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The relative importance of the ADP receptors, P2Y12 and P2Y1, in thrombin-induced platelet activation


, : The relative importance of the ADP receptors, P2Y12 and P2Y1, in thrombin-induced platelet activation. Thrombosis Research 111(1-2): 65-73

The objective of this study was to test the relative importance of the two adenosine diphosphate (ADP) receptors P2Y(1) and P2Y(12) in thrombin-induced platelet activation using specific receptor antagonists. Blood from healthy volunteers was incubated with MRS2179, a reversible P2Y(1) antagonist, or AR-C69931, a reversible P2Y(12) antagonist prior to activation with different concentrations of ADP or thrombin. Platelet function in whole blood was assayed by flow cytometry using the antibody PAC-1 to estimate the expression of conformational active alpha(IIb)beta(3), the fibrinogen receptor. Complete inhibition of P2Y(12) or P2Y(1) abolished the ADP response, but only inhibition of P2Y(12) reduced the thrombin-induced response. The relative inhibition of the thrombin response by complete inhibition of P2Y(12) was most pronounced at thrombin concentrations just enough for complete PAR1 cleavage, which is sufficient to release all ADP, giving 70-86% inhibition. Above this concentration, the relative importance of P2Y(12) inhibition decreased due to activation of ADP independent pathways. This study supports P2Y(12) as a drug target compared with P2Y(1).

US$19.90

PMID: 14644082

DOI: 10.1016/j.thromres.2003.08.021


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