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PMID: 41240 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Leukotriene C: a slow-reacting substance from murine mastocytoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 76 ·No. 9 ·1979-09-00 ·Pages 4275-9

Murphy RC, Hammarström S, Samuelsson B

Abstract

Murine mastocytoma cells treated with calcium ionophore A23187 produced a slow-reacting substance (SRS) that caused guinea pig ileum to contract. The response was reversed by the SRS antagonist FPL 55712. On the basis of isotope incorporation experiments, spectroscopy, and chemical degradations, the SRS was identified as a cysteine-containing derivative of 5-hydroxy-7,9,11,14-icosatetraenoic acid. This amino acid was attached in thioether linkage at C-6. The SRS is structurally related to previously identified epoxy and dihydroxy metabolites of arachidonic acid in leukocytes. A common feature is the presence of a conjugated triene, and the name "leukotriene" has been introduced to designate these compounds. Leukotriene A (5,6-epoxy-7,9,11,14-icosatetraenoic acid) is an intermediate in the formation of leukotriene B (5,12-dihydroxy-6,8,10,14-icosatetraenoic acid) and is proposed to be a precursor also of leukotriene C, which is the SRS identified here.

Keywords
Abortifacient Agents--analysis Abortion Drug Induced Abortion Induced Clinical Research Family Planning Fertility Control Postconception In Vitro Research Methodology
MeSH Terms
Animals Arachidonic Acids/analysis Autacoids/analysis,biosynthesis Calcimycin/pharmacology Cells, Cultured Cysteine/analogs & derivatives,analysis Ionophores/pharmacology Mast-Cell Sarcoma/analysis Mice SRS-A/isolation & purification Sarcoma, Experimental/analysis
Chemicals
Arachidonic Acids Autacoids Ionophores SRS-A Calcimycin Cysteine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Murphy R C
Hammarström S
Samuelsson B
Other Abstracts
eng

This paper reports that the ionophore-induced slow-reacting substance (SRS) from mast cell tumor leukocytes is a member of a group of compounds called leukotrienes. Briefly, murine mastocytoma cells treated with calcium ionophore produced a SRS that caused guinea pig ileum to contract. This response could be reversed by an SRS antagonist, FPL 55712. Based on osotope incorporation experiments, spectrophotometry, and chemical degradation analyses, the SRS was identified. It is a cysteine-containing derivative of 5-hydroxy-7,9,11,14-icosatetraenoic acid, which was attached in a thioether linkage at C-6. The SRS was structurally related to previously identified epoxy and dihydroxy metabolites of arachidonic acid in leukocytes. The leukotrienes have the common feature of the presence of a conjugated triene. Leukotriene A is an intermediate in the formation of leukotriene B, and is proposed to be the precursor also of leukotriene C, the SRS chemically identified in this paper.

References (24)
24 references, click to expand
  1. The release of 35-S-labelled material and SRS-A from immunologically challenged guinea-pig lungs.
    J Physiol. 1975 May;247(1):37P-38P PMID: 1138065
  2. Liberation of histamine and formation of lysocithin-like substances by cobra venom.
    J Physiol. 1938 Nov 14;94(2):187-226 PMID: 16995038
  3. On the structure of slow reacting substance of anaphylaxis: evidence of biosynthesis from arachidonic acid.
    Prostaglandins. 1977 Jul;14(1):21-38 PMID: 19813
  4. Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells.
    Proc Natl Acad Sci U S A. 1977 Oct;74(10):4577-81 PMID: 22078
  5. Arachidonic acid metabolism in polymorphonuclear leukocytes: unstable intermediate in formation of dihydroxy acids.
    Proc Natl Acad Sci U S A. 1979 Jul;76(7):3213-7 PMID: 290996
  6. Stimulated production of slow reacting substances by mercaptans from ionophore A 23187-induced mononuclear cells: mercaptan structure-activity studies.
    Life Sci. 1978 Nov 20;23(21):2119-26 PMID: 31540
  7. Release of slow reacting substance (SRS) from rat basophilic leukemia (RBL-1) cells.
    J Immunol. 1977 Aug;119(2):618-22 PMID: 328779
  8. Ionophore A 23187-induced production of slow reacting substance of anaphylaxis (SRS-A) by rat peritoneal cells in vitro: evidence for production by mononuclear cells.
    J Immunol. 1978 Mar;120(3):998-1005 PMID: 344800
  9. Homeostasis of effector systems which can also be recruited for immunologic reactions.
    J Immunol. 1978 Sep;121(3):793-805 PMID: 357653
  10. Effects of modulators of arachidonic acid metabolism on the synthesis and release of slow-reacting substance of anaphylaxis.
    Br J Pharmacol. 1979 Jan;65(1):35-41 PMID: 367476
  11. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187.
    Proc Natl Acad Sci U S A. 1979 May;76(5):2148-52 PMID: 377292
  12. Purification and properties of the slow reacting substance formed in the cat paw perfused with compound 48-80.
    Acta Physiol Scand. 1971 Jul;82(3):358-74 PMID: 4108403
  13. Slow reacting substance of anaphylaxis.
    Adv Immunol. 1969;10:105-44 PMID: 4188319
  14. Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid.
    J Biol Chem. 1979 Apr 25;254(8):2643-6 PMID: 429307
  15. The physicochemical characteristics and purification of slow-reacting substance of anaphylaxis.
    J Immunol. 1973 Mar;110(3):760-70 PMID: 4347478
  16. Inactivation of slow reacting substance of anaphylaxins (SRS-A) by arylsulfatases.
    J Immunol. 1974 Jul;113(1):316-22 PMID: 4832311
  17. Steric analysis of hydroperoxides formed by lipoxygenase oxygenation of linoleic acid.
    Anal Biochem. 1971 Oct;43(2):515-26 PMID: 5168775
  18. The effect of thiols on the immunologic release of slow reacting substance of anaphylaxis. II. Other in vitro and in vivo models.
    J Immunol. 1976 Feb;116(2):392-7 PMID: 55439
  19. On the specificity of the oxygenation of unsaturated fatty acids catalyzed by soybean lipoxidase.
    J Biol Chem. 1967 Nov 25;242(22):5329-35 PMID: 6070850
  20. Slow-reacting substance of anaphylaxis: purification and characterisation.
    FEBS Lett. 1978 Mar 15;87(2):203-6 PMID: 631337
  21. Release of mediators of anaphylaxis: inhibition of prostaglandin synthesis and the modification of release of slow reacting substance of anaphylaxis and histamine.
    Br J Pharmacol. 1978 Jan;62(1):61-6 PMID: 74266
  22. Slow reacting substances: comparison of some properties of human lung SRS-A and two distinct fractions from ionophore-induced rat mononuclear cell SRS.
    J Immunol. 1979 Jan;122(1):160-5 PMID: 762414
  23. Prostaglandins and slow-reacting substance.
    J Allergy Clin Immunol. 1979 Jan;63(1):1-14 PMID: 82564
  24. Separation of slow reacting substance of anaphylaxis (SRS-A) from human lung into four biologically active fractions.
    J Immunol. 1976 Sep;117(3):1039-44 PMID: 8568
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.76.9.4275
Published
1979-09-00
Pages
4275-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC411556
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.76.9.4275 PMC Full Text View journal details
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