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Characteristics of sinusoidal uptake and biliary excretion of cysteinyl leukotrienes in perfused rat liver.
Eur J Biochem. 1990 Jul 20; 191(1):251-5.EJ

Abstract

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.

Authors+Show Affiliations

Medizinische Universitätsklinik Freiburg, Federal Republic of Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2165907

Citation

Wettstein, M, et al. "Characteristics of Sinusoidal Uptake and Biliary Excretion of Cysteinyl Leukotrienes in Perfused Rat Liver." European Journal of Biochemistry, vol. 191, no. 1, 1990, pp. 251-5.
Wettstein M, Gerok W, Häussinger D. Characteristics of sinusoidal uptake and biliary excretion of cysteinyl leukotrienes in perfused rat liver. Eur J Biochem. 1990;191(1):251-5.
Wettstein, M., Gerok, W., & Häussinger, D. (1990). Characteristics of sinusoidal uptake and biliary excretion of cysteinyl leukotrienes in perfused rat liver. European Journal of Biochemistry, 191(1), 251-5.
Wettstein M, Gerok W, Häussinger D. Characteristics of Sinusoidal Uptake and Biliary Excretion of Cysteinyl Leukotrienes in Perfused Rat Liver. Eur J Biochem. 1990 Jul 20;191(1):251-5. PubMed PMID: 2165907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characteristics of sinusoidal uptake and biliary excretion of cysteinyl leukotrienes in perfused rat liver. AU - Wettstein,M, AU - Gerok,W, AU - Häussinger,D, PY - 1990/7/20/pubmed PY - 1990/7/20/medline PY - 1990/7/20/entrez SP - 251 EP - 5 JF - European journal of biochemistry JO - Eur J Biochem VL - 191 IS - 1 N2 - 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. SN - 0014-2956 UR - https://www.unboundmedicine.com/medline/citation/2165907/Characteristics_of_sinusoidal_uptake_and_biliary_excretion_of_cysteinyl_leukotrienes_in_perfused_rat_liver_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1990&volume=191&issue=1&spage=251 DB - PRIME DP - Unbound Medicine ER -