The involvement of 5-HT2-receptor sites in the activation of cat platelets

5-Hydroxytryptamine (5-HT) induces a concentration-dependent aggregation/release of/by cat platelets (Km = 6.2 x 10(-7) M); this activation is inhibited (Ki = 5.24 x 10(-9) M) or reversed by ketanserin, a selective 5-HT2 receptor antagonist. Comparison of the inhibition of specific [3H] ketanserin binding to cat platelet membranes and rat pre-frontal cortex membranes with that of 5-HT-induced aggregation of cat platelets obtained with various drugs, displaying various receptor binding profiles, reveals a highly significant correlation between the ligand binding and the physiological response (Spearman correlation coefficient r = 0.92 and r = 0.91 respectively, p less than 0.0001; n = 14); inhibition of platelet activation by 5-HT and of uptake of 5-HT are not correlated. Secondary aggregation induced by ADP as well as collagen-induced aggregation are inhibited by the 5-HT receptor antagonists suggesting a primary role of 5-HT in the secondary platelet recruitment subsequent to a release reaction. This study demonstrates a functional role for the 5-HT2 receptors in the primary activation of the platelets by 5-HT and in the secondary aggregation induced by other agonists, especially in platelets superreactive to 5-HT2 receptor activation.