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

Abstract

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 - g , n -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.