Abstract
Experiments on the metabolism and excretion of i.v. administered selectively labeled [3H8]leukotriene C4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D4. By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D4 concentrations from 10 +/- 1 to 86 +/- 10 nM (mean +/- SEM, n = 5, P less than 0.001). When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D4 in bile increased from 0.88 +/- 0.16 before to 3.18 +/- 0.38 pmol X min-1 X kg-1 after challenge (mean +/- SEM, n = 5, P less than 0.002). It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C4 (up to 1 nmol/kg during a 30-min period after the challenge.
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Selected References
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- Aehringhaus U., Peskar B. A., Wittenberg H. R., Wölbling R. H. Effect of inhibition of synthesis and receptor antagonism of SRS-A in cardiac anaphylaxis. Br J Pharmacol. 1983 Sep;80(1):73–80. doi: 10.1111/j.1476-5381.1983.tb11051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andersson P. Effects of inhibitors of anaphylactic mediators in two models of bronchial anaphylaxis in anaesthetized guinea-pigs. Br J Pharmacol. 1982 Oct;77(2):301–307. doi: 10.1111/j.1476-5381.1982.tb09299.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Appelgren L. E., Hammarström S. Distribution and metabolism of 3H-labeled leukotriene C3 in the mouse. J Biol Chem. 1982 Jan 10;257(1):531–535. [PubMed] [Google Scholar]
- Bernström K., Hammarström S. A novel leukotriene formed by transpeptidation of leukotriene E. Biochem Biophys Res Commun. 1982 Dec 15;109(3):800–804. doi: 10.1016/0006-291x(82)92010-1. [DOI] [PubMed] [Google Scholar]
- Dahlén S. E., Hansson G., Hedqvist P., Björck T., Granström E., Dahlén B. Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1712–1716. doi: 10.1073/pnas.80.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dahlén S. E., Palmertz U., Hedqvist P. Methylprednisolone inhibition of leukotriene-dependent airway anaphylaxis in the guinea pig in vivo. Agents Actions. 1986 Jan;17(3-4):310–311. doi: 10.1007/BF01982630. [DOI] [PubMed] [Google Scholar]
- Denzlinger C., Guhlmann A., Scheuber P. H., Wilker D., Hammer D. K., Keppler D. Metabolism and analysis of cysteinyl leukotrienes in the monkey. J Biol Chem. 1986 Nov 25;261(33):15601–15606. [PubMed] [Google Scholar]
- Denzlinger C., Rapp S., Hagmann W., Keppler D. Leukotrienes as mediators in tissue trauma. Science. 1985 Oct 18;230(4723):330–332. doi: 10.1126/science.4048937. [DOI] [PubMed] [Google Scholar]
- Ferreri N. R., Howland W. C., Spiegelberg H. L. Release of leukotrienes C4 and B4 and prostaglandin E2 from human monocytes stimulated with aggregated IgG, IgA, and IgE. J Immunol. 1986 Jun 1;136(11):4188–4193. [PubMed] [Google Scholar]
- Feuerstein G. Autonomic pharmacology of leukotrienes. J Auton Pharmacol. 1985 Jun;5(2):149–168. doi: 10.1111/j.1474-8673.1985.tb00116.x. [DOI] [PubMed] [Google Scholar]
- Feuerstein G. Leukotrienes and the cardiovascular system. Prostaglandins. 1984 May;27(5):781–802. doi: 10.1016/0090-6980(84)90015-7. [DOI] [PubMed] [Google Scholar]
- Fleisch J. H., Rinkema L. E., Haisch K. D., Swanson-Bean D., Goodson T., Ho P. P., Marshall W. S. LY171883, 1-less than 2-hydroxy-3-propyl-4-less than 4-(1H-tetrazol-5-yl) butoxy greater than phenyl greater than ethanone, an orally active leukotriene D4 antagonist. J Pharmacol Exp Ther. 1985 Apr;233(1):148–157. [PubMed] [Google Scholar]
- Hagmann W., Denzlinger C., Keppler D. Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. Circ Shock. 1984;14(4):223–235. [PubMed] [Google Scholar]
- 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 Feb;31(2):239–251. doi: 10.1016/0090-6980(86)90050-x. [DOI] [PubMed] [Google Scholar]
- Hammarström S. Leukotrienes. Annu Rev Biochem. 1983;52:355–377. doi: 10.1146/annurev.bi.52.070183.002035. [DOI] [PubMed] [Google Scholar]
- Hammarström S. Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver, and kidney. J Biol Chem. 1981 Sep 25;256(18):9573–9578. [PubMed] [Google Scholar]
- Hammarström S., Orning L., Bernström K. Metabolism of leukotrienes. Mol Cell Biochem. 1985 Nov;69(1):7–16. doi: 10.1007/BF00225922. [DOI] [PubMed] [Google Scholar]
- Hua X. Y., Dahlén S. E., Lundberg J. M., Hammarström S., Hedqvist P. Leukotrienes C4, D4 and E4 cause widespread and extensive plasma extravasation in the guinea pig. Naunyn Schmiedebergs Arch Pharmacol. 1985 Aug;330(2):136–141. doi: 10.1007/BF00499906. [DOI] [PubMed] [Google Scholar]
- Lefer A. M. Eicosanoids as mediators of ischemia and shock. Fed Proc. 1985 Feb;44(2):275–280. [PubMed] [Google Scholar]
- Lefer A. M. Leukotrienes as mediators of ischemia and shock. Biochem Pharmacol. 1986 Jan 15;35(2):123–127. doi: 10.1016/0006-2952(86)90502-2. [DOI] [PubMed] [Google Scholar]
- Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis R. A., Drazen J. M., Austen K. F., Toda M., Brion F., Marfat A., Corey E. J. Contractile activities of structural analogs of leukotrienes C and D: role of the polar substituents. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4579–4583. doi: 10.1073/pnas.78.7.4579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lux W. E., Jr, Feuerstein G., Faden A. I. Thyrotropin-releasing hormone reverses the hypotension and bradycardia produced by leukotriene D4 in unanesthetized guinea pigs. Prostaglandins Leukot Med. 1983 Mar;10(3):301–307. doi: 10.1016/0262-1746(82)90085-3. [DOI] [PubMed] [Google Scholar]
- MacGlashan D. W., Jr, Schleimer R. P., Peters S. P., Schulman E. S., Adams G. K., Sobotka A. K., Newball H. H., Lichtenstein L. M. Comparative studies of human basophils and mast cells. Fed Proc. 1983 May 15;42(8):2504–2509. [PubMed] [Google Scholar]
- Ormstad K., Uehara N., Orrenius S., Orning L., Hammarström S. Uptake and metabolism of leukotriene C3 by isolated rat organs and cells. Biochem Biophys Res Commun. 1982 Feb 26;104(4):1434–1440. doi: 10.1016/0006-291x(82)91410-3. [DOI] [PubMed] [Google Scholar]
- Orning L., Kaijser L., Hammarström S. In vivo metabolism of leukotriene C4 in man: urinary excretion of leukotriene E4. Biochem Biophys Res Commun. 1985 Jul 16;130(1):214–220. doi: 10.1016/0006-291x(85)90404-8. [DOI] [PubMed] [Google Scholar]
- Orning L., Norin E., Gustafsson B., Hammarström S. In vivo metabolism of leukotriene C4 in germ-free and conventional rats. Fecal excretion of N-acetylleukotriene E4. J Biol Chem. 1986 Jan 15;261(2):766–771. [PubMed] [Google Scholar]
- Razin E., Mencia-Huerta J. M., Stevens R. L., Lewis R. A., Liu F. T., Corey E., Austen K. F. IgE-mediated release of leukotriene C4, chondroitin sulfate E proteoglycan, beta-hexosaminidase, and histamine from cultured bone marrow-derived mouse mast cells. J Exp Med. 1983 Jan 1;157(1):189–201. doi: 10.1084/jem.157.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rouzer C. A., Scott W. A., Hamill A. L., Liu F. T., Katz D. H., Cohn Z. A. Secretion of leukotriene C and other arachidonic acid metabolites by macrophages challenged with immunoglobulin E immune complexes. J Exp Med. 1982 Oct 1;156(4):1077–1086. doi: 10.1084/jem.156.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science. 1983 May 6;220(4597):568–575. doi: 10.1126/science.6301011. [DOI] [PubMed] [Google Scholar]
- Weichman B. M., Hostelley L. S., Bostick S. P., Muccitelli R. M., Krell R. D., Gleason J. G. Regulation of the synthesis and release of slow-reacting substance of anaphylaxis from sensitized monkey lung. J Pharmacol Exp Ther. 1982 May;221(2):295–302. [PubMed] [Google Scholar]
- Weller P. F., Lee C. W., Foster D. W., Corey E. J., Austen K. F., Lewis R. A. Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: predominant production of leukotriene C4. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7626–7630. doi: 10.1073/pnas.80.24.7626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziltener H. J., Chavaillaz P. A., Jörg A. Leukotriene formation by eosinophil leukocytes. Analysis with ion-pair high pressure liquid chromatography and effect of the respiratory burst. Hoppe Seylers Z Physiol Chem. 1983 Aug;364(8):1029–1037. doi: 10.1515/bchm2.1983.364.2.1029. [DOI] [PubMed] [Google Scholar]
