Multispecific substrate recognition of kidney-specific organic anion transporters OAT-K1

We characterized the interactions of various compounds with OAT-K1 and OAT-K2, kidney-specific organic anion transport-ers. By using Madin-Darby canine kidney cells stably trans-fected with OAT-K1 or OAT-K2 cDNA, the antitumor drug meth-otrexate, the mycotoxin ochratoxin A, endogenous organic anions (thyroid hormones, taurocholic acid, and conjugated steroids), and the antiretroviral drug zidovudine were shown to be substrates for these transporters. Although the apparent Michaelis constant (Km) values of methotrexate for OAT-K1 and OAT-K2 were 2.1 and 1.8 M, respectively, 2.5 mM methotrex-ate inhibited only 20 % of the 125I-thyroid hormones uptake via these transporters. In addition, 100 M methotrexate did not have any effect on [3H]zidovudine uptake via OAT-K1 or OAT-K2. Similarly, several substrates caused little or no mutua