Key result
P2Y1 antagonists inhibited the shape change of equine platelets, though less so than human platelets, whereas the P2Y12 antagonist did not significantly influence shape change in either species.
Why the study?
Do P2Y1 and P2Y12 receptor antagonists inhibit ADP-induced shape change in equine and human platelets?
Do P2Y1 and P2Y12 receptor antagonists inhibit ADP-induced shape change in equine and human platelets?
P2Y1 receptors, rather than P2Y12 receptors, mediate ADP-induced platelet shape change, with species-specific differences in susceptibility to P2Y1 antagonists.
Equine platelet data should not guide therapy; leaves open P2Y1 as target with species-specific differences.
Platelet activation by adenosine 5' -diphosphate (ADP) is via both P2Y(1 )and P2Y(12) receptors and leads to shape change and aggregation. The effects on ADP-induced platelet shape change of two P2Y(1) antagonists, adenosine 3'-phosphate, 5'-phosphosulfate (A3P5PS) and 2-deoxy-N(6)-methyladenosine 3', 5'-diphosphate (MRS-2179) and a P2Y(12) antagonist 2-propylthio-D-beta,gamma-dichloromethylene-adenosine 5'-triphosphate (AR-C67085MX) were determined by turbidimetric aggregometry and scanning electron microscopy (SEM) on equine and human platelets. The platelet aggregation was inhibited during aggregometry by 4-[4-[4(aminoiminomethyl)phenyl]-1-piperazinyl]-1-piperidin acid hydrochloride trihydrate (GR 144053F), an inhibitor of fibrinogen binding. From aggregation profiles, concentration-response curves and SEM we conclude that the shape change of equine platelets was susceptible to inhibition by the P2Y(1) antagonists A3P5PS and MRS-2179, but less so than human platelets. The P2Y(12) antagonist AR-C67085 did not influence significantly the shape change of either equine or human platelets.
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Mateos-Trigos et al. (2002) studied this question. P2Y1 antagonists (A3P5PS and MRS-2179) and P2Y12 antagonist (AR-C67085MX) vs. Human platelets was evaluated on ADP-induced platelet shape change. P2Y1 antagonists inhibited the shape change of equine platelets, though less so than human platelets, whereas the P2Y12 antagonist did not significantly influence shape change in either species.
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