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.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002415:Cats; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007650:Ketanserin; D007700:Kinetics; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*
D010880:Piperidines; D011985:Receptors, Serotonin; D012701:Serotonin; D000244:Adenosine Diphosphate; D003094:Collagen; D007650:Ketanserin