Characterization of ochratoxin A transport by human organic anion transporters

The purpose of this study was to investigate the characteristics of ochrato xin A (OTA) transport by multispecific human organic anion transporters (hO AT1 and hOAT3, respectively) using the second segment of proximal tubule (S -2) cells from mice stably expressing hOAT1 and hOAT3 (S-2 hOAT1 and S-2 hO AT3). S-2 hOAT1 and S-2 hOAT3 exhibited a time- and dose-dependent, and a s aturable increase in uptake of [H-3]-OTA, with apparent K-m values of 0.42 muM (hOAT1) and 0.75 muM (hOAT3). These OTA uptakes were inhibited by sever al substrates for the OATs. Para-aminohippuric acid (PAH), probenecid, piro xicam, octanoate and citrinin inhibited [H-3]-OTA uptake by hOAT1 and hOAT3 in a competitive manner (K-i = 4.29 similar to 3080 muM), with the followi ng order of potency: probenecid > octanoate > PAH > piroxicam > citrinin fo r hOAT1; probenecid > piroxicam > octanoate > citrinin > PAH for hOAT3. The se results indicate that hOAT1, as well as hOAT3, mediates a high-affinity transport of OTA on the basolateral side of the proximal tubule, but hOAT1- and hOAT3-mediated OTA transport are differently influenced by the substra tes for the OATs. These pharmacological characteristics of hOAT1 and hOAT3 may be significantly related with the events in the development of OTA-indu ced nephrotoxicity in the human kidney. (C) 2001 Elsevier Science Inc. All rights reserved.