The role of serotonin in thrombogenesis.
Serotonin, a weak activator on its own, elicits strong platelet reactions (aggregation, arachidonate metabolization, release reaction) through amplification. Such amplification operates via 5-HT2-serotonergic receptors which are linked to the turnover of polyphosphoinositides and increases of intracellular [Ca2+]i concentrations as signal transducing systems. In experimental animals, selective blockade of 5-HT2-serotonergic receptors eliminates arterial thrombus formation over sites of endothelial injury in stenosed canine coronaries; in combination with a manipulation of TXA2, it prevents coronary thrombotic reocclusion after fibrinolysis with rt-PA, and inhibits drastic platelet activation, elicited by injections of collagen in vivo. These observations suggest that serotonergic amplification substantially contributes to the aggregation of platelets in damaged vessels and offers perspectives for an improved antithrombotic approach.
De Clerck
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Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D005342:Fibrinolysis / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000378:metabolism
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D013928:Thromboxane A2; D007650:Ketanserin; D002118:Calcium