title: Physiological and pharmacological implications of peptide transporters, PEPT1 and PEPT2.
abstract: The H+/peptide co-transporters PEPT1 and PEPT2 mediate the cellular uptake of small peptides and peptide-like drugs from the glomerular filtrates. In the present study, we investigated the physiological and pharmacological implications of both transporters. (i) Comparison of the substrate affinity of PEPT1 and PEPT2 indicated that PEPT2 had higher affinity than PEPT1 for most substrates. (ii) The transport characteristics of beta-lactam antibiotics in the renal brush border membrane vesicles were well correlated with those in a PEPT2-expressing transfectant. These results suggested that PEPT2 predominantly contributed to reabsorption of beta-lactam antibiotics in the kidney at therapeutic concentrations. (iii) In rats with chronic renal failure, glycylsarcosine (Gly-Sar) uptake by the renal brush border membranes vesicles was maintained, whereas Na+-dependent glucose uptake was markedly reduced. It is therefore speculated that the function of peptide transporters is tolerant to chronic renal failure.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inui
authors.forename: T
authors.initials: T
authors.lastname: Terada
authors.forename: S
authors.initials: S
authors.lastname: Masuda
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000042:Absorption; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007769:Lactams; D008562:Membrane Glycoproteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D000074011:Peptide Transporter 1; D051381:Rats; D051269:Sodium-Glucose Transporter 1; D027981:Symporters
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D007769:Lactams; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; C489940:Slc15a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2