Uptake of the mycotoxin ochratoxin A in liver cells occurs via the cloned organic anion transporting polypeptide.

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Kontaxi M, Echkardt U, Hagenbuch B, Stieger B, Meier PJ, Petzinger E

Uptake of the mycotoxin ochratoxin A in liver cells occurs via the cloned organic anion transporting polypeptide.

J Pharmacol Exp Ther. 1996 Dec;279(3):1507-13.

PubMed ID

8968376 [ View in PubMed

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Abstract

Ochratoxin A (OTA) is a mycotoxin produced by mold. It mainly causes nephropathies in humans and domestic animals as a major pathogenic contaminant of cereals and animal feed. Upon p.o. uptake and intestinal absorption, a large part of OTA is taken up by hepatocytes and eliminated into bile. In the present study, hepatocellular uptake of radiolabeled [3H]OTA in isolated rat hepatocytes was characterized; a saturable (K(m) = 18.9 microM, Vmax = 473 pmol/mg/min), temperature (Aapp = 30.4 and 76.6 kilo Joule/mol) and energy-dependent mycotoxin transport was found. This OTA uptake was inhibited by various bile acids, sulfobromophthalein and the thrombin inhibitor CRC 220. Because all inhibitors are substrates of the organic anion-transporting polypeptide (oatp), a recently cloned hepatic carrier, uptake experiments were performed in oatp-cRNA-injected Xenopus laevis oocytes. These studies revealed an oatp-specific OTA uptake (K(m) = 16.6 microM). In contrast, OTA was not transported by the hepatic Na+/taurocholate-cotransporting polypeptide. Known oatp substrates cis-inhibited OTA uptake in oatp-cRNA-injected oocytes in close correlation with the results derived from isolated hepatocytes. These results identify OTA as a new substrate for oatp. They further support the multispecific nature of oatp-mediated transport and stress the importance of this carrier for hepatic clearance of xenobiotics.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Conjugated estrogens	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Substrate Inhibitor	Details
Taurocholic acid	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Substrate Inhibitor Inducer	Details