| Uptake, production and metabolism of cysteinyl leukotrienes in the isolated perfused rat liver. Inhibition of leukotriene uptake by cyclosporine. | |
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MedLine Citation:
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PMID: 2549977 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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W Hagmann; S Parthé; I Kaiser |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 261 ISSN: 0264-6021 ISO Abbreviation: Biochem. J. Publication Date: 1989 Jul |
Date Detail:
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Created Date: 1989-10-12 Completed Date: 1989-10-12 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 611-6 Citation Subset: IM |
Affiliation:
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Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cyclosporins / pharmacology* Leukotriene E4 Liver / drug effects, metabolism* Male Perfusion Rats Rats, Inbred Strains SRS-A / analogs & derivatives, biosynthesis, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cyclosporins; 0/SRS-A; 75715-89-8/Leukotriene E4; 80115-95-3/N-acetylleukotriene E4 |
| Comments/Corrections | |
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