title: Uptake of dipeptide and beta-lactam antibiotics by the basolateral membrane vesicles prepared from rat kidney.
abstract: The transport of dipeptides and beta-lactam antibiotics across the rat renal basolateral membrane was examined. The initial uptake of glycylsarcosine and cefadroxil by rat renal basolateral membrane vesicles was inhibited by the presence of all the di- and tripeptides and beta-lactam antibiotics that were tested in this study. However, the uptake of both substrates was not inhibited by glycine, an amino acid. The initial uptake of zwitterionic beta-lactam antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded glycylsarcosine (countertransport effect). On the other hand, the uptake of dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected. A concentration-dependent initial uptake of glycylsarcosine and cefadroxil suggested the existence of a carrier-mediated mechanism, whereas the transport of ceftibuten did not show any saturated uptake. The transporter that participates in the permeation of dipeptides and beta-lactam antibiotics across basolateral membranes showed lower affinity than did PEPT1 and PEPT2. This is the first study that showed an evidence for a peptide transporter, expressed in the rat renal basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using basolateral membrane vesicles isolated from normal rat kidney.
authors.affiliation: Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Toru
authors.initials: T
authors.lastname: Ogawa
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001485:Basement Membrane / Q000201:enzymology / Q000378:metabolism; D001692:Biological Transport; D004151:Dipeptides / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; D047090:beta-Lactams; D000254:Sodium-Potassium-Exchanging ATPase