The role of serotonin in haemostasis

Summary

Serotonin is transported by platelets and released upon activation. This induces constriction of injured blood vessels and enhances platelet aggregation to minimize blood loss. Consequently, serotonin receptor antagonists have been tested for their anti-ischemic potency in atherothrombotic disease. Unfortunately, the results have been contradictory. Recent murine studies found that activation of the platelet serotonin receptor induces shedding of important adhesion molecules. As a consequence, platelets lose their ability to contribute to thrombus formation and may be cleared from the circulation. Serotonin effects on platelets are not only mediated by receptor binding but also by covalently binding effector proteins (serotonylation) in the platelet cytoplasm and on the platelet surface. In conclusion, the effects of serotonin on haemo -stasis are complex and new antithrombotic strategies have to account for this complexity.

Zusammenfassung

Serotonin wird von Blutplättchen transportiert und bei Aktivierung freigesetzt. Verletzte Blutgefäße kontrahieren sich dadurch und die Plättchenaggregation wird verstärkt um Blutverlust zu minimieren. Serotoninrezeptor-Antagonisten wurden deshalb auf ihre antiischämische Potenz bei atherothrombotischen Erkrankungen untersucht. Die Ergebnisse bisheriger Studien waren jedoch widersprüchlich. Neuere Mausversuche zeigen, dass die isolierte Aktivierung des Plättchen-Serotoninrezeptors den Verlust von Adhäsionsmolekülen auf der Plättchenoberfläche bewirkt. Serotoninstimulierte Plättchen verlieren so ihre Fähigkeit, zur Bildung arterieller Thromben beizutragen und werden aus dem Körper eliminiert. Komplizierend werden Serotonineffekte nicht nur über Oberflächenrezeptoren sondern auch über die Regulierung des Serotonintransports in die Plättchen und die kovalente Bindung an Effektorproteine (Serotonylierung) im Plättcheninneren und auf der Plättchenoberfläche vermittelt. Die Wirkungen von Serotonin auf die Hämostase sind also komplex und neue antithrombotische Strategien müssen dieser zuvor nicht gekannten Komplexität Rechnung tragen.

Keywords

Serotonin - platelets - serotonylation - haemostasis - vasoconstriction

Schlüsselwörter

Serotonin - Thrombozyten - Serotonylierung - Hämostase - Vasokonstriktion

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