国际基础和临床药理学联合会。CIX. 人源和啮齿动物前列腺素 E 受体（EP1-4）和前列环素受体（IP）之间的差异和相似性：在病理生理条件下的特定作用。
International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E Receptors (EP1-4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions.
机构信息
Université de Paris, Institut National de la Sante et de la Recherche Medicale (INSERM), UMR-S 1148, CHU X. Bichat, Paris, France (X.N., G.O., H.A., Y.A., A.B., S.M., H.D.M., A.S., D.L.); Université Sorbonne Paris Nord, Villetaneuse, France (X.N., H.A., Y.A., A.B., S.M., D.L.); Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan (Y.S.); Istanbul University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey (G.O.); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.S., H.A., W.B.); Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom (C.Y., M.G.); Institut Supérieur de Biotechnologie de Monastir (ISBM), Université de Monastir, Monastir, Tunisia (S.M.); CHU X. Bichat, AP-HP, Paris, France (D.L.); Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Graz, Austria (A.H.); and Centre for Cardiovascular Physiology & Pharmacology, University College London, London, United Kingdom (L.H.C.)
Université de Paris, Institut National de la Sante et de la Recherche Medicale (INSERM), UMR-S 1148, CHU X. Bichat, Paris, France (X.N., G.O., H.A., Y.A., A.B., S.M., H.D.M., A.S., D.L.); Université Sorbonne Paris Nord, Villetaneuse, France (X.N., H.A., Y.A., A.B., S.M., D.L.); Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan (Y.S.); Istanbul University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey (G.O.); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt (A.S., H.A., W.B.); Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom (C.Y., M.G.); Institut Supérieur de Biotechnologie de Monastir (ISBM), Université de Monastir, Monastir, Tunisia (S.M.); CHU X. Bichat, AP-HP, Paris, France (D.L.); Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Graz, Austria (A.H.); and Centre for Cardiovascular Physiology & Pharmacology, University College London, London, United Kingdom (L.H.C.).
出版信息
Pharmacol Rev. 2020 Oct;72(4):910-968. doi: 10.1124/pr.120.019331.
Prostaglandins are derived from arachidonic acid metabolism through cyclooxygenase activities. Among prostaglandins (PGs), prostacyclin (PGI) and PGE are strongly involved in the regulation of homeostasis and main physiologic functions. In addition, the synthesis of these two prostaglandins is significantly increased during inflammation. PGI and PGE exert their biologic actions by binding to their respective receptors, namely prostacyclin receptor (IP) and prostaglandin E receptor (EP) 1-4, which belong to the family of G-protein-coupled receptors. IP and EP1-4 receptors are widely distributed in the body and thus play various physiologic and pathophysiologic roles. In this review, we discuss the recent advances in studies using pharmacological approaches, genetically modified animals, and genome-wide association studies regarding the roles of IP and EP1-4 receptors in the immune, cardiovascular, nervous, gastrointestinal, respiratory, genitourinary, and musculoskeletal systems. In particular, we highlight similarities and differences between human and rodents in terms of the specific roles of IP and EP1-4 receptors and their downstream signaling pathways, functions, and activities for each biologic system. We also highlight the potential novel therapeutic benefit of targeting IP and EP1-4 receptors in several diseases based on the scientific advances, animal models, and human studies. SIGNIFICANCE STATEMENT: In this review, we present an update of the pathophysiologic role of the prostacyclin receptor, prostaglandin E receptor (EP) 1, EP2, EP3, and EP4 receptors when activated by the two main prostaglandins, namely prostacyclin and prostaglandin E, produced during inflammatory conditions in human and rodents. In addition, this comparison of the published results in each tissue and/or pathology should facilitate the choice of the most appropriate model for the future studies.
前列腺素通过环氧化酶活性来源于花生四烯酸代谢。在前列腺素（PGs）中，前列环素（PGI）和 PGE 强烈参与内环境稳态和主要生理功能的调节。此外，这两种前列腺素的合成在炎症期间显著增加。PGI 和 PGE 通过与其各自的受体（即前列环素受体（IP）和前列腺素 E 受体（EP）1-4）结合发挥其生物学作用，这些受体属于 G 蛋白偶联受体家族。IP 和 EP1-4 受体广泛分布于全身，因此发挥各种生理和病理生理作用。在这篇综述中，我们讨论了使用药理学方法、基因修饰动物和全基因组关联研究的最新进展，这些研究涉及 IP 和 EP1-4 受体在免疫、心血管、神经、胃肠道、呼吸、泌尿生殖和肌肉骨骼系统中的作用。特别是，我们强调了人与啮齿动物在 IP 和 EP1-4 受体及其下游信号通路、功能和活性方面的特定作用方面的相似性和差异性，以及它们在每个生物系统中的作用。我们还根据科学进展、动物模型和人类研究强调了针对 IP 和 EP1-4 受体的潜在新型治疗益处。
意义陈述
在这篇综述中，我们介绍了在人类和啮齿动物中，在炎症条件下产生的两种主要前列腺素，即前列环素和前列腺素 E 激活时，前列腺素受体、前列腺素 E 受体（EP）1、EP2、EP3 和 EP4 受体的病理生理作用。此外，对每个组织和/或病理学中已发表结果的比较应有助于为未来研究选择最合适的模型。
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