Home LiteratureArticle Details
PMID: 6961445 Published · ppublish English Journal Article

Cytochalasins inhibit arachidonic acid metabolism in thrombin-stimulated platelets.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 79 ·No. 24 ·1982-12-00 ·Pages 7709-13

Siess W, Lapetina EG, Cuatrecasas P

Abstract

Low concentrations (0.5-1 microM) of cytochalasins inhibit the thrombin-stimulated polymerization of monomeric actin to filamentous actin in platelets. Similar concentrations of cytochalasin B inhibit the formation and metabolism of arachidonic acid in horse platelets stimulated by low concentrations of thrombin (0.1-0.5 unit/ml). However, the release of serotonin is not inhibited by cytochalasin B. Cytochalasins B and D (0.5-1 microM) markedly reduce, in thrombin-stimulated human or horse platelets, the metabolism of the liberated arachidonic acid by cyclooxygenase activity to thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid and the conversion of arachidonic acid by lipoxygenase activity to 12-hydroxy-5,8,10,14-icosatetraenoic acid. The generation of arachidonic acid from platelet phospholipids and the formation of phosphatidic acid are much less affected by cytochalasin B or D. Cytochalasins do not directly inhibit platelet cyclooxygenase, lipoxygenase, phospholipase A2, or phosphatidyl-inositol-specific phospholipase C. In addition, the metabolism of exogenously added arachidonic acid by intact platelets is not inhibited by cytochalasins B and D. The results indicate that polymerization of actin in platelets stimulated by thrombin may be required for the effective metabolism of arachidonic acid released from platelet phospholipids.

MeSH Terms
Actins/metabolism Animals Arachidonic Acids/metabolism Blood Platelets/drug effects,metabolism Cytochalasins/pharmacology Cytoskeleton/drug effects Horses Phospholipases/metabolism Thrombin/metabolism
Chemicals
Actins Arachidonic Acids Cytochalasins Phospholipases Thrombin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Siess W
Lapetina E G
Cuatrecasas P
References (30)
30 references, click to expand
  1. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  2. Inhibition and reversal of platelet activation by cytochalasin B or colcemid.
    Nature. 1973 Aug 3;244(5414):288-9 PMID: 4583103
  3. Inhibition of platelet adherence to a collagen-coated surface by agents that inhibit platelet shape change and clot retraction.
    J Lab Clin Med. 1974 Oct;84(4):483-93 PMID: 4370106
  4. Cytochalasin B, the blood platelet release reaction and cyclic GMP.
    Nature. 1975 Feb 6;253(5491):455-7 PMID: 163012
  5. Metabolism of [14C]arachidonic acid by human platelets.
    Biochim Biophys Acta. 1976 Feb 23;424(2):303-14 PMID: 1252495
  6. Production of diglyceride from phosphatidylinositol in activated human platelets.
    J Clin Invest. 1979 Apr;63(4):580-7 PMID: 220279
  7. Stimulation of phosphatidic acid production in platelets precedes the formation of arachidonate and parallels the release of serotonin.
    Biochim Biophys Acta. 1979 May 25;573(2):394-402 PMID: 375988
  8. Substoichiometric concentrations of cytochalasin D inhibit actin polymerization. Additional evidence for an F-actin treadmill.
    J Biol Chem. 1979 Oct 25;254(20):9982-5 PMID: 489616
  9. Aspirin-like drugs interfere with arachidonate metabolism by inhibition of the 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway.
    Proc Natl Acad Sci U S A. 1979 Aug;76(8):3774-8 PMID: 115007
  10. Cytochalasins block actin filament elongation by binding to high affinity sites associated with F-actin.
    J Biol Chem. 1980 Feb 10;255(3):835-8 PMID: 7356663
  11. Cytochalasin inhibits the rate of elongation of actin filament fragments.
    J Cell Biol. 1979 Dec;83(3):657-62 PMID: 574873
  12. Reorganization of actin in platelets stimulated by thrombin as measured by the DNase I inhibition assay.
    Proc Natl Acad Sci U S A. 1979 Dec;76(12):6376-80 PMID: 118466
  13. Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover.
    J Biol Chem. 1980 Mar 25;255(6):2273-6 PMID: 7358670
  14. Differential effects of cytochalasin B on platelet release, aggregation and contractility: evidence against a contractile mechanism for the release of platelet granular contents.
    Thromb Haemost. 1980 Feb 29;42(5):1483-9 PMID: 6892735
  15. Mechanism of action of cytochalasin B on actin.
    Cell. 1980 Jun;20(2):329-41 PMID: 6893016
  16. Relationship of ADP-induced fibrinogen binding to platelet shape change and aggregation elucidated by use of colchicine and cytochalasin B.
    Thromb Haemost. 1980 Feb 29;43(1):58-60 PMID: 7404479
  17. Cytoskeleton of human platelets at rest and after spreading.
    J Cell Biol. 1980 Sep;86(3):795-802 PMID: 6157694
  18. Phospholipase A2 and phospholipase C activities of platelets. Differential substrate specificity, Ca2+ requirement, pH dependence, and cellular localization.
    J Biol Chem. 1980 Nov 10;255(21):10227-31 PMID: 7430120
  19. Inhibitors of ADP-induced platelet aggregation prevent fibrinogen binding to rabbit platelets and cause rapid deaggregation and dissociation of bound fibrinogen.
    J Lab Clin Med. 1981 May;97(5):680-8 PMID: 6783712
  20. The initial action of thrombin on platelets. Conversion of phosphatidylinositol to phosphatidic acid preceding the production of arachidonic acid.
    J Biol Chem. 1981 May 25;256(10):5037-40 PMID: 6785276
  21. Platelet activation and microfilament bundling.
    J Cell Biol. 1981 Apr;89(1):146-51 PMID: 7194875
  22. Changes in the cytoskeletal structure of human platelets following thrombin activation.
    J Biol Chem. 1981 Jul 10;256(13):6927-32 PMID: 6894599
  23. The state of actin in activated human platelets.
    Eur J Biochem. 1981 May 15;116(2):293-6 PMID: 6265215
  24. The phosphatidylinositol cycle and the regulation of arachidonic acid production.
    Nature. 1981 Jul 23;292(5821):367-9 PMID: 6265791
  25. Inhibition of actin polymerization in blood platelets by cytochalasins.
    Nature. 1981 Aug 13;292(5824):650-2 PMID: 6894786
  26. Cytochalasin D inhibits actin polymerization and induces depolymerization of actin filaments formed during platelet shape change.
    Nature. 1981 Sep 24;293(5830):302-5 PMID: 7196996
  27. Action of cytochalasin D on cytoskeletal networks.
    J Cell Biol. 1982 Jan;92(1):79-91 PMID: 7199055
  28. Formation of lysophosphatidylinositol in platelets stimulated with thrombin or ionophore A23187.
    J Biol Chem. 1982 May 10;257(9):5196-200 PMID: 6802848
  29. Cytochalasin D and platelet gelsolin accelerate actin polymer formation. A model for regulation of the extent of actin polymer formation in vivo.
    Biochemistry. 1982 Jun 22;21(13):3207-14 PMID: 6285961
  30. The use of prostacyclin in the separation from plasma and washing of human platelets.
    Prostaglandins. 1982 Jun;23(6):929-45 PMID: 6812168
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.79.24.7709
Published
1982-12-00
Pages
7709-13
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC347417
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.79.24.7709 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2