Platelet-vessel wall interactions in hemostasis: implication of 5-hydroxytryptamine.

5-Hydroxytryptamine (5-HT) is implicated in the platelet-vessel wall interactions during hemostasis. Indeed, the tail bleeding time and the initial blood loss in rats are significantly increased by platelet amine depletion with reserpine/parachlorophenylalanine, by the specific 5-HT2 receptor antagonists ketanserin, R 55 667 and R 56 433 and by the ergot derivatives metergoline and methysergide. In the dose range affecting hemostasis, the serotonergic receptor antagonists also inhibit the 5-HT-amplified aggregation of ADP-sensitized platelets in rat whole blood. Bleeding times are also prolonged by alpha 1-adrenergic receptor antagonism with prazosin or phentolamine, by specific thromboxane A2-synthetase inhibition with R 59 655 or dazoxiben, and by anticoagulant treatment. The latter three mechanisms of action are not explanatory for the effect of the tested serotonergic antagonists, since bleeding times are prolonged by specific 5-HT2 receptor antagonists without an effect on alpha-adrenergic receptors, on platelet prostaglandin biosynthesis or on coagulation and fibrinolysis. The present study shows the interplay between the platelet-derived mediators 5-HT and TXA2 at the level of the platelet or the blood vessel to be of major importance in the platelet-vessel wall interactions during hemostasis.