Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1.

Article Details

Citation

Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H

Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1.

Life Sci. 2002 Mar 8;70(16):1861-74.

PubMed ID
12005172 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CefacetrileSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefacetrileSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefadroxilSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefadroxilSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefalotinSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefalotinSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefamandoleSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefamandoleSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefazolinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefazolinSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefoperazoneSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefoperazoneSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefotaximeSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefotaximeSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CeftriaxoneSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CeftriaxoneSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CephalexinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CephalexinSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details