Elsevier

Life Sciences

Volume 69, Issue 18, 21 September 2001, Pages 2123-2135
Life Sciences

Original articles
Characterization of ochratoxin A transport by human organic anion transporters

https://doi.org/10.1016/S0024-3205(01)01296-6Get rights and content

Abstract

The purpose of this study was to investigate the characteristics of ochratoxin A (OTA) transport by multispecific human organic anion transporters (hOAT1 and hOAT3, respectively) using the second segment of proximal tubule (S2) cells from mice stably expressing hOAT1 and hOAT3 (S2 hOAT1 and S2 hOAT3). S2 hOAT1 and S2 hOAT3 exhibited a time- and dose-dependent, and a saturable increase in uptake of [3H]-OTA, with apparent Km values of 0.42 μM (hOAT1) and 0.75 μM (hOAT3). These OTA uptakes were inhibited by several substrates for the OATs. Para-aminohippuric acid (PAH), probenecid, piroxicam, octanoate and citrinin inhibited [3H]-OTA uptake by hOAT1 and hOAT3 in a competitive manner (Ki = 4.29∼3080 μM), with the following order of potency: probenecid > octanoate > PAH > piroxicam > citrinin for hOAT1; probenecid > piroxicam > octanoate> citrinin > PAH for hOAT3. These 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 substrates for the OATs. These pharmacological characteristics of hOAT1 and hOAT3 may be significantly related with the events in the development of OTA-induced nephrotoxicity in the human kidney.

References (0)

Cited by (92)

  • Investigating the interaction between organic anion transporter 1 and ochratoxin A: An in silico structural study to depict early molecular events of substrate recruitment and the impact of single point mutations

    2022, Toxicology Letters
    Citation Excerpt :

    The set of ligands included, along with OTA, 6-carboxyfluorescein, para-aminohippuric acid and prostaglandin E2 (Fig. 3). As reported in the USCD-FDA TransPortal database, all these ligands have been already described as high affinity substrates of OAT1 with Km values in the low μM range (Cihlar and Ho, 2000; Islinger et al., 2001; Jung et al., 2001; Kimura et al., 2002). The set of decoys was collected from the scientific literature and included homostachydrine, glycitein-7-glucuronide, pravastatin and beta-muricholate (Fig. 3) as previous studies ascertained that they are not appreciably transported or bound by OAT1 (Bush et al., 2017; Takeda et al., 2004; Wong et al., 2011).

  • Uptake Transporters

    2018, Comprehensive Toxicology: Third Edition
View all citing articles on Scopus
View full text