Pioneering work demonstrated that an unstable substance isolated from rabbit and pig aortas could relax arterial smooth muscle and inhibit platelet aggregation. Since then, prostacyclin (prostaglandin I2, PGI₂) and its analogs have raised much pharmacological interest. In this review we detail how the PGI₂ signaling pathway is much more complex than was initially anticipated, involving peroxisome proliferator-activated receptors (PPARs), prostaglandin transporters (PGTs), and PGI₂–thromboxane A₂ (TXA₂) receptor (IP TP) heterodimerization. We discuss the distinct affinities of PGI₂ analogs for prostanoid receptors. In addition, we introduce the new direct and indirect pharmacological approaches to targeting the PGI₂ pathway within the systemic circulation, including non-prostanoid agonists of the prostacyclin receptor (IP) and PGT inhibitors, as well as transcutaneous pathways using iontophoresis and nanostructured lipid carriers.

开拓性工作表明，从兔和猪主动脉中分离出的不稳定物质可以使动脉平滑肌松弛并抑制血小板聚集。从那时起，前列环素（前列腺素I2，PGI ₂）及其类似物引起了许多药理学兴趣。在这篇综述中，我们详细介绍了PGI ₂信号通路如何比最初预期的复杂得多，涉及过氧化物酶体增殖物激活受体（PPAR），前列腺素转运蛋白（PGT）和PGI _2-血栓烷A ₂（TXA ₂）受体（IP） TP）异二聚。我们讨论了PGI ₂的独特亲和力前列腺素受体类似物。此外，我们介绍了针对全身循环内PGI ₂途径的新的直接和间接药理方法，包括前列环素受体（IP）和PGT抑制剂的非类前列腺素激动剂，以及使用离子电渗疗法和纳米结构脂质载体的经皮途径。