Effects of P2Y(1) and P2Y(12) receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets.

This research examines the effect of specific antagonists on the mechanism of platelet shape change in response to adenosine 5′-diphosphate (ADP) in both human and horse platelets. The study finds that while the antagonists can inhibit this change in both species, the effectiveness varies, with human platelets being more susceptible.

Methodology

• The study uses turbidimetric aggregometry and scanning electron microscopy (SEM) to assess the effects 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)) on ADP-induced platelet shape change. They test this on both human and equine (horse) platelets.
• During the aggregometry phase of the study, they inhibit platelet aggregation using 4-[4-[4(aminoiminomethyl)phenyl]-1-piperazinyl]-1-piperidin acid hydrochloride trihydrate (GR 144053F), an inhibitor of fibrinogen binding, in order to isolate the effect of the antagonists on platelet shape change.

Results

• They conclude from the concentration-response curves and SEM that the shape change of equine platelets is susceptible to inhibition by the P2Y(1) antagonists A3P5PS and MRS-2179, but less so than human platelets. In other words, these antagonists affect the shape change of the platelets in response to ADP, but they are more effective in human platelets than in horse platelets.
• The P2Y(12) antagonist AR-C67085, on the other hand, does not significantly influence the shape change of either equine or human platelets. This suggests that this antagonist is not efficient in inhibiting the platelet shape change.

Implications

• This research adds to the understanding of how different antagonists may influence platelet behavior and responses in different species. This information can improve the understanding of hemostasis and thrombosis in both humans and horses and can inform the development of new therapeutic strategies.
• The differential results between species suggest that the platelet response to ADP and these antagonists can vary significantly between different species, which needs to be taken into account when transferring findings between different species.