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Effects of ketanserin, a selective 5-HT2 serotonergic antagonist, on the secondary recruitment of human plateletsin vitro

  • Platelets and Thrombosis
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Abstract

Ketanserin, a selective 5-HT2 serotonergic receptor antagonist, reducesin vitro the release-associated human platelet aggregation induced by threshold concentrations of collagen and curtails the second wave of aggregation/release induced by critical concentrations of ADP in particular and, to a lesser extent, of 1-epinephrine. Its inhibitory effect on the second waves becomes more pronounced when the reaction is already attenuated by moderate cyclo-oxygenase inhibition with esculetin, by yohimbine or by propranolol. The first wave of aggregation induced by ADP or 1-epinephrine is not affected.

Such an inhibition of secondary platelet recruitment by ketanserinin vitro may be due to an inhibition of the 5-HT2 receptor-mediated amplifying effects of platelet-released 5-HT or to a non-specific interference with the platelet membrane, reducing the release of mediators from the platelets.

Reduction of the increased plasma BTG levels in patients after ketanserin may result from such release-inhibiting mechanisms.

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References

  1. J.E. Leysen, F. Awouters, L. Kenis, P.M. Laduron, L. Van den Berk andP.A.J. Janssen,Receptor binding profile of R 41, 468, a novel antagonist at 5-HT 2 receptors, Life Sci.28, 1015–1022 (1981).

    PubMed  Google Scholar 

  2. F. De Clerck, J.L. David andP.A.J. Janssen,Inhibition of 5-hydroxytryptamine-induced and-amplified human platelet aggregation by ketanserin (R 41 468), a selective 5-HT 2-receptor antagonist, Agents and Actions12, 388–397 (1982).

    PubMed  Google Scholar 

  3. F. De Clerck, B. Xhonneux, J. Leysen andP.A.J. Janssen,The involvement of 5-HT 2-receptor sites in the activation of cat platelets, Thromb. Res.33, 303–321 (1984).

    Google Scholar 

  4. F. De Clerck andA.G. Herman,5-Hydroxytryptamine and platelet aggregation, Fedn. Proc.42, 228–232 (1983).

    Google Scholar 

  5. D.C.B. Mills, I.A. Robb andG.C.K. Roberts,The release of nucleotides, 5-hydroxytryptamine and enzymes from human blood platelets during aggregation, J. Physiol.195, 715–729 (1968).

    PubMed  Google Scholar 

  6. H. Holmsen, A.C. Østwald andH.J. Day,Behaviour of endogenous and newly absorbed serotonin in the platelet release reaction, Biochem. Pharmac.22, 2599–2608 (1973).

    Google Scholar 

  7. H. Holmsen,Prostaglandin endoperoxide-thromboxane synthesis and dense granule secretion as positive feedback loops in the propagation of platelet responses during ‘the basic platelet reaction’, Thromb. Haemostas. (Stuttg.)38, 1030–1041 (1977).

    Google Scholar 

  8. L.C. Best, T.K. Holland, P.B.B. Jones andR.G.G. Russell,The interrelationship between thromboxane biosynthesis, aggregation and 5-hydroxytryptamine secretion in human platelets in vitro, Thromb. Haemostas.43, 38–40 (1980).

    Google Scholar 

  9. B.B. Vargaftig, M. Chignard, J.P. Le Couedic andJ. Benveniste,One two, three or more pathways for platelet aggregation, Acta med. scand. (Suppl.)642, 23–29 (1980).

    Google Scholar 

  10. B.B. Vargaftig, M. Chignard andJ. Beneviste,Present concepts on the mechanisms of platelet aggregation, Biochem. Pharmac.30, 263–271 (1981).

    Google Scholar 

  11. H. Da Prada, J.G. Richards andR. Kettler, Amine storage organelles in platelets. InPlatelets in Biology and Pathology—2, pp. 107–145 (Ed.J.L. Gordon). Elsevier-North Holland Biomedical Press, Amsterdam 1981.

    Google Scholar 

  12. F. De Clerck, J. Vermylen andR. Reneman,Effects of suprofen, an inhibitor of prostaglandin biosynthesis on platelet function, plasma coagulation and fibrinolysis. I. In vitroexperiments, Arch. int. Pharmacodyn. Ther.216, 263–279 (1975).

    PubMed  Google Scholar 

  13. R.D. Feinman, J. Lubowsky, I. Charo andM.P. Zabiwski,The lumi-aggregometer: a new instrument for simultaneous measurement of secretion and aggregation by platelets, J. Lab. clin. Med.90, 125–129 (1977).

    PubMed  Google Scholar 

  14. A.H. Drummond andJ.L. Gordon,Rapid, sensitive microassay for platelet 5-HT, Thromb. Diath. haemorrh.31, 366–367 (1974).

    PubMed  Google Scholar 

  15. F. De Clerck andJ.M. Van Nueten,Platelet-mediated vascular contractions: inhibition of the serotonergic component by ketanserin, Thromb. Res.27, 713–727 (1982).

    PubMed  Google Scholar 

  16. H.R. Baumgartner andG.V.R. Born,Effect of 5-hydroxytryptamine on platelet aggregation, Nature218, 137–141 (1968).

    PubMed  Google Scholar 

  17. F. De Clerck, B. Xhonneux, J. Leysen andP.A.J. Janssen,Evidence for functional 5-HT 2 receptor sites on human blood platelets, Biochem. Pharmac.33, 2807–2811 (1984).

    Google Scholar 

  18. D.P. Thomas,The role of platelet catecholamines in the aggregation of platelets by collagen and thrombin, Exp. Biol. Med.3, 129–134 (1968).

    Google Scholar 

  19. P. Kubisz andJ. Caen,Interaction of alpha and beta receptor blocking agents with platelet release and availability reaction induced by ADP, adrenaline and collagen, Path. Biol.20 (Suppl.) 34–40 (1972).

    Google Scholar 

  20. C.E. Dutilh, E. Haddeman, J.A. Don andF. Tenhoor,The role of arachidonate lipoxygenase and fatty acids during irreversible blood platelet aggregation in vitro, Prostaglandines and Medicine6, 111–126 (1981).

    Google Scholar 

  21. J. Bevan andS. Heptinstall,Effects of ketanserin and mepyramine on platelet aggregation and on the uptake of 5-hydroxytryptamine into platelets, Thromb. Res.30, 415–423 (1983).

    PubMed  Google Scholar 

  22. I.E. Charo, R.D. Feinman andT.C. Detweiler,Interrelations of platelet aggregation and secretion, J. clin. Invest.60, 866–873 (1977).

    PubMed  Google Scholar 

  23. R.J. Haslam,Role of adenosine diphosphate in the aggregation of human blood platelets by thrombin and by fatty acids, Nature202, 765–768 (1964).

    PubMed  Google Scholar 

  24. A. Willis andD.C. Kuhn,A new potential mediator of arterial thrombosis whose biosynthesis is inhibited by aspirin, Prostaglandins4, 127–139 (1970).

    Google Scholar 

  25. J.B. Smith, C. Ingerman, J.J. Kocsis andM.S. Silver,Formation of an intermediate in prostaglandin biosynthesis and its association with the release reaction, J. clin. Invest.53, 1468–1472 (1974).

    PubMed  Google Scholar 

  26. M. Packham, M.A. Gullione, J.P. Greenberg, R.L. Kinbough-Rathbone andJ.F. Mustard,Release of 14 C-serotonin during initial platelet changes induced by thrombin, collagen or A 23187, Blood50, 915–926 (1977).

    PubMed  Google Scholar 

  27. M.F. Gimeno, M.A. Shattner, E. Borda, A.L. Gimeno andM.A. Laziari,Lipoxygenase inhibitors alter aggregation and adhesiveness of human blood platelets from aspirin-treated patients, Prostaglandins Leukotrienes Med.11, 109–119 (1983).

    Google Scholar 

  28. S. Heptinstall, J. Bevan, S.R. Cockbill, S.P. Hanley andM.J. Parry,Effects of a selective inhibitor of thromboxane synthetase on human blood platelet behaviour, Thromb. Res.20, 219–230 (1980).

    PubMed  Google Scholar 

  29. J. Vermylen, L.O. Carreras, J. Van Schaeren, G. De Freyn, S.J. Machen andM. Verstraete,Thromboxane synthetase inhibition as antithrombotic strategy, Lanceti, 1073–1075 (1981).

    Google Scholar 

  30. F. De Clerck andJ.L. David, Effects of antimigraine drugs on platelet behaviour. InThe Pharmacological Basis of Migraine Therapy, pp. 81–98 (Eds.W.K. Amery, J.M. Van Nueten andA. Wauquier). Pitman Publishing Co., Ltd., London 1984.

    Google Scholar 

  31. D.C.D. Mills andG.C.K. Roberts,Membraneactive drugs and the aggregation of human platelets, Nature213, 35–38 (1967).

    Google Scholar 

  32. A. Amery, R. Fagard, R. Fiocchi, P. Lijnen, J. Staessen andJ. Vermylen,Antihypertensive action and serotonin-induced platelet aggregation during longterm ketanserin treatment in hypertensive patients, J. Cardiovasc. Pharmac.6, 182–185 (1984).

    Google Scholar 

  33. R. Zannad, J.P. Pointel, J.R. Stoltz andJ.M. Golgenkrantz,Effects of ketanserin on hemorheology and platelet function: in vivostudies, IXth European Congress of Cardiology, Dusseldorf, July 8–12, 1984 (Abstract).

  34. J.C. Demoulin, M. Bertholet, D. Soumagne, J.L. David andH.E. Kulbertus,5-HT 2-receptor blockade in the treatment of heart failure, Lanceti, 1186–1188 (1981).

    Google Scholar 

  35. J. De Cree, J. Leempoels, B. Demoen, V. Roels andH. Verhaegen,The effect of ketanserin, a 5-HT 2-antagonist on 5-hydroxytryptamine-induced irreversible platelet aggregation in patients with cardiovascular diseases, Agents and Actions16, 313–317 (1985).

    PubMed  Google Scholar 

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  1. Laboratory of Haematology, Department of Life Sciences, Janssen Pharmaceutica Research Laboratories, B-2340, Beerse, Belgium

    Fred De Clerck & Benoit Xhonneux

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  1. Fred De Clerck
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  2. Benoit Xhonneux
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De Clerck, F., Xhonneux, B. Effects of ketanserin, a selective 5-HT2 serotonergic antagonist, on the secondary recruitment of human plateletsin vitro . Agents and Actions 17, 515–526 (1986). https://doi.org/10.1007/BF01965524

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