Dipeptide transporters

Snyder NJ, Tabas LB, Berry DM, Duckworth DC, Spry DO and Dantzig AH. 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 1997 41 1649-57. 

Chong, S., S. A. Dando, K. M. Soucek, and R. A. Morrison. In vitro permeability through caco-2 cells is not quantitatively predictive of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system, Pharm. Res. 1996, 13, 120-123... 

Dantzig, A. H., Bergin, L., Uptake of cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2,... 

Ganapathy, V. and F. H. Leibach. Role of pH gradient and membrane potential in dipeptide transport in intestinal and renal brush-border membrane vesicles from the rabbit. Studies with L-camosine and glycyl-L-proline. J. Biol. Chem. 1983, 258, 14189-14192. 

Covitz, K. M., G. L. Amidon, and W. Sadee. Human dipeptide transporter, hPEPTl, stably transfected into Chinese hamster ovary cells. Pharm. Res. 1996, 13, 1631-1634. 

Moore, V. A., et al. A rapid screening system to determine drug affinities for the intestinal dipeptide transporter 2 affinities of ACE inhibitors. Int. J. Pharm. 2000, 210, 29-44. 

Inui, K., et al. H+ coupled active transport of bestatin via the dipeptide transport system in rabbit intestinal brush-border membranes. J. Pharmacol. Exp. Ther. 1992, 260, 482-486. 

Enjoh, M., et al. Inhibitory effect of arphamenine A on intestinal dipeptide transport. Biosci. Biotechnol. Biochem. 1996, 60, 1893-1895. 

Additionally, amino acids may be reclaimed as dipeptides. The transport mechanisms for dipeptides are less specific than those for individual amino acids but require the dipeptide to carry a net positive charge so there is cotransport of protons, rather than of Na+ as for free amino acids. A potential advantage of dipeptide transport process is the favourable cell-lumen concentration gradient, which exists for peptides compared with free amino acids. 

Morimoto K, Yamahara H, Lee VH, Kim K-J (1993) Dipeptide transport across rat alveolar epithelial cell monolayers. Pharm Res 10 1668-1674. 

Yamashita F, Mathias NR, Kim K-J, Lee VHL (1996) Dipeptide transport properties of rabbit tracheal epithelial cell monolayers cultured at an air-liquid interface. PharmRes 15 979-983. 

Radhakrishnan, A. N. 1977. Intestinal dipeptidases and dipeptide transport in the monkey and in man. In Peptide Transport and Hydroly i iba Foundation Symposium, -359. New York Elsevier Science Publishers. 

Helliwell, P.A., D. Meredith, C.A. Boyd, J.R. Bronk, N. Lister, and P.D. Bailey. 1994. Tripeptide transport in rat lung. Biochim. Biophys. Acta 1190 430-434. Meredith, D., and C.A. Boyd. 1995. Dipeptide transport characteristics of the apical membrane of rat lung type II pneumocytes. Am.]. Physiol. 269 L137-L143. 

In valacidovir, the hydroxyl group is es-terified with the amino acid L-valine (p. 287B). This allows utilization of an enteral dipeptide transporter, leading to an enteral absorption rate almost double that of aciclovir. Subsequent cleavage of the valine residue yields aciclovir. 

M. Duckworth, D. C. Spry, D. O., Dantzing, A. Structure-activity relationship of carbacephalosporines and cepha-losporines Antibacterial activity and interaction with intestinal proton-depen-dent dipeptide transport carrier of caco-2 cells. Antimicrobial Agents Chemother. 1997, 41 (8), 1649-1657. 

GuandaElni, S., and Rubino, A. (1982). Development of dipeptide transport in the intestinal mucosa of rabbits. Pediatr. Res. 16, 99-103. 

Human plasma contains more than 60 proteins. There are three main proteins associated with the binding of drugs albumin, AAG, and lipoproteins. This article does will not review drug transport proteins of recent interest such as p-glycoproteins, organic anion transporters, and dipeptide transporters, which have been reviewed recently. 

An active dipeptide transport system that depends on hydrogen ions takes up non-ester amino-beta-lactams (penicillin, amoxicillin, and oral first-generation cephalosporins) (337-339) and specific cephalosporins that lack the alpha-amino group (cefixime, ceftibuten, cefdinir, cef-prozil) (340,341). Nifedipine increases amoxiciUin and cefixime absorption, probably by stimulating the dipeptide transport system, since the serum concentrations of passively absorbed drugs and intestinal blood flow did not change (342-344). 

Matsumoto S, Saito H, Inui K. TransceUular transport of oral cephalosporins in human intestinal epithehal cells, Caco-2 interaction with dipeptide transport systems in apical and basolateral membranes. J Pharmacol Exp Ther 1994 270(2) 498-504. 

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