Abstract
Prostaglandins are derived from arachidonic acid metabolism through cyclooxygenase activities. Among prostaglandins (PGs), prostacyclin (PGI2) and PGE2 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. PGI2 and PGE2 exert their biologic actions by binding to their respective receptors, namely prostacyclin receptor (IP) and prostaglandin E2 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 STATEMENTIn this review, we present an update of the pathophysiologic role of the prostacyclin receptor, prostaglandin E2 receptor (EP) 1, EP2, EP3, and EP4 receptors when activated by the two main prostaglandins, namely prostacyclin and prostaglandin E2, 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.
Highlights
In comparison with other prostanoids, prostaglandin (PG) E2 and prostacyclin (PGI2) are dramatically increased during inflammatory processes and pathologic conditions in different organs
In this review we focused on the effects of prostaglandin E2 (PGE2) and PGI2 in thrombogenesis, it should be noted that other prostanoids, such as thromboxane A2 (TxA2) and PGD2, are involved in the regulation of thrombogenesis by inducing (TP receptor) and inhibiting (DP1 receptor) platelet aggregation, respectively (Armstrong, 1996; Song et al, 2012; Crescente et al, 2019)
Because clinical pharmacology/therapeutic interventions require both a reductionist and an integrated approach, we present the effects of PGE2 and the involvement of different E2 receptor (EP)-receptor types in the lung at three levels of integration: 1) cell types/tissue; 2) pathophysiologic processes that are common to many lung diseases [e.g., contraction or proliferation of smooth muscle cell (SMC); pulmonary vascular remodeling (Lundequist et al, 2010)]; and 3) specific diseases
Summary
Significance Statement——In this review, we present an update of the pathophysiologic role of the prostacyclin receptor, prostaglandin E2 receptor (EP) 1, EP2, EP3, and EP4 receptors when activated by the two main prostaglandins, namely prostacyclin and prostaglan- published results in each tissue and/or pathology din E2, produced during inflammatory conditions in should facilitate the choice of the most appropriate human and rodents. This comparison of the model for the future studies
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