1997 Volume 12 Issue supplement Pages 82-83
PEPT1 and PEPT2 are H+-coupled peptide transporters expressed preferentially in the intestine and kidney, respectively, which mediate uphill transport of oligopeptides and peptide-like drugs such as β-lactam antibiotics. In the present study, we have compared the recognition of β-lactam antibiotics by LLC-PK, cells stably transfected with rat PEPT1 or PEPT2 cDNA. Among the examined drugs, cyclacillin (aminopenicillin) and cefadroxil (aminocephalosporin) showed the most potent inhibitory effects on glycylsarcosine uptake in PEPT1- and PEPT2-expressing cells, respectively. Comparison of the Ki values of β-lactam antibiotics between PEPT1 and PEPT2-expressing cells suggested that PEPT2 had a much higher affinity for β-lactam antibiotics with an α-amino group. We have examined interactions of β-lactam antibiotics with rat renal brush-border membrane vesicles, in which PEPT1 and PEPT2 appeared to be coexpressed. The apparent Ki values of the antibiotics for glycylsarcosine transport were closely correlated with those in the PEPT2-expressing cells, suggesting that β-lactam antibiotics interact predominantly with PEPT2 rather than PEPT1 in renal brush-border membranes. In conclusion, 1) PEPTI and PEPT2 show different recognitions of β-lactam antibiotics, and 2) β-lactam antibiotics predominantly interact with renal PEPT2 at pharmacological concentrations.
