Transport PepTl

Wenzel, U., Gebert, I., Weintraut, H., Weber, W.-M., Clauss, W., Daniel, H., Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepTl and in human intestinal Caco-2 cells, J. Pharmacol. Exp. Ther. 1996, 277, 831-839. 

Shiraga, T., Miyamoto, K., Tanaka, H., Yamamoto, H., Taketani, Y. et al, Cellular and molecular mechanisms of dietary regulation on rat intestinal H+/Peptide transporter PepTl, Gastroenterology 1999, 3 36, 354-362. 

Brodin, B., et al. Transport of peptidomimetic drugs by the intestinal Di/tri-peptide transporter, PepTl. Pharmacol. Toxicol. 2002, 90, 285-296. 

Tamai, I., et al. The predominant contribution of oligopeptide transporter PepTl to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J. Pharm. Pharmacol. 

Doring, F., S. Theis, and H. Daniel. Expression and functional characterization of the mammalian intestinal peptide transporter PepTl in the methylotropic yeast Pichia pastoris. Biochem. Biophys. Res. Commun. 1997, 232, 656-662. 

Balimane, P. V., et al. Direct evidence for peptide transporter (PepTl)-mediated uptake of a nonpeptide prodrug, valacyclovir. Biochem. 

Some drugs with low intrinsic permeability achieve acceptable oral bioavailability because they are substrates for uptake transporters, which normally function in nutrient uptake. The most prominent example is the peptide transporter, PepTl, which is active toward peptidomimetic antibiotics such as cephalexin, the antiviral agent valacyclovir [24] and other drugs. PepTl is natively expressed in Caco-2 cells, and adenovirus transduction has been used to increase PepTl expression levels [25]. However, the expression of PepTl was not polarized in this system and this expressed system appears to be of limited value as an improved screening model. PepTl has also been expressed in Chinese hamster ovary cells and a variety of other mammalian systems [26, 27]. 

Cellular and molecular mechanisms of dietary regulation on rat intestinal H+/Peptide transporter PepTl, Gastroenterology 1999, 116, 354-362. 

Thomsen, A. E., Friedrichsen, G., Sorensen, A. H., Andersen, R., Nielsen, C. U., Brodin, B., Begtrup, M., Frokjaer, S., Steffansen, B., Prodrugs of purine and pyrimidine analogues for the intestinal di/ tripeptide transporter PepTl affinity... 

F. H., Tsuji, A., Improvement of L-dopa absorption by dipeptidyl derivation utilizing peptide transporter PepTl,/. Pharm. Sci. 1998, 87, 1542-1546. 

Wang, H., Ganapathy, V., Valad-dovir a substrate for the intestinal and renal peptide transporters PepTl and PepT2, Biochem. Biophys. Res. Commun. 1998, 246, 470—475. 

Hydrophilic peptides and proteins are frequently large molecules they may enter the brain by carrier-mediated transport, receptor-mediated transcytosis, or by adsorptive-mediated transcytosis. Small peptides, such as di- and tripeptides are transported by the specific transporters, PepTl and PepT2, but neither of them is present at the BBB. Nevertheless, there is saturable brain uptake of the tripeptide glutathione and of several opioid peptides, suggesting that specific transporters, as... 

In a recent review of pharmacokinetics in drug discovery, Ruiz-Garcia et al. [81] compiled an exhaustive list of software resources for absorption prediction. The main topic in the described databases is transporters, in particular the ATP-binding cassette, of which the efflux transporter P-gp and the peptide transporter PEPTl are well known examples. These examples show that science is moving away from the simplistic passive transport view of permeability and towards an all-inclusive, mechanism-understanding model of absorption, which takes account of all the interactions between the agents involved in the specific permeation process. 

Behrens, 1., Kamm,W., Dantzig,A.H. and Kissel, T. (2004) Variation of peptide transporter PepTl and HPTl expression in Caco-2 cells as a frmction of cell origin. Journal of Pharmaceutical Sciences, 93, 1743-1754. 

Exceptions from Lipinski s rule, i.e., molecules of PSA values > 140 A2 are found to be actively absorbed by carrier-mediated transport systems (Wessel et al. 1998), as shown in Fig. 3. IB. As further detailed in Fig. 3.2, the intestinal epithelium expresses a number of such transport systems for amino acids, organic anions and cations, nucleosides, and hexoses. Among these systems are the apical sodium-dependent bile acid transporter (ASBT Annaba et al. 2007), the monocarboxylate transporter (MCT Halestrap and Price 1999), the sodium-D-glucose co-transporter (SFGT1 Kipp et al. 2003), and the nucleotide transporter SPNT1 (Balimane and Sinko 1999). In addition, the expression of a specialized transporter system for small peptides has been found in the intestinal epithelium with the di/tripeptide transporter, PepTl (Tsuji 2002), after previous functional studies by Hu et al. (1989), and the cloning of PepTl... 

Brodin B, Nielsen CU, Steffansen B, Frokjaer S (2002) Transport of peptidomimetic drugs by the intestinal di/tripeptide transporter, PepTl. Pharmacol Toxicol 90 285-296 Bry L, Falk P, Huttner K, Ouellette A, Midtvedt T, Gordon JI (1994) Paneth cell differentiation in the developing intestine of normal and transgenic mice. Proc Natl Acad Sci 91 10335-10339... 

After the break down of proteins by proteolytic enzymes, the pancreas, and brush border peptidases, the di- and trip-eptides are absorbed through the epithelial cell membrane. Many studies have shown that intact di- and tripeptides are absorbed across the epithelial cell membrane by active transport via specific carrier systems. The absorption process is mediated by the hydrogen-coupled peptide transporter (PEPTl) located in the intestinal apical cell membrane. Because there are 20 amino acids, there may be 400... 

Meredith, D., Temple, C.S., Guha, N., Sword, C.J., Boyd, C.A., Collier, I.D., Morgan, K.M. and Bailey, P.D. (2000) Modified amino acids and peptides as substrates for the intestinal peptide transporter PepTl. European Journal of Biochemistry, 267 (12), 3723-3728. 

Ziegler, T.R., Fernandez-Estivariz, C., Gu, L.H., Bazargan, N., Umeakunne, K., Wallace, T.M., Diaz, E.E., Rosado, K.E., Pascal, R.R., Galloway, J.R. et al. (2002) Distribution of the H + /peptide transporter PepTl in human intestine up-regulated expression in the colonic mucosa of patients with short-bowel syndrome. The American Journal of Clinical Nutrition, 75 (5), 922-930. 

Shi, B., Song, D., Xue, H., Li, J. and Li, N. (2006) Abnormal expression of the peptide transporter PepTl in the colon of massive bowel resection rat a potential route for colonic mucosa damage by transport of fMLP. Digestive Diseases and Sciences, 51 (11), 2087-2093. 

Amino acids are absorbed by Na +-dependent transport proteins, with different proteins for acidic, neutral, and anionic amino acids. Small peptides are absorbed by the peptide transporter PEPTl in the brush-border membrane [11]. The PEPTl mRNA pattern exhibits regional differences with duodenum > jejunum > ileum [22]. The carrier works as an H cotransport system and recognizes 2-3-amino acid-long small peptides as well as drugs with peptide-like structures such as renin inhibitors, ACE inhibitors [23], or P-lactam antibiotics (Figure 9.7). It also serves as a target for... 

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