Both the ADP receptors P2Y 1 and P2Y 12 , play a role in controlling shape change in human platelets.

Two types of ADP receptors, P2Y[SUB1] and P2Y[SUB12] are involved in platelet aggregation. The P2X[SUB1] receptor is also present but its role, in terms of platelet function, is not yet defined. The aim of this study was to establish if the ADP receptors, P2Y[SUB1], P2Y[SUB12] and P2X[SUB1] play a role in controlling platelet shape change (PSC) in human platelets. PSC is an early phase of platelet activation that precedes aggregation. Using a high-resolution channelyzer, PSC was assessed by measuring the median platelet volume (MPV). The P2Y[SUB1] receptor antagonist MRS 2179 (1.06 - 10.25μmol/l) blocked ADP-induced PSC (by 100%). The median IC[SUB50] was 3.16 μmol/l. MRS 2179 also significantly (P = 0.01) inhibited PSC induced by the combination of ADP + serotonin (5HT). The P2Y[SUB12] receptor antagonist AR-C69931MX significantly inhibited (at 10s,P = 0.009; 15 s, P = 0.001 and 30 s, P = 0.015) ADP-induced PSC. The P2X[SUB1] receptor antagonist TNP-ATP had no significant effect on ADP- or ADP + 5HT-induced PSC. We conclude that the IC[SUB50] of a P2Y[SUB1] -blocker can be derived because of the high-resolution and reproducibility of the channelyzer technique. In addition to the P2Y[SUB1] purinoceptor, the P2Y[SUB12] receptor appears to be involved in ADP-induced PSC since this process was significantly inhibited by AR-C69931MX. The channelyzer technique may be more reliable than optical aggregometry to assess PSC. [ABSTRACT FROM AUTHOR]