title: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1.
abstract: This study was performed to elucidate the possible involvement of organic anion transporter 3 (OAT3) in cephaloridine (CER)-induced nephrotoxicity and compare the substrate specificity between rOAT3 and rat OAT1 (rOAT1) for various cephalosporin antibiotics, using proximal tubule cells stably expressing rOAT3 (S2 rOAT3) and rOAT1 (S2 rOAT1). S2 rOAT3 exhibited a CER uptake and a higher susceptibility to CER cytotoxicity than did mock, which was recovered by probenecid. Various cephalosporin antibiotics significantly inhibited both estrone sulfate uptake in S2 rOAT3 and para-aminohippuric acid uptake in S2 rOAT1. The Ki values of CER, cefoperazone, cephalothin and cefazolin for rOAT3- and rOAT1-mediated organic anion transport ranged from 0.048 to 1.14 mM and from 0.48 to 1.32 mM, respectively. These results suggest that rOAT3, at least in part, mediates CER uptake and CER-induced nephrotoxicity as rOAT1. There was some difference of affinity between rOAT3 and rOAT1 for cephalosporin antibiotics.
authors: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan. endouh@kyorin-u.ac.jp
authors: Kyu Yong
authors: KY
authors: Jung
authors: Michio
authors: M
authors: Takeda
authors: Minoru
authors: M
authors: Shimoda
authors: Shinichi
authors: S
authors: Narikawa
authors: Akihiro
authors: A
authors: Tojo
authors: Do Kyung
authors: DK
authors: Kim
authors: Arthit
authors: A
authors: Chairoungdua
authors: Bong Kyu
authors: BK
authors: Choi
authors: Hiroyuki
authors: H
authors: Kusuhara
authors: Yuichi
authors: Y
authors: Sugiyama
authors: Takashi
authors: T
authors: Sekine
authors: Hitoshi
authors: H
authors: Endou
mesh_terms: D000818:Animals; D002509:Cephaloridine / Q000633:toxicity*; D002511:Cephalosporins / Q000633:toxicity*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects*; D051379:Mice; D029362:Organic Anion Transporters, Sodium-Independent / Q000032:analysis / Q000502:physiology*; D051381:Rats
chemical_list: D002511:Cephalosporins; D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; C421143:Slco1a5 protein, rat; D002509:Cephaloridine