Publication: Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics
Issued Date
2003-03-28
Resource Type
ISSN
00142999
Other identifier(s)
2-s2.0-10744219672
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
European Journal of Pharmacology. Vol.465, No.1-2 (2003), 1-7
Suggested Citation
Suparat Khamdang, Michio Takeda, Ellappan Babu, Rie Noshiro, Maristela Lika Onozato, Akihiro Tojo, Atsushi Enomoto, Xiu Lin Huang, Shinichi Narikawa, Naohiko Anzai, Pawinee Piyachaturawat, Hitoshi Endou Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics. European Journal of Pharmacology. Vol.465, No.1-2 (2003), 1-7. doi:10.1016/S0014-2999(03)01381-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/21033
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics
Other Contributor(s)
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. © 2003 Elsevier Science B.V. All rights reserved.