title: Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B.
abstract: Human organic anion-transporting polypeptide B (OATP-B; OATP2B1) is expressed in the human intestinal epithelial cells, and is suggested to be involved in the intestinal absorption of anionic drugs in vivo. Although citrus juices have been shown to inhibit the function of human OATP-A (OATP1A2), the effect of citrus juices on the OATP-B function remains unclear. In this study, we aimed to examine the effects of citrus juices on the function of OATP-B. The effects of citrus juices on the uptake of estrone-3-sulfate, a typical substrate for OATP-B, into human embryonic kidney 293 cells stably expressing OATP-B were evaluated. Juices were diluted with uptake buffer, adjusted to pH 7.4 and approximately 300 mOsm, and used for the experiments. Grapefruit juice (GFJ) and orange juice (OJ) at a concentration of 5% significantly inhibited the OATP-B-mediated uptake of estrone-3-sulfate by 82 and 53%, respectively. Major constituents of GFJ and OJ also significantly inhibited the OATP-B-mediated uptake of estrone-3-sulfate. Glibenclamide, a hypoglycemic drug, was identified for the first time as a substrate for OATP-B with a K(t) value of 6.26 microM. GFJ and OJ inhibited the OATP-B-mediated uptake of glibenclamide. These results suggest that citrus juices may inhibit the intestinal absorption of anionic drugs, such as glibenclamide, via the inhibition of OATP-B.
authors.affiliation: Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Satoh
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yamashita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Noriko
authors.initials: N
authors.lastname: Koyabu
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ohtani
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sawada
mesh_terms: D001628:Beverages; D002460:Cell Line; D032083:Citrus paradisi; D032084:Citrus sinensis; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D005905:Glyburide / Q000378:metabolism; D006801:Humans; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
chemical_list: D027361:Organic Anion Transporters; C450859:SLCO2B1 protein, human; D004970:Estrone; C017296:estrone sulfate; D005905:Glyburide