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aProperties of the three main platelet ADP-receptors identified thus far.

aProperties of the three main platelet ADP-receptors identified thus far.

tor in platelet function. Table 3 summarizes the key features of the three ADP receptors previously discussed.

Respective Roles of the ADP Receptors in Platelet Function

Based on a series of observations, it is believed that P2Y1 is responsible for platelet shape change, which is an important event in platelet activation. In fact, P2Y1 alone can trigger a clear but transient aggregation response, which is probably necessary during the initial phases of platelet aggregation. Nevertheless, this receptor is not sufficient for full platelet aggregation, and the P2Y12 receptor appears to be responsible for the completion and amplification of platelet aggregation induced by ADP, as well as by other agonists. P2Y12 plays a specific role in the activation of the GP IIb/IIIa receptor after ADP stimulation, and it also confers stability to the platelet macroaggregate (68).

In such a scenario, it appears that while P2Y1 plays a specific role in the initial platelet activation response, characterized by shape change and formation of long filopodia, it is the P2Y12 receptor that is involved in the amplification of platelet aggregation induced by other agonists such as thrombin, chemokines, epinephrine, or TXA2. Therefore, there is a strong biological rationale behind the pharmacological antagonism of the ADP receptors.

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