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The metabolism of arachidonic acid could produce diverse physiologically important prostanoids, including prostaglandin (PG) D2 (PGD2), PGE2, PGF2, PGI2 (prostacyclin) and thromboxane A2. These prostanoids are generated from the coupling catalytic activities between the upstream cyclooxygenase-1 (COX-1)/-2 (COX-2) and downstream individual prostanoid synthases. The prostanoids are involved in many diseases, such as thrombosis, ischemic stroke, heart arrest, inflammatory diseases, neurodegeneration diseases–among others [1–4]. The diverse functions of prostanoids are mediated by prostanoid receptors, such as thromboxane A2 receptor (TP), PGI2 receptor (IP) and PGE2 receptor (EP) to name a few. In addition, there are four isoforms of EP (EP1–4), which mediate very complicated signal transduction of PGE2 [5]. In this editorial, we will address the structure and ligand binding activities of three …