title: Functional integrity of hepatocyte canalicular membrane transport of taurocholate and bilirubin diglucuronide in Eisai hyperbilirubinuria rats.
abstract: Eisai hyperbilirubinuria rats (EHBR) are characterized by conjugated hyperbilirubinemia, and impaired or defective excretion of bilirubin, reduced glutathione and other organic anions from hepatocytes. Hepatocyte canalicular membrane vesicles (CMV) from EHBR and normal SD rats were studied with regard to taurocholate (TC) transport driven by ATP or a membrane potential and bicarbonate-stimulated bilirubin diglucuronide (BDG) transport. ATP-dependent uptake or association of BDG with CMV was also studied in both strains of rats. No significant differences in the uptake of TC and BDG by CMV were observed. This indicates the functional integrity of the canalicular transporters for both organic anions in EHBR. Biliary excretion of taurolithocholic acid sulfate (TLCS) is defective in EHBR. However, TLCS inhibited ATP-dependent TC uptake by SD rat CMV competitively, which may be against the hypothesis that a common organic anion carrier is defective in canalicular membranes of jaundiced rats.
authors.affiliation: Second Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Shouji
authors.forename: M
authors.initials: M
authors.lastname: Kitano
authors.forename: Y
authors.initials: Y
authors.lastname: Okuyama
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism* / Q000648:ultrastructure; D001663:Bilirubin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine*; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006933:Hyperbilirubinemia, Hereditary / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000378:metabolism*; D013658:Taurolithocholic Acid / Q000494:pharmacology
chemical_list: C019270:bilirubin diglucuronide; D013658:Taurolithocholic Acid; D013656:Taurocholic Acid; D001663:Bilirubin