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Stereoselective uptake of β‐lactam antibiotics by the intestinal peptide transporter
Author(s) -
Wenzel Uwe,
Thwaites David T.,
Daniel Hannelore
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15958.x
Subject(s) - transporter , peptide , chemistry , efflux , symporter , oligopeptide , caco 2 , biochemistry , intracellular , xenopus , stereochemistry , cell , gene
1 The stereoselective transport of β‐lactam antibiotics has been investigated in the human intestinal epithelial cell line, Caco‐2, by use of D‐ and L‐enantiomers of cephalexin and loracarbef as substrates. 2 The L‐isomers of cephalexin, loracarbef and dipeptides displayed a higher affinity for the oligopeptide/H + ‐symporter in Caco‐2 cells than the D‐isomers. This was demonstrated by inhibition of the influx of the β‐lactam, [ 3 H]‐cefadroxil. 3 By measurement of the substrate‐induced intracellular acidification in Caco‐2 cells loaded with the pH‐sensitive fluorescent dye BCECF (2′,7′‐ bis (2‐carboxyethyl)‐5‐(6)‐carboxy‐fluorescein), it was demonstrated for the first time that L‐isomers of β‐lactams not only bind to the peptide transporter with high affinity but are indeed transported. 4 Efficient proton‐coupled transport of L‐β‐lactam antibiotics was also shown to occur in Xenopus laevis oocytes expressing the cloned peptide transporter PepTl from rabbit small intestine. 5 Both cell systems therefore express a stereoselective transport pathway for β‐lactam antibiotics with very similar characteristics and may prove useful for screening rapidly the oral availability of peptide‐derived drugs.