Characteristics of sinusoidal uptake and biliary excretion of cysteinyl leukotrienes in perfused rat liver

In single‐pass perfused rat liver, the sinusoidal uptake of infused 3 H‐labelled leukotriene (LT) C 4 (10nmol · 1 −1 ) was inhibited by sulfobromophthalein. Inhibition was half‐maximal at sulfobromophthalein concentrations of approximately 1.2 μmol · 1 −1 in the influent perfusate and leukotriene uptake was inhibited by maximally 34% Sulfobromophthalein (20 μmol · 1 −1 ) also decreased the uptake of infused [ 3 H]LTE 4 (10 nmol · 1 −1 ) by 31%. Indocyanine green (10 μmol · 1 −1 ) inhibited the sinusoidal [ 3 H]LTC 4 uptake by 19%. Replacement of sodium in the perfusion medium by choline decreased the uptake of infused [ 3 H]LTC 4 (10 nmol · 1 −1 ) by 56%, but was without effect on the uptake of sulfobromophthalein. The canalicular excretion of LTC 4 , LTD 4 and N ‐acetyl‐LTE 4 was inhibited by sulfobromophthalein. In contrast, the proportion of polar ω‐oxidation metabolites recovered in bile following the infusion of [ 3 H]LTC 4 was increased. Taurocholate, which had no effect on the sinusoidal leukotriene uptake, increased bile flow and also the biliary elimination of the radioactivity taken up. With increasing taurocholate additions, the amount of LTD 4 recovered in bile increased at the expense of LTC 4 . Following the infusion of [ 3 H]LTD 4 (10 nmol · 1 −1 ), a major biliary metabolite was LTC 4 indicating a reconversion of LTD 4 to LTC 4 . In the presence of taurocholate (40 μmol · 1 −1 ), however, this reconversion was completely inhibited. The findings suggest the involvement of different transport systems in the sinusoidal uptake of cysteinyl leukotrienes. LTC 4 uptake is not affected by bile acids and has a sodium‐dependent and a sodium‐independent component, the latter probably being shared with organic dyes. Sulfobromophthalein also interferes with the canalicular transport of LTC 4 , LTD 4 and N ‐acetyl‐LTE 4 , but not with the excretion of ω‐oxidized cysteinyl leukotrienes. The data may be relevant for the understanding of hepatic leukotriene processing in conditions like hyperbilirubinemia or cholestasis.