ABCG2 transports sulfated conjugates of steroids and xenobiotics.
Article Details
- CitationCopy to clipboard
Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y
ABCG2 transports sulfated conjugates of steroids and xenobiotics.
J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7.
- PubMed ID
- 12682043 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Conjugated estrogens ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Doxorubicin ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Estrone ATP-binding cassette sub-family G member 2 Protein Humans UnknownInhibitorDetails Methotrexate ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Pravastatin ATP-binding cassette sub-family G member 2 Protein Humans NoSubstrateDetails