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Uptake, production and metabolism of cysteinyl leukotrienes in the isolated perfused rat liver. Inhibition of leukotriene uptake by cyclosporine.
Biochem J. 1989 Jul 15; 261(2):611-6.BJ

Abstract

1. The isolated perfused rat liver efficiently takes up cysteinyl leukotrienes (LTs) C4, D4, E4 and N-acetyl-LTE4 from circulation. More than 70% of these cysteinyl LTs are excreted from liver into bile within 1 h of onset of a 5 min infusion, while about 5% remain in the liver. About 20% of infused N-acetyl-LTE4 escapes hepatic first-pass extraction under our conditions. 2. Metabolites of LTC4 appearing in bile within 20 min of the onset of infusion include mainly LTD4 and N-acetyl-LTE4, but also omega-hydroxy-N-acetyl-LTE4 and omega-carboxy-N-acetyl-LTE4. Metabolites generated from omega-carboxy-N-acetyl-LTE4 by beta-oxidation from the omega-end represent the major biliary LTs secreted at later times. 3. Stimulation of the isolated perfused liver by the combined infusion of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 results in a transient increase of endogenous cysteinyl LT production, which is independent of extrahepatic cells. 4. The immunosuppressive drug cyclosporine causes a dose-dependent inhibition of hepatobiliary cysteinyl LT excretion, probably by interference with the sinusoidal uptake system for cysteinyl LTs.

Authors+Show Affiliations

Deutsches Krebsforschungszentrum, Heidelberg, 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

2549977

Citation

Hagmann, W, et al. "Uptake, Production and Metabolism of Cysteinyl Leukotrienes in the Isolated Perfused Rat Liver. Inhibition of Leukotriene Uptake By Cyclosporine." The Biochemical Journal, vol. 261, no. 2, 1989, pp. 611-6.
Hagmann W, Parthé S, Kaiser I. Uptake, production and metabolism of cysteinyl leukotrienes in the isolated perfused rat liver. Inhibition of leukotriene uptake by cyclosporine. Biochem J. 1989;261(2):611-6.
Hagmann, W., Parthé, S., & Kaiser, I. (1989). Uptake, production and metabolism of cysteinyl leukotrienes in the isolated perfused rat liver. Inhibition of leukotriene uptake by cyclosporine. The Biochemical Journal, 261(2), 611-6.
Hagmann W, Parthé S, Kaiser I. Uptake, Production and Metabolism of Cysteinyl Leukotrienes in the Isolated Perfused Rat Liver. Inhibition of Leukotriene Uptake By Cyclosporine. Biochem J. 1989 Jul 15;261(2):611-6. PubMed PMID: 2549977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Uptake, production and metabolism of cysteinyl leukotrienes in the isolated perfused rat liver. Inhibition of leukotriene uptake by cyclosporine. AU - Hagmann,W, AU - Parthé,S, AU - Kaiser,I, PY - 1989/7/15/pubmed PY - 1989/7/15/medline PY - 1989/7/15/entrez SP - 611 EP - 6 JF - The Biochemical journal JO - Biochem J VL - 261 IS - 2 N2 - 1. The isolated perfused rat liver efficiently takes up cysteinyl leukotrienes (LTs) C4, D4, E4 and N-acetyl-LTE4 from circulation. More than 70% of these cysteinyl LTs are excreted from liver into bile within 1 h of onset of a 5 min infusion, while about 5% remain in the liver. About 20% of infused N-acetyl-LTE4 escapes hepatic first-pass extraction under our conditions. 2. Metabolites of LTC4 appearing in bile within 20 min of the onset of infusion include mainly LTD4 and N-acetyl-LTE4, but also omega-hydroxy-N-acetyl-LTE4 and omega-carboxy-N-acetyl-LTE4. Metabolites generated from omega-carboxy-N-acetyl-LTE4 by beta-oxidation from the omega-end represent the major biliary LTs secreted at later times. 3. Stimulation of the isolated perfused liver by the combined infusion of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 results in a transient increase of endogenous cysteinyl LT production, which is independent of extrahepatic cells. 4. The immunosuppressive drug cyclosporine causes a dose-dependent inhibition of hepatobiliary cysteinyl LT excretion, probably by interference with the sinusoidal uptake system for cysteinyl LTs. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/2549977/Uptake_production_and_metabolism_of_cysteinyl_leukotrienes_in_the_isolated_perfused_rat_liver__Inhibition_of_leukotriene_uptake_by_cyclosporine_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/bj2610611 DB - PRIME DP - Unbound Medicine ER -