Wettstein M, Gerok W, Häussinger D
Medizinische Universitätsklinik Freiburg, Federal Republic of Germany.
Eur J Biochem. 1990 Jul 20;191(1):251-5. doi: 10.1111/j.1432-1033.1990.tb19117.x.
In single-pass perfused rat liver, the sinusoidal uptake of infused 3H-labelled leukotriene (LT) C4 (10 nmol.l-1) was inhibited by sulfobromophthalein. Inhibition was half-maximal at sulfobromophthalein concentrations of approximately 1.2 mumol.l-1 in the influent perfusate and leukotriene uptake was inhibited by maximally 34%. Sulfobromophthalein (20 mumol.l-1) also decreased the uptake of infused [3H]LTE4 (10 nmol.l-1) by 31%. Indocyanine green (10 mumol.l-1) inhibited the sinusoidal [3H]LTC4 uptake by 19%. Replacement of sodium in the perfusion medium by choline decreased the uptake of infused [3H]LTC4 (10 nmol.l-1) by 56%, but was without effect on the uptake of sulfobromophthalein. The canalicular excretion of LTC4, LTD4 and N-acetyl-LTE4 was inhibited by sulfobromophthalein. In contrast, the proportion of polar omega-oxidation metabolites recovered in bile following the infusion of [3H]LTC4 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 LTD4 recovered in bile increased at the expense of LTC4. Following the infusion of [3H]LTD4 (10 nmol.l-1), a major biliary metabolite was LTC4 indicating a reconversion of LTD4 to LTC4. In the presence of taurocholate (40 mumol.l-1), however, this reconversion was completely inhibited. The findings suggest the involvement of different transport systems in the sinusoidal uptake of cysteinyl leukotrienes. LTC4 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 LTC4, LTD4 and N-acetyl-LTE4, but not with the excretion of omega-oxidized cysteinyl leukotrienes. The data may be relevant for the understanding of hepatic leukotriene processing in conditions like hyperbilirubinemia or cholestasis.
在单通道灌注大鼠肝脏中，注入的3H标记白三烯（LT）C4（10 nmol·L-1）的窦状隙摄取受到磺溴酞的抑制。在流入灌注液中磺溴酞浓度约为1.2 μmol·L-1时抑制作用达到半数最大，白三烯摄取最大被抑制34%。磺溴酞（20 μmol·L-1）也使注入的[3H]LTE4（10 nmol·L-1）摄取减少31%。吲哚菁绿（10 μmol·L-1）使窦状隙[3H]LTC4摄取减少19%。用胆碱替代灌注液中的钠使注入的[3H]LTC4（10 nmol·L-1）摄取减少56%，但对磺溴酞摄取无影响。磺溴酞抑制LTC4、LTD4和N-乙酰-LTE4的胆小管排泄。相反，注入[3H]LTC4后胆汁中回收的极性ω-氧化代谢物比例增加。牛磺胆酸盐对窦状隙白三烯摄取无影响，但增加胆汁流量以及摄取的放射性物质的胆汁清除。随着牛磺胆酸盐添加量增加，胆汁中回收的LTD4量增加，而LTC4量减少。注入[3H]LTD4（10 nmol·L-1）后，一种主要的胆汁代谢物是LTC4，表明LTD4可再转化为LTC4。然而，在牛磺胆酸盐（40 μmol·L-1）存在时，这种再转化被完全抑制。这些发现提示不同转运系统参与了半胱氨酰白三烯的窦状隙摄取。LTC4摄取不受胆汁酸影响，有钠依赖性和非钠依赖性成分，后者可能与有机染料共用。磺溴酞也干扰LTC4、LTD4和N-乙酰-LTE4的胆小管转运，但不影响ω-氧化半胱氨酰白三烯的排泄。这些数据可能有助于理解高胆红素血症或胆汁淤积等情况下肝脏白三烯的处理过程。
