Inhibition of platelet aggregation and the release of P-selectin from platelets by cilostazol

To evaluate the in vitro effects of cilostazol, a phosphodiesterase III inh ibitor, on platelet responses, we measured platelet aggregation and the lev els of soluble P-selectin, a glycoprotein present on the oc-granule membran e in resting platelets, and cAMP. Platelet-rich plasma and washed platelets from healthy human volunteers were treated with cilostazol (5, 25 and 50 C IM) Platelet-rich plasma was stimulated by ADP (1 and 5 muM) or collagen (5 mug/ml). Washed platelets were stimulated by thrombin (4 U/ml) in the pres ence or absence of 1 CIM forskolin. In vehicle-treated samples, soluble P-s electin levels in response to 1 muM ADP-induced primary aggregation were si milar to those of circulating levels of healthy volunteers but the levels i n response to 5 muM ADP-induced secondary aggregation and collagen-induced aggregation increased markedly compared to those in response to primary agg regation. This result suggests that P-selectin is released from platelets a ccording to the extent of platelet aggregation. Cilostazol inhibited platel et aggregation as well as P-selectin release in a concentration-dependent m anner. Cilostazol inhibited completely thrombin-induced aggregation in the presence of 1 muM forskolin, when cAMP levels were two-fold higher than tho se in the absence of forskolin. Cilostazol, which increases intracellular c AMP in platelets, may be useful in the treatment of arterial occlusive dise ases. (C) 2001 Elsevier Science Ltd. All rights reserved.