Study of aggregation of platelets lacking the P2Y(1) receptor

The recent. generation of mice deficient for the P2Y(1) receptor has allowe d us to directly examine the contribution of this nucleotide receptor in AD P-induced aggregation both in isolated platelets and in vivo thrombosis. St udies utilizing the P2Y(1)-deficient platelets clearly demonstrated that th e P2Y(1) receptor alone is not sufficient for describing the various effect s induced by ADP on platelets. While no increase in intracellular calcium w as observed in the platelets lacking P2Y(1), the ability of ADP to decrease intracellular cAMP was unaltered. An additive and unexpected observation i s the partial aggregation induced by exposure of P2Y(1)-deficient platelets to high levels of ABP. This suggests that additional ADP receptors are exp ressed by platelets and that these receptors can induce partial aggregation of platelets in the absence of measurable changes in intracellular calcium . This review summarizes the recent advances in understanding the mechanism s involved in the platelet response to ADP and examines various hypotheses that attempt to explain the pathway leading to partial aggregation of P2Y(1 ) platelets in response to ADP. Drug Dev. Res. 52:150-155, 2001. (C) 2001 W iley-Liss, Inc.