Influence of a selective 5HT1-receptor agonist GR43175 on platelet responsiveness

The possible interaction of sumatriptan, a selective 5HT(1)-receptor agonist, with platelet responsiveness has been investigated. Stimulation of platelet rich plasma with sumatriptan (1-100 mu M) did not induce shape change, aggregation or modification of intraplatelet cytosolic calcium levels, Total inhibition of aggregation induced by 20 mu M 5HT was observed in platelets preincubated for 20 min with 100 mu M sumatriptan. In the same model, platelet stimulation with 4 mu M adenosine 5'-diphosphate (ADP), concentration known to induce an irreversible single-phase curve, determined a decrease of aggregatory response. Concentrations from 1 mu M to 50 mu M of sumatriptan did not influence the aggregatory response induced by 5HT and ADP. These effects appear not to be determined by modifications of platelet calcium homeostasis. The possibility to modulate platelet responsiveness by sumatriptan offers a further approach for evaluating the probable link between platelet behaviour and pathophysiology of migraine.