title: ABCG2 transports sulfated conjugates of steroids and xenobiotics.
abstract: 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 [3H]E1S into ABCG2-expressing membrane vesicles was stimulated by ATP, and the Km value for [3H]E1S was determined to be 16.6 microm. The ABCG2-mediated transport of [3H]E1S 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 [3H]dehydroepiandrosterone sulfate (DHEAS) and [35S]4-methylumbelliferone sulfate (Km = 12.9 microm) and [35S]6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole (E3040) sulfate (Km = 26.9 microm) were also transported by ABCG2. Although [3H]methotrexate, [3H]17beta-estradiol-17beta-D-glucuronide, [3H]2,4-dinitrophenyl-S-glutathione, and [14C]4-methylumbelliferone glucuronide were transported by ABCG2, this took place to a much lesser extent compared with [3H]E1S. It was suggested that ABCG2 preferentially transports sulfate conjugates and that E1S and DHEAS are the potential physiological substrates for this transporter.
authors.affiliation: School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D019314:Dehydroepiandrosterone Sulfate / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007700:Kinetics; D008223:Lymphoma; D051379:Mice; D009363:Neoplasm Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D013256:Steroids / Q000493:pharmacokinetics*; D013464:Sulfuric Acids / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D013256:Steroids; D013464:Sulfuric Acids; D015262:Xenobiotics; D019314:Dehydroepiandrosterone Sulfate