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Collagen induced human platelet aggregation: serotonin receptor antagonism retards aggregate growth in vitro
1Manchester Metropolitan University, Department of Biological Sciences, United Kingdom.
Objective:
The role of platelet derived serotonin (5-HT) in collagen induced human platelet aggregation was examined both in hirudinised plasma and whole blood. Hirudin was used to maintain normocalcaemia, thereby avoiding erroneous findings often obtained with citrated blood.
Methods:
Platelet aggregation, aggregate growth, and primary platelet aggregation were quantified by optical aggregometry and platelet counting respectively.
Results:
In plasma, platelet aggregation induced by 5-HT (3 microM) in the presence of adrenaline (1 microM) was inhibited by more than 85% by ICI 170809 (3 microM, IC50 0.1 microM), a specific platelet 5-HT2 antagonist. With collagen (0.5 micrograms.ml-1), ICI 170809 retarded the rate of aggregation by 30%, whereas aspirin abolished the response. In contrast, ICI 170809 inhibited collagen induced primary aggregation by less than 10% in both plasma and whole blood.
Conclusions:
(1) 5-HT contributes to collagen induced aggregate growth and 5-HT2 receptor antagonism with ICI 170809 retards the rate of growth. (2) This could explain the efficacy of 5-HT2 antagonists in limiting coronary thrombosis despite the limited role of 5-HT in primary aggregation.