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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.
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M Enserink, and
R Havinga, and
A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
August 1979,
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M J Hardonk, and
J Fevery, and
R J Vonk
November 1987,
Biochimica et biophysica acta,
F Kuipers, and
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A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
January 1984,
Hepatology (Baltimore, Md.),
F Kuipers, and
M Enserink, and
R Havinga, and
A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
May 1987,
Journal of lipid research,
F Kuipers, and
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A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
February 1971,
Proceedings of the National Academy of Sciences of the United States of America,
F Kuipers, and
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January 1992,
Pharmacological research,
F Kuipers, and
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A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
October 2000,
Pharmacological research,
F Kuipers, and
M Enserink, and
R Havinga, and
A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
April 1952,
North Carolina medical journal,
F Kuipers, and
M Enserink, and
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A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
January 1988,
Annals of clinical research,
F Kuipers, and
M Enserink, and
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A B van der Steen, and
M J Hardonk, and
J Fevery, and
R J Vonk
December 1988,
Clinical and experimental pharmacology & physiology,
