The relative importance of the ADP receptors, P2Y12 and P2Y1, in thrombin-induced platelet activation
2003 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 111, no 1-2, 65-73 p.Article in journal (Refereed) Published
The objective of this study was to test the relative importance of the two adenosine diphosphate (ADP) receptors P2Y1 and P2Y12 in thrombin-induced platelet activation using specific receptor antagonists. Blood from healthy volunteers was incubated with MRS2179, a reversible P2Y1 antagonist, or AR-C69931, a reversible P2Y12 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 αIIbβ3, the fibrinogen receptor. Complete inhibition of P2Y12 or P2Y1 abolished the ADP response, but only inhibition of P2Y12 reduced the thrombin-induced response. The relative inhibition of the thrombin response by complete inhibition of P2Y12 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 P2Y12 inhibition decreased due to activation of ADP independent pathways. This study supports P2Y12 as a drug target compared with P2Y1.
Place, publisher, year, edition, pages
2003. Vol. 111, no 1-2, 65-73 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-25241DOI: 10.1016/j.thromres.2003.08.021Local ID: 9680OAI: oai:DiVA.org:liu-25241DiVA: diva2:245568