Platelet activation by endogenous 5-hydroxytryptamine and histamine released by mast cell degranulation with compound 48/80 in the rat.
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 (antiserotonergic 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.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000187:drug effects; D006632:Histamine / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013921:Thrombocytopenia / Q000139:chemically induced; D013929:Thromboxane B2 / Q000096:biosynthesis; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D013929:Thromboxane B2; D006632:Histamine