügers Arch. 430: 394400.
  • Frey, I. M., Rubio-Aliaga, I., Klempt, M., Wolf, E., Daniel, H. (2006) Phenotype analysis of mice deficient in the peptide transporter PEPT2 in response to alterations in dietary protein intake. Pflügers Arch. 452: 300306.
  • Frey, I. M., Rubio-Aliaga, I., Siewert, A., Sailer, D., Drobyshev, A., Beckers, J., De Angelis, M. H., Aubert, J., Bar, H. A., Fiehn, O., Eichinger, H. M., Daniel, H. (2007) Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue of Pept2−/– mice. Physiol. Genomics 28: 301310.
  • Fürst, P., Albers, S., Stehle, P. (1990) Dipeptides in clinical nutrition. Proc. Nutr. Soc. (UK) 49: 343359.
  • Fujita, T., Kishida, T., Okada, N., Ganapathy, V., Leibach, F. H., Yamamoto, A. (1999) Interaction of kyotorphin and brain peptide transporter in synaptosomes prepared from rat cerebellum: implication of high affinity type H+/peptide transporter PEPT2 mediated transport system. Neurosci. Lett. 271: 117120.
  • Fujita, T., Kishida, T., Wada, M., Okada, N., Yamamoto, A., Leibach, F. H., Ganapathy, V. (2004) Functional characterization of brain peptide transporter in rat cerebral cortex: identification of the high-affinity type H+/peptide transporter PEPT2. Brain Res. 997: 5261.
  • Fujiya, M., Musch M. W., Nakagawa, Y., Hu, S., Alverdy, J., Kohgo, Y., Schneewind, O., Jabri, B., Chang, E. B. (2007) The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe 1: 299308.
  • Ganapathy, V., Leibach, F. H. (1983) Role of pH gradient and membrane potential in dipeptide transport in intestinal and renal brush-border membrane vesicles from the rabbit. Studies with L-carnosine and glycyl-L-proline. J. Biol. Chem. 258: 1418914192.
  • Ganapathy, V., Miyauchi, S. (2005) Transport systems for opioid peptides in mammalian tissues. AAPS. J. 7: E852E856.
  • Ganapathy, V., Radhakrishnan, A. N. (1979) Interaction of amino acids with glycl-L-leucine hydrolysis and transport in monkey small intestine. Clin. Sci. (Lond.) 57: 521527.
  • Ganapathy, V., Mendicino, J., Pashley, D. H., Leibach, F. H. (1980) Carrier-mediated transport of glycyl-L-proline in renal brush border vesicles. Biochem. Biophys. Res. Commun. 97: 11331139.
  • Ganapathy, V., Mendicino, J. F., Leibach, F. H. (1981) Transport of glycyl-L-proline into intestinal and renal brush border vesicles from rabbit. J. Biol. Chem. 256: 118124.
  • Ganapathy, V., Burckhardt, G., Leibach, F. H. (1984) Characteristics of glycylsarcosine transport in rabbit intestinal brush-border membrane vesicles. J. Biol. Chem. 259: 8954895.
  • Ganapathy, V., Brandsch, M., Leibach, F. H. (1994) Intestinal transport of amino acids and peptides. In: Johnson, L. R. (ed.) Physiology of the gastrointestinal tract. 3rd edn, Raven Press Ltd, New York, pp 17731794.
  • Ganapathy, M. E., Brandsch, M., Prasad, P. D., Ganapathy, V., Leibach, F. H. (1995) Differential recognition of ß-lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. J. Biol. Chem. 270: 2567225677.
  • Ganapathy, M. E., Prasad, P. D., Mackenzie, B., Ganapathy, V., Leibach, F. H. (1997) Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim. Biophys. Acta. 1324: 296308.
  • Ganapathy, M. E., Huang, W., Wang, H., Ganapathy, V., Leibach, F. H. (1998) Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem. Biophys. Res. Commun. 246: 470475.
  • Ganapathy, M. E., Huang, W., Rajan, D. P., Carter, A. L., Sugawara, M., Iseki, K., Leibach, F. H., Ganapathy, V. (2000) β-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J. Biol. Chem. 275: 16991707.
  • Ganapathy, V., Ganapathy, M. E., Leibach, F. H. (2001) Intestinal transport of peptides and amino acids. In: Barrett, K. E., Donowitz, M. (ed.) Gastrointestinal transport. Molecular physiology. Vol. 50, Academic Press, San Diego, pp 379412.
  • Gao, B., Hagenbuch, B., Kullak-Ublick, G. A., Benke, D., Aguzzi, A., Meier, P. J. (2000) Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier. J. Pharmacol. Exp. Ther. 294: 7379.
  • Gebauer, S., Knütter, I., Hartrodt, B., Brandsch, M., Neubert, K., Thondorf, I. (2003) Three-dimensional quantitative structure-activity relationship analyses of peptide substrates of the mammalian H+/peptide cotransporter PEPT1. J. Med. Chem. 46: 57255734.
  • Genz, A. K., Von Engelhardt, W., Busche, R. (1999) Maintenance and regulation of the pH microclimate at the luminal surface of the distal colon of guinea-pig. J. Physiol. 517: 507519.
  • Gerloff, T. (2004) Impact of genetic polymorphisms in transmembrane carrier-systems on drug and xenobiotic distribution. Naunyn Schmiedebergs Arch. Pharmacol. 369: 6977.
  • Goodman, S. I., McIntyre, C. A., O'Brien, D. (1967) Impaired intestinal transport of proline in a patient with familial iminoaciduria. J. Pediatr. 71: 246249.
  • Gray, V. A., Dressman, J. B. (1996) Change of pH requirements for simulated intestinal fluid TS. Pharmacopeial Forum 22: 19431945.
  • Groneberg, D. A., Nickolaus, M., Springer, J., Döring, F., Daniel, H., Fischer, A. (2001) Localization of the peptide transporter PEPT2 in the lung: implications for pulmonary oligopeptide uptake. Am. J. Pathol. 158: 707714.
  • Groneberg, D. A., Döring, F., Theis, S., Nickolaus, M., Fischer, A., Daniel, H. (2002) Peptide transport in the mammary gland: expression and distribution of PEPT2 mRNA and protein. Am. J. Physiol. 282: E1172E1179.
  • Groneberg, D. A., Fischer, A., Chung, K. F., Daniel, H. (2004) Molecular mechanisms of pulmonary peptidomimetic drug and peptide transport. Am. J. Respir. Cell Mol. Biol. 30: 251260.
  • Groneberg, D. A., Paul, H., Welte, T. (2006) Novel strategies of aerosolic pharmacotherapy. Exp. Toxicol. Pathol. 57: 4953.
  • Hagenbuch, B., Meier, P. J. (2004) Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflügers Arch. 447: 653665.
  • Han, H., De Vrueh, R. L., Rhie, J. K., Covitz, K. M., Smith, P. L., Lee, C. P., Oh, D. M., Sadee, W., Amidon, G. L. (1998) 5′-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm. Res. 15: 11541159.
  • Han, H. K., Rhie, J. K., Oh, D. M., Saito, G., Hsu, C. P., Stewart, B. H., Amidon, G. L. (1999) CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J. Pharm. Sci. 88: 347350.
  • Hartrodt, B., Börner, V., Knütter, I., Born, I., Brandsch, M., Neubert, K. (1998) Intestinal H+/peptide cotransport: Investigation of transporter-substrate interaction. In: Bajusz, S., Hudecz, F. (eds) Peptides 1998. Akademiai Kiado, Budapest, pp 586587.
  • Hartrodt, B., Theis, S., Knütter, I., Börner, V., Born, I., Brandsch, M., Daniel, H., Neubert, K. (2001) New insight into the stereospecificity of the intestinal H+/peptide symporter. In: Martinez, J., Fehrentz, J.-A. (eds) Peptides 2000. Editions EDK, Paris, pp 983984.
  • Hediger, M. A. (special editor) (2004) The ABC of solute transporters. Pflügers Arch. 447: 5.
  • Hellier, M. D., Holdsworth, C. D., Perrett, D., Thirumalai, C. (1972) Intestinal dipeptide transport in normal and cystinuric subjects. Clin. Sci. 43: 659668.
  • Hellier, M. D., Radhakrishnan, A. N., Ganapathy, V., Mathan, V. I., Baker, S. J. (1976) Intestinal perfusion studies in tropical sprue. 1. Amino acid and dipeptide absorption. Gut 17: 511516.
  • Herget, M., Tampe, R. (2007) Intracellular peptide transporters in human-compartmentalization of the peptidome. Pflügers Arch. 453: 591600.
  • Herrera-Ruiz, D., Knipp, G. T. (2003) Current perspectives on established and putative mammalian oligopeptide transporters. J. Pharm. Sci. 92: 691714.
  • Hori, R., Tomita, Y., Katsura, T., Yasuhara, M., Inui, K., Takano, M. (1993) Transport of bestatin in rat renal brush-border membrane vesicles. Biochem. Pharmacol. 45: 17631768.
  • Hu, M., Subramanian, P., Mosberg, H. I., Amidon, G. L. (1989) Use of the peptide carrier system to improve the intestinal absorption of L-alpha-methyldopa: carrier kinetics, intestinal permeabilities, and in vitro hydrolysis of dipeptidyl derivatives of L-α-methyldopa. Pharm. Res. 6: 6670.
  • Hu, M., Zheng, L., Chen, J., Liu, L., Zhu, Y., Dantzig, A. H., Stratford, R. E. (1995) Mechanisms of transport of quinapril in Caco-2 cell monolayers: comparison with cephalexin. Pharm. Res. 12: 11201125.
  • Hu, H., Miyauchi, S., Bridges, C. C., Smith, S. B., Ganapathy, V. (2003) Identification of a novel Na+- and Cl-coupled transport system for endogenous opioid peptides in retinal pigment epithelium and induction of the transport system by HIV-1 Tat. Biochem. J. 375: 1722.
  • Hu, Y., Shen, H., Keep, R. F., Smith, D. E. (2007) Peptide transporter 2 (PEPT2) expression in brain protects against 5-aminolevulinic acid neurotoxicity. J. Neurochem. 103: 20582065.
  • Hussain, I., Zanic-Grubisic, T., Kudo, Y., Boyd, C. A. (2001) Functional and molecular characterization of a peptide transporter in the rat PC12 neuroendocrine cell line. FEBS Lett. 508: 350354.
  • Inui, K., Terada, T. (1999) Dipeptide transporters. Pharm. Biotechnol. 12: 269288.
  • 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: 195201.
  • Irie, M., Terada, T., Sawada, K., Saito, H., Inui, K. (2001) Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells. J. Pharmacol. Exp. Ther. 298: 711717.
  • Irie, M., Terada, T., Okuda, M., Inui, K. (2004) Efflux properties of basolateral peptide transporter in human intestinal cell line Caco-2. Pflügers Arch. 449: 186194.
  • Iseki, K., Sugawara, M., Saitoh, H., Miyazaki, K., Arita, T. (1989) Comparison of transport characteristics of amino ß-lactam antibiotics and dipeptides across rat intestinal brush border membrane. J. Pharm. Pharmacol. 41: 628632.
  • Ismair, M. G., Stieger, B., Cattori, V., Hagenbuch, B., Fried, M., Meier, P. J., Kullak-Ublick, G. A. (2001) Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides oatp4 and oatp8 of rat and human liver. Gastroenterology 121: 11851190.
  • Kastin, A. J., Pan, W. (2003) Peptide transport across the blood-brain barrier. Prog. Drug Res. 61: 79100.
  • Kitagawa, S., Takeda, J., Kaseda, Y., 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: 449451.
  • Klapper, M., Daniel, H., Döring, F. (2006) Cytosolic COOH terminus of the peptide transporter PEPT2 is involved in apical membrane localization of the protein. Am. J. Physiol. 290: C472C483.
  • Knütter, I., Theis, S., Hartrodt, B., Born, I., Brandsch, M., Daniel, H., Neubert, K. (2001) A novel inhibitor of the mammalian peptide transporter PEPT1. Biochemistry 40: 44544458.
  • Knütter, I., Rubio-Aliaga, I., Boll, M., Hause, G., Daniel, H., Neubert, K., Brandsch, M. (2002) H+-peptide cotransport in the human bile duct epithelium cell line SK-ChA-1. Am. J. Physiol. 283: G222G229.
  • Knütter, I., Hartrodt, B., Theis, S., Foltz, M., Rastetter, M., Daniel, H., Neubert, K., Brandsch, M. (2004) Analysis of the transport properties of side chain modified dipeptides at the mammalian peptide transporter PEPT1. Eur. J. Pharm. Sci. 21: 6167.
  • König, J., Seithel, A., Gradhand, U., Fromm, M. F. (2006) Pharmacogenomics of human OATP transporters. Naunyn Schmiedebergs Arch. Pharmacol. 372: 432443.
  • Kottra, G., Stamfort, A., Daniel, H. (2002) PEPT1 as a paradigm for membrane carriers that mediate electrogenic bidirectional transport of anionic, cationic, and neutral substrates. J. Biol. Chem. 277: 3268332691.
  • Kulkarni, A. A., Haworth, I. S., Lee, V. H. (2003a) Transmembrane segment 5 of the dipeptide transporter hPepT1 forms a part of the substrate translocation pathway. Biochem. Biophys. Res. Commun. 306: 177185.
  • Kulkarni, A. A., Haworth, I. S., Uchiyama, T., Lee, V. H. (2003b) Analysis of transmembrane segment 7 of the dipeptide transporter hPepT1 by cysteine-scanning mutagenesis. J. Biol. Chem. 278: 5183351840.
  • Kulkarni, A. A., Davies, D. L., Links, J. S., Patel, L. N., Lee, V. H., Haworth, I. S. (2007) A charge pair interaction between Arg282 in transmembrane segment 7 and Asp341 in transmembrane segment 8 of hPepT1. Pharm. Res. 24: 6672.
  • Landowski, C. P., Vig, B. S., Song, X., Amidon, G. L. (2005) Targeted delivery to PEPT1-overexpressing cells: acidic, basic, and secondary floxuridine amino acid ester prodrugs. Mol. Cancer Ther. 4: 659667.
  • Lankat-Buttgereit, B., Tampe, R. (2002) The transporter associated with antigen processing: function and implications in human diseases. Physiol. Rev. 82: 187204.
  • Law, E. A., Sardharwalla, I. B. (1978) A new type of heterozygote of familial renal iminoglycinuria. Monogr. Hum. Genet. 9: 152154.
  • Leabman, M. K., Huang, C. C., DeYoung, J., Carlson, E. J., Taylor, T. R., De La, C. M., Johns, S. J., Stryke, D., Kawamoto, M., Urban, T. J., Kroetz, D. L., Ferrin, T. E., Clark, A. G., Risch, N., Herskowitz, I., Giacomini, K. M. Pharmacogenetics of membrane transporters investigators 2003. Natural variation in human membrane transporter genes reveals evolutionary and functional constraints. Proc. Natl Acad. Sci. USA 100: 58965901.
  • Lee, C. P., De Vrueh, R. L., Smith, P. L. (1996) Transport of a prod-rug of acyclovir, L-valacyclovir, via the oligopeptide transporter. Proc. Int. Symp. Controlled Release Bioact. Mater. 23: 4748.
  • Lee, V. H., Chu, C., Mahlin, E. D., Basu, S. K., Ann, D. K., Bolger, M. B., Haworth, I. S., Yeung, A. K., Wu, S. K., Hamm-Alvarez, S., Okamoto, C. T. (1999) Biopharmaceutics of transmucosal peptide and protein drug administration: role of transport mechanisms with a focus on the involvement of PepT1. J. Control. Release 62: 129140.
  • Leibach, F. H., Ganapathy, V. (1996) Peptide transporters in the intestine and the kidney. Annu. Rev. Nutr. 16: 99119.
  • Li, J., Tamura, K., Lee, C. P., Smith, P. L., Borchardt, R. T., Hidalgo, I. J. (1998) Structure-affinity relationships of Val-Val and Val-Val-Val stereoisomers with the apical oligopeptide transporter in human intestinal Caco-2 cells. J. Drug Target. 5: 317327.
  • Li, F., Hong, L., Mau, C. I., Chan, R., Hendricks, T., Dvorak, C., Yee, C., Harris, J., Alfredson, T. (2006a) Transport of levovirin prodrugs in the human intestinal Caco-2 cell line. J. Pharm. Sci. 95: 13181325.
  • Li, M., Anderson, G. D., Phillips, B. R., Kong, W., Shen, D. D., Wang, J. (2006b) Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab. Dispos. 34: 547555.
  • Liang, R., Fei, Y. J., Prasad, P. D., Ramamoorthy, S., Han, H., Yang-Feng, T. L., Hediger, M. A., Ganapathy, V., Leibach, F. H. (1995) Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization. J. Biol. Chem. 270: 64566463.
  • Lin, H., King, N. (2007) Demonstration of functional dipeptide transport with expression of PEPT2 in guinea pig cardiomyocytes. Pflügers Arch. 453: 915922.
  • Lin, C. J., Akarawut, W., Smith, D. E. (1999) Competitive inhibition of glycylsarcosine transport by enalapril in rabbit renal brush border membrane vesicles: interaction of ACE inhibitors with high-affinity H+/peptide symporter. Pharm. Res. 16: 609615.
  • Links, J. L., Kulkarni, A. A., Davies, D. L., Lee, V. H., Haworth, I. S. (2007) Cysteine scanning of transmembrane domain three of the human dipeptide transporter: implications for substrate transport. J. Drug Target. 15: 218225.
  • Liu, W., Liang, R., Ramamoorthy, S., Fei, Y. J., Ganapathy, M. E., Hediger, M. A., Ganapathy, V., Leibach, F. H. (1995) Molecular cloning of PEPT 2, a new member of the H+/peptide cotrans-porter family, from human kidney. Biochim. Biophys. Acta. 1235: 461466.
  • Liu, K. X., Kato, Y., Kaku, T. I., Santa, T., Imai, K., Yagi, A., Ishizu, T., Sugiyama, Y. (2000) Hydroxyprolylserine derivatives JBP923 and JBP485 exhibit the antihepatitis activities after gastrointestinal absorption in rats. J. Pharmacol. Exp. Ther. 294: 510515.
  • Lucas, M. (1983) Determination of acid surface pH in vivo in rat proximal jejunum. Gut 24: 734739.
  • Luckner, P., Brandsch, M. (2005) Interaction of 31 ß-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur. J. Pharm. Biopharm. 59: 1724.
  • Matsumoto, S., Saito, H., 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: 498504.
  • Matthews, D. M. (1975) Intestinal absorption of peptides. Physiol. Rev. 55: 537608.
  • Matthews, D. M. (1991) Protein absorption: development and present state of the subject. Wiley-Liss, New York.
  • Matthews, D. M., Addison, J. M., Burston, D. (1974) Evidence for active transport of the dipeptide carnosine (β-alanyl-l-histidine) by hamster jejunum in vitro. Clin. Sci. Mol. Med. 46: 693705.
  • McEwan, G. T., Daniel, H., Fett, C., Burgess, M. N., Lucas, M. L. (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: 219237.
  • Meissner, B., Boll, M., Daniel, H., Baumeister, R. (2004) Deletion of the intestinal peptide transporter affects insulin and TOR signaling in Caenorhabditis elegans. J. Biol. Chem. 279: 3673936745.
  • Meredith, D. (2004) Site-directed mutation of arginine 282 to glutamate uncouples the movement of peptides and protons by the rabbit proton-peptide cotransporter PepT1. J. Biol. Chem. 279: 1579515798.
  • Meredith, D., Boyd, C. A. (1995) Dipeptide transport characteristics of the apical membrane of rat lung type II pneumocytes. Am. J. Physiol. 269: L137L143.
  • Meredith, D., Boyd, C. A. (2000) Structure and function of eukaryotic peptide transporters. Cell. Mol. Life Sci. 57: 754778.
  • Meredith, D., Boyd, C. A., Bronk, J. R., Bailey, P. D., Morgan, K. M., Collier, I. D., Temple, C. S. (1998) 4-Aminomethylbenzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1. J. Physiol. 512: 629634.
  • Meredith, D., Temple, C. S., Guha, N., Sword, C. J., Boyd, C. A., Collier, I. D., Morgan, K. M., Bailey, P. D. (2000) Modified amino acids and peptides as substrates for the intestinal peptide transporter PepT1. Eur. J. Biochem. 267: 37233728.
  • Miyauchi, S., Gopal, E., Thakkar, S. V., Ichikawa, S., Prasad, P. D., Ganapathy, V. (2007) Differential modulation of sodium- and chloride-dependent opioid peptide transport system by small non-opioid peptides and free amino acids. J. Pharmacol. Exp. Ther. 321: 257264.
  • Moore, V. A., Irwin, W. J., Timmins, P., Lambert, P. A., Chong, S., Dando, S. A., Morrison, R. A. (2000) A rapid screening system to determine drug affinities for the intestinal dipeptide transporter 2: affinities of ACE inhibitors. Int. J. Pharm. 210: 2944.
  • Nakashima, E., Tsuji, A., Mizuo, H., Yamana, T. (1984) Kinetics and mechanism of in vitro uptake of amino-ß-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system. Biochem. Pharmacol. 33: 33453352.
  • Neumann, J., Brandsch, M. (2003) δ-aminolevulinic acid transport in cancer cells of the human extrahepatic biliary duct. J. Pharmacol. Exp. Ther. 305: 219224.
  • Neumann, J., Bruch, M., Gebauer, S., Brandsch, M. (2004) Transport of the phosphonodipeptide alafosfalin by the H+/peptide cotransporters PEPT1 and PEPT2 in intestinal and renal epithelial cells. Eur. J. Biochem. 271: 20122017.
  • Newey, H., Smyth, D. H. (1959) The intestinal absorption of some dipeptides. J. Physiol. 145: 4856.
  • Nicklin, P. L., Irwin, W. J., Timmins, P., Morrison, R. A. (1996) Uptake and transport of the ACE-inhibitor ceronapril (SQ 29852) by monolayers of human intestinal absorptive (Caco-2) cells in vitro. Int. J. Pharm. 140: 175183.
  • Nielsen, C. U., Andersen, R., Brodin, B., Frokjaer, S., Taub, M. E., Steffansen, B. (2001) Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepT1 in the human intestinal Caco-2 cell line. J. Control. Release 76: 129138.
  • Nielsen, C. U., Brodin, B., Jorgensen, F. S., Frokjaer, S., Steffansen, B. (2002a) Human peptide transporters: therapeutic applications. Expert Opin. Ther. Patents 12: 13291350.
  • Nielsen, C. U., Supuran, C. T., Scozzafava, A., Frokjaer, S., Steffansen, B., Brodin, B. (2002b) Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonyl-ureido-carnosine in a human epithelial cell line. Pharm. Res. 19: 13371344.
  • Nielsen, C. U., Brodin, B. (2003) Di/tri-peptide transporters as drug delivery targets: regulation of transport under physiological and patho-physiological conditions. Curr. Drug Targets 4: 373388.
  • Novotny, A., Xiang, J., Stummer, W., Teuscher, N. S., Smith, D. E., Keep, R. F. (2000) Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus. J. Neurochem. 75: 321328.
  • Nozawa, T., Toyobuku, H., Kobayashi, D., Kuruma, K., Tsuji, A., Tamai, I. (2003) Enhanced intestinal absorption of drugs by activation of peptide transporter PEPT1 using proton-releasing polymer. J. Pharm. Sci. 92: 22082216.
  • Ocheltree, S. M., Shen, H., Hu, Y., Xiang, J., Keep, R. F., Smith, D. E. (2004a) Role of PEPT2 in the choroid plexus uptake of glycyl-sarcosine and 5-aminolevulinic acid: studies in wild-type and null mice. Pharm. Res. 21: 16801685.
  • Ocheltree, S. M., Shen, H., Hu, Y., Xiang, J., Keep, R. F., Smith, D. E. (2004b) Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and PEPT2 knockout mice. J. Pharmacol. Exp. Ther. 308: 462467.
  • Ocheltree, S. M., Shen, H., Hu, Y., Keep, R. F., Smith, D. E. (2005) 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: 240247.
  • Ogihara, H., Saito, H., Shin, B. C., Terado, T., Takenoshita, S., Nagamachi, Y., Inui, K., Takata, K. (1996) Immuno-localization of H+/peptide cotransporter in rat digestive tract. Biochem. Biophys. Res. Commun. 220: 848852.
  • Okano, T., Inui, K., Maegawa, H., Takano, M., Hori, R. (1986) H+ coupled uphill transport of aminocephalosporins via the dipeptide transport system in rabbit intestinal brush-border membranes. J. Biol. Chem. 261: 1413014134.
  • Palacin, M., Nunes, V., Font-Llitjos, M., Jimenez-Vidal, M., Fort, J., Gasol, E., Pineda, M., Feliubadalo, L., Chillaron, J., Zorzano, A. (2005) The genetics of heteromeric amino acid transporters. Physiology 20: 11224.
  • Pan, W., Kastin, A. J. (2004) Polypeptide delivery across the blood-brain barrier. Curr. Drug Targets CNS Neurol. Disord. 3: 131136.
  • Pardridge, W. M. (1992) Recent developments in peptide drug delivery to the brain. Pharmacol. Toxicol. 71: 310.
  • Pardridge, W. M., Frank, H. J., Cornford, E. M., Braun, L. D., Crane, P. D., Oldendorf, W. H. (1981) Neuropeptides and the blood-brain barrier. Adv. Biochem. Psychopharmacol. 28: 321328.
  • Paulsen, I. T., Skurray, R. A. (1994) The POT family of transport proteins. Trends Biochem. Sci. 19: 404.
  • Payne, J. W., Payne, G. M., Gupta, S., Marshall, N. J., Grail, B. M. (2001) Conformational limitations of glycylsarcosine as a proto-typic substrate for peptide transporters. Biochim. Biophys. Acta. 1514: 6575.
  • Petzinger, E., Wickboldt, A., Pagels, P., Starke, D., Kramer, W. (1999) Hepatobiliary transport of bile acid amino acid, bile acid peptide, and bile acid oligonucleotide conjugates in rats. Hepatology 30: 12571268.
  • Pinsonneault, J., Nielsen, C. U., Sadee, W. (2004) Genetic variants of the human H+/dipeptide transporter PEPT2: analysis of haplo-type functions. J. Pharmacol. Exp. Ther. 311: 10881096.
  • Prasad, P. D., Mahesh, V. B., Leibach, F. H., Ganapathy, V. (1994) Functional coupling between a bafilomycin A1-sensitive proton pump and a probenecid-sensitive folate transporter in human placental choriocarcinoma cells. Biochim. Biophys. Acta. 1222: 309314.
  • Quay, J. F. (1972) Transport interaction of glycine and cephalexin in rat jejunum. The Physiologist 15: 241.
  • Quay, J. F., Foster, L. (1970) Cephalexin penetration of the surviving rat intestine. The Physiologist 13: 287.
  • Raeissi, S. D., Li, J., Hidalgo, I. J. (1999) The role of an alpha-amino group on H+-dependent transepithelial transport of cephalosporins in Caco-2 cells. J. Pharm. Pharmacol. 51: 3540.
  • Rochat, B., Audus, K. L. (1999) Drug disposition and targeting. Transport across the blood-brain barrier. Pharm. Biotechnol. 12: 181200.
  • Rubio-Aliaga, I., Daniel, H. (2002) Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol. Sci. 23: 434440.
  • Rubio-Aliaga, I., Frey, I., Boll, M., Groneberg, D. A., Eichinger, H. M., Balling, R., Daniel, H. (2003) Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney. Mol. Cell Biol. 23: 32473252.
  • Rühl, A., Hoppe, S., Frey, I., Daniel, H., Schemann, M. (2005) Functional expression of the peptide transporter PEPT2 in the mammalian enteric nervous system. J. Comp. Neurol. 490: 111.
  • Sai, Y., Tsuji, A. (2004) Transporter-mediated drug delivery: recent progress and experimental approaches. Drug Discov. Today 9: 712720.
  • Said, H. M., Blair, J. A., Lucas, M. L., Hilburn, M. E. (1986) Intestinal surface acid microclimate in vitro and in vivo in the rat. J. Lab. Clin. Med. 107: 420424.
  • Saito, H., Inui, K. (1993) Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2. Am. J. Physiol. 265: G289G294.
  • Saito, H., Terada, T., Okuda, M., Sasaki, S., Inui, K. (1996) Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim. Biophys. Acta. 1280: 173177.
  • Saito, H., Motohashi, H., Mukai, M., Inui, K. (1997) Cloning and characterization of a pH-sensing regulatory factor that modulates transport activity of the human H+/peptide cotransporter, PEPT1. Biochem. Biophys. Res. Commun. 237: 577582.
  • Saitoh, H., Gerard, C., Aungst, B. J. (1996) The secretory intestinal transport of some ß-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption. J. Pharmacol. Exp. Ther. 278: 205211.
  • Sakata, K., Yamashita, T., Maeda, M., Moriyama, Y., Shimada, S., Tohyama, M. (2001) Cloning of a lymphatic peptide/histidine transporter. Biochem. J. 356: 5360.
  • Sala-Rabanal, M., Loo, D. D., Hirayama, B. A., Turk, E., Wright, E. M. (2006) Molecular interactions between dipeptides, drugs and the human intestinal H+-oligopeptide cotransporter hPEPT1. J. Physiol. 574: 149166.
  • Sawada, K., Terada, T., Saito, H., Hashimoto, Y., Inui, K. (1999a) Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2. Br. J. Pharmacol. 128: 11591164.
  • Sawada, K., Terada, T., Saito, H., Hashimoto, Y., Inui, K. I. (1999b) Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2. J. Pharmacol. Exp. Ther. 291: 705709.
  • Seal, C. J., Parker, D. S. (1991) Isolation and characterization of circulating low molecular weight peptides in steer, sheep and rat portal and peripheral blood. Comp. Biochem. Physiol. B 99: 679685.
  • Seow, H. F., Bröer, S., Bröer, A., Bailey, C. G., Potter, S. J., Cavanaugh, J. A., Rasko, J. E. (2004) Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat. Genet. 36: 10031007.
  • Shen, H., Smith, D. E., Yang, T., Huang, Y. G., Schnermann, J. B., Brosius, F. C. 3rd (1999) Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney. Am. J. Physiol. 276: F658F665.
  • Shen, H., Smith, D. E., Keep, R. F., Xiang, J., Brosius, F. C. 3rd (2003) Targeted disruption of the PEPT2 gene markedly reduces dipeptide uptake in choroid plexus. J. Biol. Chem. 278: 47864791.
  • Shen, H., Ocheltree, S. M., Hu, Y., Keep, R. F., Smith, D. E. (2007) Impact of genetic knockout of PEPT2 on cefadroxil pharmacokinetics, renal tubular reabsorption, and brain penetration in mice. Drug Metab. Dispos. 35: 12091216.
  • Shepherd, E., Lister, N., Affleck, J., Bronk, J., Kellett, G., Collier, I., Bailey, P., Boyd, C. A. (2002) Identification of a candidate membrane protein for the basolateral peptide transporter of rat small intestine. Biochem. Biophys. Res. Commun. 296: 918922.
  • Shu, C., Shen, H., Hopfer, U., Smith, D. E. (2001) Mechanism of intestinal absorption and renal reabsorption of an orally active ACE inhibitor: uptake and transport of fosinopril in cell cultures. Drug Metab. Dispos. 29: 13071315.
  • Silbernagl, S., Ganapathy, V., Leibach, F. H. (1987) H+ gradient-driven dipeptide reabsorption in proximal tubule of rat kidney. Studies in vivo and in vitro. Am. J. Physiol. 253: F448F457.
  • Smith, D. E., Johanson, C. E., Keep, R. F. (2004) Peptide and peptide analog transport systems at the blood-CSF barrier. Adv. Drug Delivery Rev. 56: 17651791.
  • Snyder, N. J., Tabas, L. B., Berry, D. M., Duckworth, D. C., Spry, D. O., Dantzig, A. H. (1997) Structure-activity relationship of carbacephalosporins and cephalosporins: antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells. Antimicrob. Agents Chemother. 41: 16491657.
  • Song, X., Lorenzi, P. L., Landowski, C. P., Vig, B. S., Hilfinger, J. M., Amidon, G. L. (2005a) Amino acid ester prodrugs of the anti-cancer agent gemcitabine: synthesis, bioconversion, metabolic bioevasion, and hPEPT1-mediated transport. Mol. Pharmacol. 2: 157167.
  • Song, X., Vig, B. S., Lorenzi, P. L., Drach, J. C., Townsend, L. B., Amidon, G. L. (2005b) Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter. J. Med. Chem. 48: 12741277.
  • Stark, M., Jornvall, H., Johansson, J. (1999) Isolation and characterization of hydrophobic polypeptides in human bile. Eur. J. Biochem. 266: 209214.
  • Steffansen, B., Nielsen, C. U., Brodin, B., Eriksson, A. H., Andersen, R., Frokjaer, S. (2004) Intestinal solute carriers: an overview of trends and strategies for improving oral drug absorption. Eur. J. Pharm. Sci. 21: 316.
  • Steffansen, B., Nielsen, C. U., Frokjaer, S. (2005) Delivery aspects of small peptides and substrates for peptide transporters. Eur. J. Pharm. Biopharm. 60: 241245.
  • Steiner, H. Y., Naider, F., Becker, J. M. (1995) The PTR family: a new group of peptide transporters. Mol. Microbiol. 16: 825834.
  • Steinhardt, H. J., Adibi, S. A. (1986) Kinetics and characteristics of absorption from an equimolar mixture of 12 glycyl-dipeptides in human jejunum. Gastroenterology 90: 577582.
  • Su, Y., Sinko, P. J. (2006) Drug delivery across the blood-brain barrier: why is it difficult? How to measure and improve it Expert Opin. Drug Deliv. 3: 419435.
  • Sugawara, M., Huang, W., Fei, Y. J., Leibach, F. H., Ganapathy, V., Ganapathy, M. E. (2000) Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J. Pharm. Sci. 89: 781789.
  • Sugawara, M., Ogawa, T., Kobayashi, M., Miyazaki, K. (2003) Uptake of dipeptide and ß-lactam antibiotics by the basolateral membrane vesicles prepared from rat kidney. Biochim. Biophys. Acta. 1609: 3944.
  • Swaan, P. W., Stehouwer, M. C., 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: 3138.
  • Tamai, I., Nakanishi, T., Hayashi, K., Terao, T., Sai, Y., Shiraga, T., Miyamoto, K., Takeda, E., Higashida, H., Tsuji, A. (1997) The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of ß-lactam antibiotics in the rat small intestine. J. Pharm. Pharmacol. 49: 796801.
  • Tamai, I., Nakanishi, T., Nakahara, H., Sai, Y., Ganapathy, V., Leibach, F. H., Tsuji, A. (1998) Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1. J. Pharm. Sci. 87: 15421546.
  • Taub, M. E., Moss, B. A., Steffansen, B., Frokjaer, S. (1998) Oligopeptide transporter mediated uptake and transport of D-Asp(OBzl)-Ala, D-Glu(OBzl)-Ala and D-Ser(Bzl)-Ala in filter-grown Caco-2 monolayers. Int. J. Pharm. 174: 223232.
  • Terada, T., Inui, K. (2004) Peptide transporters: structure, function, regulation and application for drug delivery. Curr. Drug Metab. 5: 8594.
  • Terada, T., Saito, H., Mukai, M., Inui, K. I. (1996) Identification of the histidine residues involved in substrate recognition by a rat H+/peptide cotransporter, PEPT1. FEBS Lett. 394: 196200.
  • Terada, T., Saito, H., Mukai, M., Inui, K. (1997a) Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of ß-lactam antibiotics. J. Pharmacol. Exp. Ther. 281: 14151421.
  • Terada, T., Saito, H., Mukai, M., Inui, K. (1997b) Recognition of ß-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am. J. Physiol. 273: F706F711.
  • Terada, T., Saito, H., Inui, K. (1998) Interaction of β-lactam antibiotics with histidine residue of rat H+/peptide cotransporters, PEPT1 and PEPT2. J. Biol. Chem. 273: 55825585.
  • Terada, T., Sawada, K., Saito, H., Hashimoto, Y., Inui, K. (1999) Functional characteristics of basolateral peptide transporter in the human intestinal cell line Caco-2. Am. J. Physiol. 276: G1435G1441.
  • Terada, T., Saito, H., Sawada, K., Hashimoto, Y., Inui, K. (2000a) N-terminal halves of rat H+/peptide transporters are responsible for their substrate recognition. Pharm. Res. 17: 1520.
  • Terada, T., Sawada, K., Irie, M., Saito, H., Hashimoto, Y., Inui, K. (2000b) Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2. Pflügers Arch. 440: 679684.
  • Terada, T., Sawada, K., Ito, T., Saito, H., Hashimoto, Y., Inui, K. (2000c) Functional expression of novel peptide transporter in renal basolateral membranes. Am. J. Physiol. 279: F851F857.
  • Terada, T., Sawada, K., Saito, H., Hashimoto, Y., Inui, K. (2000d) Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur. J. Pharmacol. 392: 1117.
  • Terada, T., Irie, M., Okuda, M., Inui, K. (2004) Genetic variant Arg57His in human H+/peptide cotransporter 2 causes a complete loss of transport function. Biochem. Biophys. Res. Commun. 316: 416420.
  • Teuscher, N. S., Novotny, A., Keep, R. F., Smith, D. E. (2000) Functional evidence for presence of PEPT2 in rat choroid plexus: studies with glycylsarcosine. J. Pharmacol. Exp. Ther. 294: 494499.
  • Teuscher, N. S., Keep, R. F., Smith, D. E. (2001) PEPT2-mediated uptake of neuropeptides in rat choroid plexus. Pharm. Res. 18: 807813.
  • Teuscher, N. S., Shen, H., Shu, C., Xiang, J., Keep, R. F., Smith, D. E. (2004) Carnosine uptake in rat choroid plexus primary cell cultures and choroid plexus whole tissue from PEPT2 null mice. J. Neurochem. 89: 375382.
  • Thamotharan, M., Lombardo, Y. B., Bawani, S. Z., 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: 1178611790.
  • Theis, S., Hartrodt, B., Kottra, G., Neubert, K., Daniel, H. (2002a) Defining minimal structural features in substrates of the H+/peptide cotransporter PEPT2 using novel amino acid and dipeptide derivatives. Mol. Pharmacol. 61: 214221.
  • Theis, S., Knütter, I., Hartrodt, B., Brandsch, M., Kottra, G., Neubert, K., Daniel, H. (2002b) Synthesis and characterization of high-affinity inhibitors of the H+/peptide transporter PEPT2. J. Biol. Chem. 277: 72877292.
  • Thwaites, D. T., Anderson C. M. (2007) H+-coupled nutrient, micro-nutrient and drug transporters in the mammalian small intestine. Exp. Physiol. 92: 603619.
  • Thwaites, D. T., Hirst, B. H., Simmons, N. L. (1994) 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: 10501056.
  • Thwaites, D. T., Cavet, M., Hirst, B. H., Simmons, N. L. (1995) Angiotensin-converting enzyme (ACE) inhibitor transport in human intestinal epithelial (Caco-2) cells. Br. J. Pharmacol. 114: 981986.
  • Thwaites, D. T., Ford, D., Glanville, M., Simmons, N. L. (1999) H+/solute-induced intracellular acidification leads to selective activation of apical Na+/H+ exchange in human intestinal epithelial cells. J. Clin. Invest. 104: 629635.
  • Thwaites, D. T., Kennedy, D. J., Raldua, D., Anderson, C. M., Mendoza, M. E., Bladen, C. L., Simmons, N. L. (2002) H+/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na+/H+ exchanger. Gastroenterology 122: 13221333.
  • Tomita, Y., Katsura, T., Okano, T., Inui, K., Hori, R. (1990) Transport mechanisms of bestatin in rabbit intestinal brush-border membranes: role of H+/dipeptide cotransport system. J. Pharmacol. Exp. Ther. 252: 859862.
  • Tsuda, M., Terada, T., Irie, M., Katsura, T., Niida, A., Tomita, K., Fujii, N., Inui, K. (2006) Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J. Pharmacol. Exp. Ther. 318: 455460.
  • Tsuji, A. (1999) Tissue selective drug delivery utilizing carrier-mediated transport systems. J. Control. Release 62: 239244.
  • Tsuji, A., Tamai, I., Hirooka, H., Terasaki, T. (1987) β-lactam antibiotics and transport via the dipeptide carrier system across the intestinal brush-border membrane. Biochem. Pharmacol. 36: 565567.
  • Tsuji, A., Tamai, I., Nakanishi, M., Amidon, G. L. (1990) Mechanism of absorption of the dipeptide alpha-methyldopa-phe in intestinal brush-border membrane vesicles. Pharm. Res. 7: 308309.
  • Tsuji, A., Tamai, I., Nakanishi, M., Terasaki, T., Hamano, S. (1993) Intestinal brush-border transport of the oral cephalosporin antibiotic, cefdinir, mediated by dipeptide and monocarboxylic acid transport systems in rabbits. J. Pharm. Pharmacol. 45: 996998.
  • Uchiyama, T., Kulkarni, A. A., Davies, D. L., Lee, V. H. (2003) Biophysical evidence for His57 as a proton-binding site in the mammalian intestinal transporter hPepT1. Pharm. Res. 20: 19111916.
  • Uebel, S., Kraas, W., Kienle, S., Wiesmuller, K. H., Jung, G., Tampe, R. (1997) Recognition principle of the TAP transporter disclosed by combinatorial peptide libraries. Proc. Natl Acad. Sci. USA 94: 89768981.
  • Ugolev, A. M. (1971) Membrane digestion and peptide transport. Ciba Found. Symp. 1971, 23143.
  • Vabeno, J., Lejon, T., Nielsen, C. U., Steffansen, B., Chen, W., Ouyang, H., Borchardt, R. T., Luthman, K. (2004) Phe-Gly dipeptidomimetics designed for the di-/tripeptide transporters PEPT1 and PEPT2: synthesis and biological investigations. J. Med. Chem. 47: 10601069.
  • Vernaleken, A., Veyhl, M., Gorboulev, V., Kottra, G., Palm, D., Burckhardt, B. C., Burckhardt, G., Pipkorn, R., Beier, N., Van Amsterdam, C., Koepsell, H. (2007) Tripeptides of RS1 (RSC1A1) inhibit a monosaccharide-dependent exocytotic pathway of Na+-D-glucose cotransporter SGLT1 with high affinity. J. Biol. Chem. 282: 2850128513.
  • Vig, B. S., Stouch, T. R., Timoszyk, J. K., Quan, Y., Wall, D. A., Smith, R. L., Faria, T. N. (2006) Human PEPT1 pharmacophore distinguishes between dipeptide transport and binding. J. Med. Chem. 49: 36363644.
  • Wanchana, S., Yamashita, F., Hara, H., Fujiwara, S., Akamatsu, M., Hashida, M. (2004) Two- and three-dimensional QSAR of carrier-mediated transport of β-lactam antibiotics in Caco-2 cells. J. Pharm. Sci. 93: 30573065.
  • Weitz, D., Harder, D., Casagrande, F., Fotiadis, D., Obrdlik, P., Kelety, B., Daniel, H. (2007) Functional and structural characterization of a prokaryotic peptide transporter with features similar to mammalian PEPT1. J. Biol. Chem. 282: 28322839.
  • Wenzel, U., Thwaites, D. T., Daniel, H. (1995) Stereoselective uptake of β-lactam antibiotics by the intestinal peptide transporter. Br. J. Pharmacol. 116: 30213027.
  • Wenzel, U., Gebert, I., Weintraut, H., Weber, W. M., Clauss, W., 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: 831839.
  • Whitaker, C. J., Battah, S. H., Forsyth, M. J., Edwards, C., Boyle, R. W., Matthews, E. K. (2000) Photosensitization of pancreatic tumour cells by delta-aminolaevulinic acid esters. Anticancer Drug Des. 15: 161170.
  • Yamashita, T., Shimada, S., Guo, W., Sato, K., Kohmura, E., Hayakawa, T., Takagi, T., Tohyama, M. (1997) Cloning and functional expression of a brain peptide/histidine transporter. J. Biol. Chem. 272: 1020510211.
  • Yeung, A. K., Basu, S. K., Wu, S. K., Chu, C., Okamoto, C. T., Hamm-Alvarez, S. F., Von Grafenstein, H., Shen, W. C., Kim, K. J., Bolger, M. B., Haworth, I. S., Ann, D. K., Lee, V. H. (1998) Molecular identification of a role for tyrosine 167 in the function of the human intestinal proton-coupled dipeptide transporter (hPEPT1). Biochem. Biophys. Res. Commun. 250: 103107.
  • Yuasa, H., Fleisher, D., Amidon, G. L. (1994) Noncompetitive inhibition of cephradine uptake by enalapril in rabbit intestinal brush-border membrane vesicles: an enalapril specific inhibitory binding site on the peptide carrier. J. Pharmacol. Exp. Ther. 269: 11071111.
  • Zhang, E. Y., Fu, D. J., Pak, Y. A., Stewart, T., Mukhopadhyay, N., Wrighton, S. A., Hillgren, K. M. (2004) Genetic polymorphisms in human proton-dependent dipeptide transporter PEPT1: implications for the functional role of Pro586. J. Pharmacol. Exp. Ther. 310: 437445.
  • Zhou, X., Thamotharan, M., Gangopadhyay, A., Serdikoff, C., Adibi, S. A. (2000) Characterization of an oligopeptide transporter in renal lysosomes. Biochim. Biophys. Acta. 1466: 372378.
  • Zhu, T., Chen, X. Z., Steel, A., Hediger, M. A., Smith, D. E. (2000) Differential recognition of ACE inhibitors in Xenopus laevis oocytes expressing rat PEPT1 and PEPT2. Pharm. Res. 17: 526532.
  • Zlokovic, B. V. (1995) Cerebrovascular permeability to peptides: manipulations of transport systems at the blood-brain barrier. Pharm. Res. 12: 13951406.