Prostaglandin F2α Facilitates Platelet Activation by Acting on Prostaglandin E2 Receptor Subtype EP3 and Thromboxane A2 Receptor TP in Mice.

Platelets play an important role in both physiological hemostasis and pathological thrombosis. Thromboxane (TX) A₂ and prostaglandin (PG) I₂ are well known as a potent stimulator and an inhibitor of platelet function, respectively. Recently, PGE₂ has also been reported to regulate platelet function via PGE₂ receptor subtypes. However, the effect of PGF₂α on platelet function remains to be determined. The aim of the present study was to clarify the effect of PGF₂α 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 PGE₂ receptor subtype EP₃ and the TXA₂ receptor TP, while expression of the PGF₂α receptor FP was not detected. In WT platelets, PGF₂α potentiated adenosine diphosphate-induced aggregation in a concentration-dependent manner, while PGF₂α alone did not induce aggregation. In platelets prepared from mice lacking FP, however, PGF₂α-induced potentiation was not significantly different from that in WT platelets. Interestingly, the potentiation was significantly blunted in platelets lacking EP₃ or TP and disappeared completely in platelets lacking both EP₃ and TP. Accordingly, PGF₂α decreased the cyclic adenosine monophosphate level via EP₃ and increased the inositol triphosphate level via TP in WT platelets. Intravenously administered PGF₂α significantly shortened the bleeding time and aggravated arachidonic acid-induced acute thromboembolism in WT mice, suggesting that PGF₂α works as a platelet stimulator also in vivo. In conclusion, PGF₂α potentiates platelet aggregation in vitro via EP₃ and TP but not FP. Accordingly, PGF₂α facilitates hemostasis and thromboembolism in vivo.

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