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Hereditary defect of hepatobiliary cysteinyl leukotriene elimination in mutant rats with defective hepatic anion excretion
Author(s) -
Huber Michael,
Guhlmann Albrecht,
Jansen Peter L. M.,
Keppler Dietrich
Publication year - 1987
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840070204
Subject(s) - leukotriene , medicine , enterohepatic circulation , endocrinology , chemistry , metabolite , excretion , leukotriene e4 , leukotriene c4 , urine , leukotriene b4 , gastrointestinal tract , biliary tract , metabolism , biology , asthma , inflammation
Hepatobiliary and renal elimination of cysteinyl leu‐kotrienes were investigated in a mutant rat strain with a hereditary defect in the hepatobiliary excretion of conjugated bilirubin, dibromosulfophthalein and oua‐bain. After intravenous injection of [ 3 H]leukotriene C 4 , the initial half‐life of radioactivity circulating in blood was 79 ± 15 sec (S.D.) in transport mutant rats as compared to 31 ± 6 sec (S.D.) in normal Wistar rats. The intrahepatic leukotriene radioactivity was increased 5‐fold after 1 hr in mutant rats, while the biliary elimination of [ 3 H]Ieukotrienes was reduced to 1.8% of control. In normal rats, 77 ± 7% (S.D.) of the administered leukotriene radioactivity were recovered in bile within 1 hr. The total recovery of radioactivity from bile, urine, liver, intestine, stomach, kidneys, muscular system and blood 1 hr after intravenous [ 3 H]leukotriene C 4 was 89 ± 6% (S.D.) in normal rats and 46 ± 4% (S.D.) in transport mutants. Enterohepatic circulation was studied after intraduodenal administration of N ‐acetyl‐[ 3 H]leukotriene E 4 , a major cysteinyl leukotriene metabolite in rat bile. In transport mutants, hepatobiliary elimination of the intestinally absorbed [ 3 H]leukotriene was reduced to 5%, whereas urinary excretion was not significantly affected. [ 3 H]Leukotriene metabolites in bile, liver and urine were separated by reversed‐phase high‐performance liquid chromatography. The proportion of N ‐acetyl‐[ 3 H]leukotriene E 4 relative to polar leukotriene metabolites was higher in the bile of transport mutants as compared to control Wistar rats when analyzed within 30 to 60 min after intravenous injection of [ 3 H]leukotriene C 4 . Our results indicate that the cysteinyl leukotrienes are physiological substrates of the can‐alicular transport system for organic anions such as dibromosulfophthalein. The transport mutant rats serve to characterize the hepatobiliary excretion system for cysteinyl leukotrienes.