Manipulation of Pro- and Antiaggregating Prostaglandins: New Antithrombotic Strategies

  • H. Deckmyn
  • P. Gresele
  • J. Arnout
  • J. Vermylen
Part of the NATO ASI Series book series (NSSA, volume 95)


A number of cyclooxygenase products have potent actions on platelets: thromboxane A2 (TXA2), the cyclic endoperoxides Prostaglandins G2 and H2 (PG2’H2) and to some extent PGE2 are proaggregatory, whereas prostacyciin (PGI2) and PGD2 inhibi platelet activation. Attempts to change the balance in favour of the antiaggregatory PG’s therefore could be of benefit in thrombotic situations, and can be done at different levels: selective in- hibition of platelet cyclooxygenase, stimulation of the PGI2 synthesis, inhibition of TXA2 synthesis or blockage of the TXA2 receptor.


Thromboxane Synthetase Thromboxane Receptor Platelet Cyclooxygenase Antithrombotic Strategy PGI2 Synthesis 
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  1. 1.
    P. Patrignani, P. Filabozzi, and C. Patrono, Low-dose aspirin is a selective inhibitor of platelet cyclo-oxygenase activity in healthy subjects, in: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research, Vol. 11”, B. Samuelsson, R. Paoletti, and P. Ramwell, eds., Raven Press, New York, p. 259 (1983).Google Scholar
  2. 2.
    G. Remuzzi, M. Livio, A.E. Cavenaghi, D. Marchesi, G. Mecca, M.B. Donati, and G. de Gaetano, Unbalanced prostaglandin synthesis and plasma factors in uraemic bleeding. A hypothesis, Thromb. Res. 13: 531 (1978).Google Scholar
  3. 3.
    J. Vermylen, D.A.F. Chamone, and M. Verstraete, Stimulation of prostacyclin release from vessel wall by Bay g 6575, an antithrombotic compound, Lancet i: 518 (1979).Google Scholar
  4. 4.
    H. Deckmyn, C. Zoja, J. Arnout, A. Todisco, F. Vanden Bulcke, L. D’Hondt, N. Hendrickx, P. Gresele, and J. Vermylen, Partial isolation and function of the prostacyclin regulating plasma factor. (submitted).Google Scholar
  5. 5.
    J.R. Babson and D.J. Reed, Inactivation of glutathione reductase by 2-chloroethyl nitrosourea-derived isocyanates, Biochem. Biophys. Res. 83: 754 (1978).CrossRefGoogle Scholar
  6. 6.
    H. Deckmyn, P. Gresele, J. Arnout, A. Todisco, and J. Vermylen, Prolonging prostacyclin production by nafazatrom and dipyridamole, Lancet ii: 410 (1984).Google Scholar
  7. 7.
    H. Deckmyn, E. Van Houtte, M. Verstraete, and J. Vermylen, Manipulation of the local thromboxane and prostacyclin balance in vivo by the antithrombotic compounds dazoxiben, acetylsalicylic acid and nafazatrom, Biochem. Pharmacol. 32: 2757 (1983).Google Scholar
  8. 8.
    J. Vermylen, G. Defreyn, L.O. Carreras, S.J. Machin, J. Van Schaeren, and M. Verstraete, Thromboxane synthetase inhibition as antithrombotic strategy, Lancet i: 1073 (1981).Google Scholar
  9. 9.
    S. Heptinstall, J. Bevan, S.R. Cockbill, S.P. Hanley, and M.J. Parry, Effects of a selective inhibitor of thromboxane synthetase on human blood platelet behaviour, Thromb. Res. 20: 219 (1980).Google Scholar
  10. 10.
    T. Watanabe, S. Narumiya, T. Shimizu, and 0. Hayaishi, Characterization of the biosynthetic pathway of prostaglandin D2 in human platelet-rich plasma, J. Biol. Chem. 257: 14843 (1982).Google Scholar
  11. 11.
    M. Hamberg and B.B. Fredholm, Isomerization of prostaglandin H2 into prostaglandin D2, Biochim. Biophys. Acta 431: 189 (1976).Google Scholar
  12. 12.
    P. Gresele, H. Deckmyn, E. Huybrechts, and J. Vermylen, Serum albumin enhances the impairment of platelet aggregation with thromboxane synthase inhibition by increasing the formation of prostaglandin D2, Biochem. Pharmacol. 33: 2083 (1984).Google Scholar
  13. 13.
    G. Defreyn, H. Deckmyn, and J. Vermylen, A thromboxane synthetase inhibitor reorients endoperoxide metabolism in whole blood towards prostacyclin and prostaglandin E2, Thromb. Res. 26: 389 (1982).Google Scholar
  14. 14.
    P. Gresele, H. Deckmyn, J. Arnout, J. Lemmens, W. Janssens, and J. Vermylen, BM 13.177, a selective blocker of platelet and vessel wall thromboxane receptors is effective in man, Lancet i: 991 (1984).Google Scholar
  15. 15.
    P. Gresele, E. Van Houtte, J. Arnout, H. Deckmyn, and J. Vermylen, Thromboxane synthase inhibition combined with thromboxane receptor blockade: a step forward in anti-thrombotic strategy?, Thromb. Haemost. (in press).Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • H. Deckmyn
    • 1
  • P. Gresele
    • 1
  • J. Arnout
    • 1
  • J. Vermylen
    • 1
  1. 1.Centre for Thrombosis and Vascular ResearchDepartment of Medical Research K.U. LeuvenLeuvenBelgium

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