Uptake, Production and Metabolism of Cysteinyl Leukotrienes in the Isolated Perfused Rat Liver. Inhibition of Leukotriene Uptake by Cyclosporine

Overview

Journal Biochem J

Specialty Biochemistry

Date 1989 Jul 15

PMID 2549977

Citations 4

Authors

W Hagmann

S Parthe

I Kaiser

Affiliations

Soon will be listed here.

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.

Citing Articles

Investigation of MDMA Inhibitory Effect on CytochromeP450 3A4 in Isolated Perfused Rat Liver Model Using Tramadol.

Sheikholeslami B, Tootoonchi Z, Lavasani H, Ardakani Y, Rouini M Adv Pharm Bull. 2021; 11(3):530-536.

PMID: 34513628 PMC: 8421619. DOI: 10.34172/apb.2021.061.

Hepatobiliary excretion of cysteinyl leukotrienes in three experimental models of acute hepatic injury.

Omar H, Sanders R, Watkins 3rd J Inflamm Res. 1996; 45(10):519-23.

PMID: 8912018 DOI: 10.1007/BF02311089.

Cell proliferation status, cytokine action and protein tyrosine phosphorylation modulate leukotriene biosynthesis in a basophil leukaemia and a mastocytoma cell line.

Hagmann W Biochem J. 1994; 299 ( Pt 2):467-72.

PMID: 7513514 PMC: 1138295. DOI: 10.1042/bj2990467.

Hepatic uptake and metabolic disposition of leukotriene B4 in rats.

Hagmann W, Korte M Biochem J. 1990; 267(2):467-70.

PMID: 2159284 PMC: 1131312. DOI: 10.1042/bj2670467.

References

Denzlinger C, Guhlmann A, Scheuber P, Wilker D, Hammer D, Keppler D . Metabolism and analysis of cysteinyl leukotrienes in the monkey. J Biol Chem. 1986; 261(33):15601-6. View

Hagmann W, Denzlinger C, Rapp S, Weckbecker G, Keppler D . Identification of the major endogenous leukotriene metabolite in the bile of rats as N-acetyl leukotriene E4. Prostaglandins. 1986; 31(2):239-51. DOI: 10.1016/0090-6980(86)90050-x. View

McColl S, Hurst N, Cleland L . Modulation by phorbol myristate acetate of arachidonic acid release and leukotriene synthesis by human polymorphonuclear leukocytes stimulated with A23187. Biochem Biophys Res Commun. 1986; 141(2):399-404. DOI: 10.1016/s0006-291x(86)80186-3. View

Dieter P, Altin J, Bygrave F . Possible involvement of prostaglandins in vasoconstriction induced by zymosan and arachidonic acid in the perfused rat liver. FEBS Lett. 1987; 213(1):174-8. DOI: 10.1016/0014-5793(87)81486-2. View

Huber M, Guhlmann A, Jansen P, Keppler D . Hereditary defect of hepatobiliary cysteinyl leukotriene elimination in mutant rats with defective hepatic anion excretion. Hepatology. 1987; 7(2):224-8. DOI: 10.1002/hep.1840070204. View

Hagmann W, Steffan A, KIRN A, Keppler D . Leukotrienes as mediators in frog virus 3-induced hepatitis in rats. Hepatology. 1987; 7(4):732-6. DOI: 10.1002/hep.1840070419. View

Huber M, Keppler D . Inhibition of leukotriene D4 catabolism by D-penicillamine. Eur J Biochem. 1987; 167(1):73-9. DOI: 10.1111/j.1432-1033.1987.tb13305.x. View

Iwai M, Jungermann K . Possible involvement of eicosanoids in the actions of sympathetic hepatic nerves on carbohydrate metabolism and hemodynamics in perfused rat liver. FEBS Lett. 1987; 221(1):155-60. DOI: 10.1016/0014-5793(87)80371-x. View

Samuelsson B, Dahlen S, Lindgren J, Rouzer C, Serhan C . Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987; 237(4819):1171-6. DOI: 10.1126/science.2820055. View

10.

Foster A, Fitzsimmons B, Rokach J, Letts L . Metabolism and excretion of peptide leukotrienes in the anesthetized rat. Biochim Biophys Acta. 1987; 921(3):486-93. DOI: 10.1016/0005-2760(87)90076-2. View

11.

Le Thai B, Dumont M, Michel A, Erlinger S, Houssin D . Cyclosporine-induced cholestasis: inhibition of bile acid secretion is caused by the parental molecule. Transplant Proc. 1987; 19(5):4149-51. View

12.

Foster A, Fitzsimmons B, Rokach J, Letts G . Evidence of in-vivo omega-oxidation of peptide leukotrienes in the rat: biliary excretion of 20-CO2H N-acetyl LTE4. Biochem Biophys Res Commun. 1987; 148(3):1237-45. DOI: 10.1016/s0006-291x(87)80265-6. View

13.

Orning L . Omega-oxidation of cysteine-containing leukotrienes by rat-liver microsomes. Isolation and characterization of omega-hydroxy and omega-carboxy metabolites of leukotriene E4 and N-acetylleukotriene E4. Eur J Biochem. 1987; 170(1-2):77-85. DOI: 10.1111/j.1432-1033.1987.tb13669.x. View

14.

Ziegler K, Polzin G, Frimmer M . Hepatocellular uptake of cyclosporin A by simple diffusion. Biochim Biophys Acta. 1988; 938(1):44-50. DOI: 10.1016/0005-2736(88)90120-4. View

15.

Wolkoff A, Johansen K, Goeser T . The isolated perfused rat liver: preparation and application. Anal Biochem. 1987; 167(1):1-14. DOI: 10.1016/0003-2697(87)90127-8. View

16.

Haussinger D, Stehle T, Decker K, Gerok W . Prostaglandin responses in isolated perfused rat liver: Ca2+ and K+ fluxes, hemodynamic and metabolic effects. Biol Chem Hoppe Seyler. 1987; 368(11):1509-13. DOI: 10.1515/bchm3.1987.368.2.1509. View

17.

Stene D, Murphy R . Metabolism of leukotriene E4 in isolated rat hepatocytes. Identification of beta-oxidation products of sulfidopeptide leukotrienes. J Biol Chem. 1988; 263(6):2773-8. View

18.

Iwai M, Jungermann K . Leukotrienes increase glucose and lactate output and decrease flow in perfused rat liver. Biochem Biophys Res Commun. 1988; 151(1):283-90. DOI: 10.1016/0006-291x(88)90591-8. View

19.

Haussinger D, Gyufko K, Decker K . Stimulation of prostaglandin release by Ca2+-mobilizing agents from the perfused rat liver. A comparative study on the action of ATP, UTP, phenylephrine, vasopressin and nerve stimulation. Biol Chem Hoppe Seyler. 1988; 369(1):65-8. DOI: 10.1515/bchm3.1988.369.1.65. View

20.

Kuiper J, Zijlstra F, Kamps J, Van Berkel T . Identification of prostaglandin D2 as the major eicosanoid from liver endothelial and Kupffer cells. Biochim Biophys Acta. 1988; 959(2):143-52. DOI: 10.1016/0005-2760(88)90025-2. View