title: Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep.
abstract: The bile salt export pump (BSEP) of hepatocyte secretes conjugated bile salts across the canalicular membrane in an ATP-dependent manner. The biliary bile salts of human differ from those of rat in containing a greater proportion of glycine conjugates and taurolithocholate 3-sulfate (TLC-S). In the present study, the transport properties of hBSEP and rBsep were investigated using membrane vesicles from HEK293 cells infected with recombinant adenoviruses containing hBSEP or rBsep cDNA. ATP-dependent uptake of radiolabeled glycine-, taurine-conjugated bile salts, and [(3)H]cholate was observed when hBSEP or rBsep was expressed. Comparison of initial uptake rates indicated that for both transporters, taurine-conjugated bile salts were transported more rapidly than glycine-conjugated bile salts, however, hBSEP transported glycine conjugates to an extent that was approximately 2-fold greater than rBsep. In addition, [(3)H]TLC-S was significantly transported by hBSEP, and hardly transported by rBsep. The mean K(m) value for the uptake of [(3)H]TLC-S by hBSEP was 9.5+/-1.5 microM, a value similar to that for hMRP2 (8.2+/-1.3 microM). In conclusion, both hBSEP and rBsep transport taurine-conjugated bile salts better than glycine-conjugated bile salts, but hBSEP transports glycine conjugates to a greater extent as compared to rBsep. TLC-S, which is present in human bile but not rodent bile, is more avidly transported by hBSEP compared with rBsep.
authors.affiliation: Department of Molecular Biopharmaceutics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Reiko
authors.initials: R
authors.lastname: Onuki
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005998:Glycine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D000089762:Multidrug Resistance-Associated Protein 2; D051381:Rats; D013045:Species Specificity; D013654:Taurine / Q000737:chemistry / Q000378:metabolism; D013656:Taurocholic Acid / Q000493:pharmacokinetics; D013658:Taurolithocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*
chemical_list: C093491:ABCB11 protein, human; C000715087:ABCC2 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; D001647:Bile Acids and Salts; D000089762:Multidrug Resistance-Associated Protein 2; C066776:taurolithocholic acid 3-sulfate; D013654:Taurine; D013658:Taurolithocholic Acid; D013656:Taurocholic Acid; D005998:Glycine