Unité de Pharmacologie Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM) Centre d'Investigation Clinique (CIC) 1406, Centre Hospitalier Universitaire (CHU) Grenoble-Alpes, 38000 Grenoble, France.
Clinique de Médecine Vasculaire, CHU Grenoble-Alpes, 38000 Grenoble, France; INSERM, HP2, 38000 Grenoble, France.
Trends Pharmacol Sci. 2017 Jun;38(6):512-523. doi: 10.1016/j.tips.2017.03.003. Epub 2017 Apr 12.
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, PGI) and its analogs have raised much pharmacological interest. In this review we detail how the PGI signaling pathway is much more complex than was initially anticipated, involving peroxisome proliferator-activated receptors (PPARs), prostaglandin transporters (PGTs), and PGI-thromboxane A (TXA) receptor (IP TP) heterodimerization. We discuss the distinct affinities of PGI analogs for prostanoid receptors. In addition, we introduce the new direct and indirect pharmacological approaches to targeting the PGI 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.
开创性工作表明，从兔和猪主动脉中分离出的一种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）及其类似物引起了广泛的药理学兴趣。在这篇综述中，我们详细介绍了 PGI 信号通路比最初预期的要复杂得多，涉及过氧化物酶体增殖物激活受体（PPARs）、前列腺素转运蛋白（PGTs）和 PGI-血栓烷 A（TXA）受体（IP TP）异二聚化。我们讨论了 PGI 类似物对前列腺素受体的不同亲和力。此外，我们还介绍了在体循环中靶向 PGI 途径的新的直接和间接药理学方法，包括前列腺素 I 受体的非前列腺素激动剂和 PGT 抑制剂，以及使用离子电渗法和纳米结构脂质载体的经皮途径。
