Prostaglandin F 2 α Facilitates Platelet Activation by Acting on Prostaglandin E 2 Receptor Subtype EP 3 and Thromboxane A 2 Receptor TP in Mice

Platelets play an important role in both physiological hemostasis and pathological thrombosis. Thromboxane (TX) A (2) and prostaglandin (PG) I (2) are well known as a potent stimulator and an inhibitor of platelet function, respectively. Recently, PGE (2) has also been reported to regulate platelet function via PGE (2) receptor subtypes. However, the effect of PGF (2) alpha on platelet function remains to be determined. The aim of the present study was to clarify the effect of PGF (2) alpha on murine platelet function both in vitro and in vivo. Platelets prepared from wild-type mice (WT platelets) expressed several types of prostanoid receptors, including the PGE (2) receptor subtype EP (3) and the TXA (2) receptor TP, while expression of the PGF (2) alpha receptor FP was not detected. In WT platelets, PGF (2) alpha potentiated adenosine diphosphate-induced aggregation in a concentration-dependent manner, while PGF (2) alpha alone did not induce aggregation. In platelets prepared from mice lacking FP, however, PGF (2) alpha-induced potentiation was not significantly different from that in WT platelets. Interestingly, the potentiation was significantly blunted in platelets lacking EP (3) or TP and disappeared completely in platelets lacking both EP (3) and TP. Accordingly, PGF (2) alpha decreased the cyclic adenosine monophosphate level via EP (3) and increased the inositol triphosphate level via TP in WT platelets. Intravenously administered PGF (2) alpha significantly shortened the bleeding time and aggravated arachidonic acid-induced acute thromboembolism in WT mice, suggesting that PGF (2) alpha works as a platelet stimulator also in vivo. In conclusion, PGF (2) alpha potentiates platelet aggregation in vitro via EP (3) and TP but not FP. Accordingly, PGF (2) alpha facilitates hemostasis and thromboembolism in vivo.