Role of human organic anion transporter 4 in the transport of ochratoxin A.

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Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H

Role of human organic anion transporter 4 in the transport of ochratoxin A.

Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75.

PubMed ID

12063169 [ View in PubMed

]

Abstract

The purpose of this study was to investigate the characteristics of ochratoxin A (OTA) transport by multispecific human organic anion transporter 4 (hOAT4) using mouse proximal tubule cells stably transfected with hOAT4 (S(2) hOAT4). Immunohistochemical analysis revealed that hOAT4 protein was localized to the apical side of the proximal tubule. S(2) hOAT4 expressed hOAT4 protein in the apical side as well as basolateral side and the cells were cultured on the plastic dish for experiments. S(2) hOAT4 exhibited a time- and concentration-dependent, and a saturable increase in OTA uptake, with an apparent K(m) value of 22.9+/-2.44 microM. The OTA uptakes were inhibited by several substrates for the OATs. Probenecid, piroxicam, octanoate and citrinin inhibited OTA uptake by hOAT4 in a competitive manner (K(i)=44.4-336.4 microM), with the following order of potency: probenecid > piroxicam > octanoate >citrinin. The efflux of OTA by S(2) hOAT4 was higher than that by mock. Addition of OTA resulted in slight decrease in viability of S(2) hOAT4 compared with mock. These results indicate that hOAT4 mediates the high-affinity transport of OTA on the apical side of the proximal tubule, whereas the transport characteristics of OTA are distinct from those by basolateral OATs.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Probenecid	Solute carrier family 22 member 11	Protein	Humans	Yes	Inhibitor	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Aminohippuric acid	Solute carrier family 22 member 11	Protein	Humans	Unknown	Substrate Inhibitor	Details
Aspartame	Solute carrier family 22 member 11	Protein	Humans	Unknown	Inhibitor	Details
Benzylpenicillin	Solute carrier family 22 member 11	Protein	Humans	Unknown	Inhibitor	Details
Caprylic acid	Solute carrier family 22 member 11	Protein	Humans	Unknown	Inhibitor	Details
Indomethacin	Solute carrier family 22 member 11	Protein	Humans	Unknown	Inhibitor	Details
Piroxicam	Solute carrier family 22 member 11	Protein	Humans	Unknown	Inhibitor	Details
Probenecid	Solute carrier family 22 member 11	Protein	Humans	Unknown	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Caprylic acid	Solute carrier family 22 member 11	Ki (nM)	235500	N/A	N/A	Details
Piroxicam	Solute carrier family 22 member 11	Ki (nM)	107800	N/A	N/A	Details
Probenecid	Solute carrier family 22 member 11	Ki (nM)	44400	N/A	N/A	Details