Prostaglandin E2 acts via the EP4 receptor to inhibit platelet aggregation

Background Platelets play a central role in haemostasis. Blood vessel injury leads to platelet aggregation and also invokes an inflammatory response leading to the formation of prostanoids like prostaglandin E2 (PGE2) and prostacyclin (PGI2). It is known that low concentrations of PGE2 enhance and high concentrations inhibit platelet aggregation. PGE2 mediates its effect through four receptors: EP1 (Gαq signalling), EP3 (three isoforms present; signals via Gi, Gs or Gq based on cell type), EP2 and EP4 (Gs signalling). PGI2 is known to inhibit platelet aggregation through its IP receptor (Gs signalling). The role of EP3 in exacerbating platelet aggregation has been well described. However, the role of EP4 which acts via the same G protein coupling like IP has not been explored in detail. The aim of this study was to investigate the role of EP4 in platelet aggregation.