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Norel X, Sugimoto Y, Ozen G, Abdelazeem H, Amgoud Y, Bouhadoun A, Bassiouni W, Goepp M, Mani S, Manikpurage HD, Senbel A, Longrois D, Heinemann A, Yao C, Clapp LH. International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E 2 Receptors (EP1-4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions. Pharmacol Rev 2020; 72:910-968. [PMID: 32962984 PMCID: PMC7509579 DOI: 10.1124/pr.120.019331] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
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 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 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.
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Affiliation(s)
- Xavier Norel
- 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.)
| | - Yukihiko Sugimoto
- 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.)
| | - Gulsev Ozen
- 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.)
| | - Heba Abdelazeem
- 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.)
| | - Yasmine Amgoud
- 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.)
| | - Amel Bouhadoun
- 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.)
| | - Wesam Bassiouni
- 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.)
| | - Marie Goepp
- 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.)
| | - Salma Mani
- 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.)
| | - Hasanga D Manikpurage
- 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.)
| | - Amira Senbel
- 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.)
| | - Dan Longrois
- 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.)
| | - Akos Heinemann
- 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.)
| | - Chengcan Yao
- 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.)
| | - Lucie H Clapp
- 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.)
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