title: Bilitranslocase is involved in the uptake of bromosulfophthalein in rat and human liver.
abstract: Hepatic disposition of bromosulfophthalein (BSP), bilirubin and bile salts partially overlap, as these anions share both uptake and excretion mechanisms. Multiple organic anion transporters mediate hepatic BSP uptake, i.e. members of the SLCO and SLC22 gene families and bilitranslocase (TCDB #2.A.65.1.1). This study aimed at evaluating the relative contribution of bilitranslocase in BSP uptake in precision-cut human and rat liver slices. To this purpose, two different anti-sequence bilitranslocase antibodies were used as specific, functional inhibitors of bilitranslocase. The intact liver physiology was accurately reproduced in this BSP uptake assay, since uptake was strongly temperature-dependentand inhibited by hepatotropic organic anions, such as 50 nM bilirubin, 1 μM nicotinic acid, 2 μM digoxin, 5 μMindocyanine green and 100 μM taurocholate. The bilitranslocase antibodies inhibited BSP uptake both in rat and human liver slices. The combined use of bilitranslocase antibodies and taurocholate caused additive-type inhibition, confirming that bilitranslocase is not a bile salt transporter; by contrast, bilirubin caused no additive-type inhibition. In conclusion this data, indicate the role of the bilirubin transporter bilitranslocase as one of the transporters involved in the uptake of anions like BSP in parallel with other organic anion carriers. Moreover this data indicate the value of precision-cut liver slices for phenotypic drug uptake studies.
authors.affiliation: Department of Life Sciences, University of Trieste, via L. Giorgieri, 1, 34127 Trieste, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Terdoslavich
authors.forename: Inge A M
authors.initials: IA
authors.lastname: de Graaf
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Proost
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cocolo
authors.forename: Sabina
authors.initials: S
authors.lastname: Passamonti
authors.forename: Geny M M
authors.initials: GM
authors.lastname: Groothuis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001692:Biological Transport; D002570:Ceruloplasmin; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013448:Sulfobromophthalein / Q000493:pharmacokinetics*; D013656:Taurocholic Acid / Q000378:metabolism; D013696:Temperature
chemical_list: D000906:Antibodies; D008565:Membrane Proteins; D013448:Sulfobromophthalein; D013656:Taurocholic Acid; D002570:Ceruloplasmin; C033838:bilitranslocase