Effects of P2Y(1) and P2Y(12) receptor antagonists on ADP-induced shape change of equine platelets: comparison with human platelets.
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.
Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, UK. gm239@hermes.cam.ac.uk
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Mateos-Trigos
R J
RJ
Evans
M F
MF
Heath
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D005340:Fibrinogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D006736:Horses / Q000097:blood*; D006801:Humans; D008565:Membrane Proteins; D008855:Microscopy, Electron, Scanning; D010724:Phosphoadenosine Phosphosulfate / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010979:Platelet Function Tests; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12
C117445:AR C67085MX; D008565:Membrane Proteins; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D000249:Adenosine Monophosphate; D010724:Phosphoadenosine Phosphosulfate; D000244:Adenosine Diphosphate; D005340:Fibrinogen