title: Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat.
abstract: Biliary secretion of 3 alpha-sulfated bile acids has been studied in Wistar rats with an autosomal recessive defect in the hepatic transport of bilirubin. Liver function, established by measurement of various enzymes in plasma, by enzyme histochemical methods, and by electron microscopy, appeared to be normal in these rats. Serum levels of unconjugated, monoglucuronidated, and diglucuronidated bilirubin were 0.62, 1.62, and 6.16 mumol/liter, respectively, compared with 0.17, 0.08, and 0.02 mumol/liter in control rats. Biliary bilirubin secretion was strongly reduced in the mutant animals: 0.21 +/- 0.03 vs. 0.39 +/- 0.03 nmol/min per 100 g body wt in control rats. Despite normal biliary bile acid output, bile flow was markedly impaired in the mutant animals, due to a 53% reduction of the bile acid-independent fraction of bile flow. The transport maximum for biliary secretion of dibromosulphthalein (DBSP) was also drastically reduced (-53%). Biliary secretion of intravenously administered trace amounts of the 3 alpha-sulfate esters of 14C-labeled taurocholic acid (-14%), taurochenodeoxycholic acid (-39%), taurolithocholic acid (-73%), and glycolithocholic acid (-91%) was impaired in the jaundiced rats compared with controls, in contrast to the biliary secretion of the unsulfated parent compounds. Hepatic uptake of sulfated glycolithocholic acid was not affected in the jaundiced animals. Preadministration of DBSP (15 mumol/100 g body wt) to normal Wistar rats significantly impaired the biliary secretion of sulfated glycolithocholic acid, but did not affect taurocholic acid secretion. We conclude that separate transport systems in the rat liver exist for biliary secretion of sulfated and unsulfated bile acids; the sulfates probably share secretory pathways with the organic anions bilirubin and DBSP. The described genetic defect in hepatic transport function is associated with a reduced capacity to secrete sulfated bile acids into bile; this becomes more pronounced with a decreasing number of hydroxyl groups on the sulfated bile acid's molecule.
authors: Department of Pediatrics, University of Groningen, The Netherlands.
authors: F
authors: F
authors: Kuipers
authors: M
authors: M
authors: Enserink
authors: R
authors: R
authors: Havinga
authors: A B
authors: AB
authors: van der Steen
authors: M J
authors: MJ
authors: Hardonk
authors: J
authors: J
authors: Fevery
authors: R J
authors: RJ
authors: Vonk
mesh_terms: D000818:Animals; D001646:Bile / Q000502:physiology; D001647:Bile Acids and Salts / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D001692:Biological Transport; D006651:Histocytochemistry; D008095:Lithocholic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008111:Liver Function Tests; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013448:Sulfobromophthalein / Q000031:analogs & derivatives / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism; D013658:Taurolithocholic Acid / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D013448:Sulfobromophthalein; C012479:dibromosulphthalein; D013655:Taurochenodeoxycholic Acid; D013658:Taurolithocholic Acid; D013656:Taurocholic Acid; D008095:Lithocholic Acid; C027746:glycolithocholic acid; D001663:Bilirubin