To evaluate the in vitro effects of
cilostazol, a
phosphodiesterase III inhibitor, on platelet responses, we measured platelet aggregation and the levels of soluble
P-selectin, a
glycoprotein present on the alpha-granule membrane in resting platelets, and cAMP. Platelet-rich plasma and washed platelets from healthy human volunteers were treated with
cilostazol (5, 25 and 50 microM). Platelet-rich plasma was stimulated by
ADP (1 and 5 microM) or
collagen (5 microg/ml). Washed platelets were stimulated by
thrombin (4 U/ml) in the presence or absence of 1 microM
forskolin. In vehicle-treated samples, soluble
P-selectin levels in response to 1 microM
ADP-induced primary aggregation were similar to those of circulating levels of healthy volunteers but the levels in response to 5 microM
ADP-induced secondary aggregation and
collagen-induced aggregation increased markedly compared to those in response to primary aggregation. This result suggests that
P-selectin is released from platelets according to the extent of platelet aggregation.
Cilostazol inhibited platelet aggregation as well as
P-selectin release in a concentration-dependent manner.
Cilostazol inhibited completely
thrombin-induced aggregation in the presence of 1 microM
forskolin, when cAMP levels were two-fold higher than those in the absence of
forskolin.
Cilostazol, which increases intracellular cAMP in platelets, may be useful in the treatment of
arterial occlusive diseases.