Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics.
Article Details
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Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H
Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics.
Eur J Pharmacol. 2003 Mar 28;465(1-2):1-7.
- PubMed ID
- 12650826 [ View in PubMed]
- Abstract
Cephalosporin antibiotics are thought to be excreted into the urine via organic anion transporters (OATs) and OAT can mediate nephrotoxicity by cephalosporins, particularly by cephaloridine. The purpose of this study was to elucidate the interaction of human-OAT2 and rat-OAT2 with cephalosporin antibiotics using proximal tubule cells stably expressing human-OAT2 and rat-OAT2. Human-OAT2 is localized to the basolateral side of the proximal tubule, whereas rat-OAT2 is localized to the apical side of the proximal tubule. Cephalosporins tested were cephalothin, cefoperazone, cefazolin, ceftriaxone, cephaloridine, cefotaxime, cefadroxil and cefamandole. These cephalosporins dose-dependently inhibited organic anion uptake mediated by human-OAT2 and rat-OAT2. There was no species difference observed for the effects of OAT2 with cephalosporins between human and rat transporters. Kinetic analysis revealed that the inhibitory effects for human-OAT2 were competitive. Cephaloridine significantly decreased the viability of cells stably expressing human-OAT2, human-OAT1, human-OAT3 and human-OAT4. The decreased viability of cells stably expressing human-OAT1, human-OAT3 and human-OAT4 but not human-OAT2 was reversed by probenecid. In conclusion, human-OAT2 interacts with cephalosporins, and thus, human-OAT2 may mediate the uptake of cephalosporins on the basolateral side of the proximal tubule. The interaction of human-OAT2 with cephalosporins was the weakest among the basolateral human-OATs tested. In addition, it is suggested that human-OATs mediate cephaloridine-induced nephrotoxicity.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Cefotaxime Solute carrier family 22 member 7 Protein Humans UnknownNot Available Details - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cefalotin Solute carrier family 22 member 7 Protein Humans UnknownInhibitorDetails Cefamandole Solute carrier family 22 member 7 Protein Humans UnknownInhibitorDetails Cefoperazone Solute carrier family 22 member 7 Protein Humans UnknownInhibitorDetails Cefotaxime Solute carrier family 22 member 7 Protein Humans UnknownInhibitorDetails Degraded Cephaloridine Solute carrier family 22 member 11 Protein Humans UnknownNot Available Details Degraded Cephaloridine Solute carrier family 22 member 6 Protein Humans UnknownNot Available Details Degraded Cephaloridine Solute carrier family 22 member 8 Protein Humans UnknownNot Available Details - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Cefalotin Solute carrier family 22 member 7 IC 50 (nM) 1410000 N/A N/A Details Cefamandole Solute carrier family 22 member 7 IC 50 (nM) 1570000 N/A N/A Details Cefoperazone Solute carrier family 22 member 7 IC 50 (nM) 1330000 N/A N/A Details Cefotaxime Solute carrier family 22 member 7 IC 50 (nM) 4680000 N/A N/A Details