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Platelet activation by endogenous 5-hydroxytryptamine and histamine released by mast cell degranulation with compound 48/80 in the rat

  • Platelets and Thrombosis
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Abstract

The intravenous injection of the mast cell degranulator C 48/80 (1 mg/kg) in rats did not produce thrombocytopenia nor circulating platelet aggregates but sensitized the platelets to aggregate upon turbulence challenge. Such turbulence-induced platelet aggregation was not accompanied by formation of thromboxane B2. Electron microscopy revealed absence of platelet degranulation. Turbulence-induced platelet aggregation was completely prevented by pre-treatment of the rats with cyproheptadine, dipyridamole and VK 774, partially with ketanserin (5HT2-receptor antagonist), but not with methysergide (anti-serotonergic drug), pyrilamine (antihistaminic drug), suprofen, aspirin (cyclo-oxygenase inhibitors), phentolamine, propranolol, flunarizine, lidoflazine, oxycoumarin or Trasylol®. Combined treatment with the anti-histaminic drug pyrilamine and the 5HT2-receptor antagonist ketanserin resulted in a dose-related inhibition for ketanserin of the turbulence-induced platelet aggregation. These experiments point to an interaction between histamine and 5-hydroxytryptamine in the platelet activation by mast cell released mediators.

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Authors and Affiliations

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

    F. De Clerck, Y. Somers, L. Van Gorp & B. Xhonneux

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  1. F. De Clerck
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  2. Y. Somers
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  3. L. Van Gorp
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  4. B. Xhonneux
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De Clerck, F., Somers, Y., Van Gorp, L. et al. Platelet activation by endogenous 5-hydroxytryptamine and histamine released by mast cell degranulation with compound 48/80 in the rat. Agents and Actions 13, 81–87 (1983). https://doi.org/10.1007/BF01994287

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