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The mechanism for the cellular extrusion of sulfated conjugates is still unknown. In the present study, we investigated whether human wild type ABCG2 transports estrone 3-sulfate (E1S) using membrane vesicles from cDNA-transfected mouse lymphoma cell line (P388 cells). The uptake of 3HE1S into ABCG2-expressing membrane vesicles was stimulated by ATP, and the Km value for 3HE1S was determined to be 16.6 microm. The ABCG2-mediated transport of 3HE1S was potently inhibited by SN-38 and many sulfate conjugates but not by glucuronide and glutathione conjugates or other anionic compounds. Other sulfate conjugates such as 3Hdehydroepiandrosterone sulfate (DHEAS) and 35S4-methylumbelliferone sulfate (Km = 12.9 microm) and 35S6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole (E3040) sulfate (Km = 26.9 microm) were also transported by ABCG2. Although 3Hmethotrexate, 3H17beta-estradiol-17beta-D-glucuronide, 3H2,4-dinitrophenyl-S-glutathione, and 14C4-methylumbelliferone glucuronide were transported by ABCG2, this took place to a much lesser extent compared with 3HE1S. It was suggested that ABCG2 preferentially transports sulfate conjugates and that E1S and DHEAS are the potential physiological substrates for this transporter.
Suzuki et al. (Sun,) studied this question.