The P2Y1 receptor plays an essential role in the platelet shape change induced by collagen when TxA2 formation is prevented.
ADP and TxA2 are secondary agonists which play an important role as cofactors when platelets are activated by agonists such as collagen or thrombin. The aim of the present study was to characterize the role of the ADP receptor P2Y(1) in collagen-induced activation of washed platelets. Inhibition of P2Y(1) alone with the selective antagonist MRS2179 prolonged the lag phase preceding aggregation in response to low or high concentrations of fibrillar collagen, without affecting the maximum amplitude of aggregation or secretion. A combination of MRS2179 and aspirin resulted in complete inhibition of platelet shape change at low and high collagen concentrations, together with a profound decrease in aggregation and secretion. Scanning electron microscopy showed that these platelets had conserved the discoid morphology typical of the resting state. A lack of shape change was also observed in aspirin-treated P2Y(1)- and G(alphaq)-deficient mouse platelets and in delta-storage pool-deficient platelets from Fawn Hooded rats. In contrast, when the second ADP receptor P2Y(12) was inhibited with AR-C69931MX, aspirin-treated platelets were still able to change shape and displayed only a moderate decrease in aggregation and secretion. In conclusion, this study provides evidence that collagen requires not only the TxA2 receptor Tpalpha, but also P2Y(1), to induce platelet shape change.
Mangin
P
P
INSERM U.311, Etablissement Français du Sang-Alsace, Strasbourg, France.
Ohlmann
P
P
Eckly
A
A
Cazenave
J-P
JP
Lanza
F
F
Gachet
C
C
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D004357:Drug Synergism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000502:physiology; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D015539:Platelet Activation; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546383:P2ry1 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D001241:Aspirin