Collagen induced human platelet aggregation: serotonin receptor antagonism retards aggregate growth in vitro.
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.
Menys
V C
VC
Manchester Metropolitan University, Department of Biological Sciences, United Kingdom.
D001081:Apyrase / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006629:Hirudins / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D011804:Quinolines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D006629:Hirudins; D011804:Quinolines; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D012701:Serotonin; C060632:ICI 170809; D003094:Collagen; D001081:Apyrase; D001241:Aspirin; C060225:desirudin; D004837:Epinephrine