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Physiol. Rev. 79: 1193-1226, 1999;
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Physiological Reviews, Vol. 79, No. 4, October 1999, pp. 1193-1226
Copyright ©1999 by the American Physiological Society

Prostanoid Receptors: Structures, Properties, and Functions

Shuh Narumiya, Yukihiko Sugimoto, and Fumitaka Ushikubi

Department of Pharmacology, Kyoto University Faculty of Medicine, and Department of Physiological Chemistry, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto, Japan

Narumiya, Shuh, Yukihiko Sugimoto, and Fumitaka Ushikubi. Prostanoid Receptors: Structures, Properties, and Functions. J. Neurophysiol. 79: 1193-1226, 1999. Prostanoids are the cyclooxygenase metabolites of arachidonic acid and include prostaglandin (PG) D2, PGE2, PGF2alpha , PGI2, and thromboxne A2. They are synthesized and released upon cell stimulation and act on cells in the vicinity of their synthesis to exert their actions. Receptors mediating the actions of prostanoids were recently identified and cloned. They are G protein-coupled receptors with seven transmembrane domains. There are eight types and subtypes of prostanoid receptors that are encoded by different genes but as a whole constitute a subfamily in the superfamily of the rhodopsin-type receptors. Each of the receptors was expressed in cultured cells, and its ligand-binding properties and signal transduction pathways were characterized. Moreover, domains and amino acid residues conferring the specificities of ligand binding and signal transduction are being clarified. Information also is accumulating as to the distribution of these receptors in the body. It is also becoming clear for some types of receptors how expression of their genes is regulated. Furthermore, the gene for each of the eight types of prostanoid receptor has been disrupted, and mice deficient in each type of receptor are being examined to identify and assess the roles played by each receptor under various physiological and pathophysiological conditions. In this article, we summarize these findings and attempt to give an overview of the current status of research on the prostanoid receptors.




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K. Kuwano, A. Hashino, T. Asaki, T. Hamamoto, T. Yamada, K. Okubo, and K. Kuwabara
2-{4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), an Orally Available and Long-Acting Prostacyclin Receptor Agonist Prodrug
J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1181 - 1188.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
K. Meisdalen, O. F. Dajani, T. Christoffersen, and D. Sandnes
Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors
J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1044 - 1050.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A.-M. Hristovska, L. E. Rasmussen, P. B.L. Hansen, S. S. Nielsen, R. M. Nusing, S. Narumiya, P. Vanhoutte, O. Skott, and B. L. Jensen
Prostaglandin E2 Induces Vascular Relaxation by E-Prostanoid 4 Receptor-Mediated Activation of Endothelial Nitric Oxide Synthase
Hypertension, September 1, 2007; 50(3): 525 - 530.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
V. Bachteeva, E. Fock, E. Lavrova, S. Nikolaeva, S. Gambaryan, and R. Parnova
Prostaglandin E2 inhibits vasotocin-induced osmotic water permeability in the frog urinary bladder by EP1-receptor-mediated activation of NO/cGMP pathway
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R528 - R537.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
G. L. Larsen, J. Loader, C. Fratelli, J.-k. B. Kang, A. Dakhama, and G. N. Colasurdo
Modulation of airway responses by prostaglandins in young and fully grown rabbits
Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L239 - L244.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
S. A. Black Jr., A. H. Palamakumbura, M. Stan, and P. C. Trackman
Tissue-specific Mechanisms for CCN2/CTGF Persistence in Fibrotic Gingiva: INTERACTIONS BETWEEN cAMP AND MAPK SIGNALING PATHWAYS, AND PROSTAGLANDIN E2-EP3 RECEPTOR MEDIATED ACTIVATION OF THE c-JUN N-TERMINAL KINASE
J. Biol. Chem., May 25, 2007; 282(21): 15416 - 15429.
[Abstract] [Full Text] [PDF]


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J. Am. Soc. Nephrol.Home page
H. Francois, C. Facemire, A. Kumar, L. Audoly, B. Koller, and T. Coffman
Role of Microsomal Prostaglandin E Synthase 1 in the Kidney
J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1466 - 1475.
[Abstract] [Full Text] [PDF]


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Stem CellsHome page
J.-Y. Liou, D. P. Ellent, S. Lee, J. Goldsby, B.-S. Ko, N. Matijevic, J.-C. Huang, and K. K. Wu
Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis
Stem Cells, May 1, 2007; 25(5): 1096 - 1103.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y. Sugimoto and S. Narumiya
Prostaglandin E Receptors
J. Biol. Chem., April 20, 2007; 282(16): 11613 - 11617.
[Abstract] [Full Text] [PDF]


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J EndocrinolHome page
N. Kato, K. Kitahara, S. R Rittling, K. Nakashima, D. T Denhardt, H. Kurosawa, Y. Ezura, and M. Noda
Osteopontin deficiency enhances anabolic action of EP4 agonist at a sub-optimal dose in bone
J. Endocrinol., April 1, 2007; 193(1): 171 - 182.
[Abstract] [Full Text] [PDF]


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Arch Otolaryngol Head Neck SurgHome page
V. C. Sandulache, J. B. Chafin, H.-S. Li-Korotky, T. D. Otteson, J. E. Dohar, and P. A. Hebda
Elucidating the Role of Interleukin 1beta and Prostaglandin E2 in Upper Airway Mucosal Wound Healing
Arch Otolaryngol Head Neck Surg, April 1, 2007; 133(4): 365 - 374.
[Abstract] [Full Text] [PDF]


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Adv. Physiol. Educ.Home page
K. M. Eyster
The membrane and lipids as integral participants in signal transduction: lipid signal transduction for the non-lipid biochemist
Advan Physiol Educ, March 1, 2007; 31(1): 5 - 16.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
W. F. van Rodijnen, I. J. Korstjens, N. Legerstee, P. M. ter Wee, and G.-J. Tangelder
Direct vasoconstrictor effect of prostaglandin E2 on renal interlobular arteries: role of the EP3 receptor
Am J Physiol Renal Physiol, March 1, 2007; 292(3): F1094 - F1101.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
M. Sanchez-Alavez, I. Klein, S. E. Brownell, I. V. Tabarean, C. N. Davis, B. Conti, and T. Bartfai
Night eating and obesity in the EP3R-deficient mouse
PNAS, February 20, 2007; 104(8): 3009 - 3014.
[Abstract] [Full Text] [PDF]


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JEMHome page
S. Gross, P. Tilly, D. Hentsch, J.-L. Vonesch, and J.-E. Fabre
Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors
J. Exp. Med., February 19, 2007; 204(2): 311 - 320.
[Abstract] [Full Text] [PDF]


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J DAIRY SCIHome page
Y. Ushida, Y. Shimokawa, T. Toida, H. Matsui, and M. Takase
Bovine {alpha}-Lactalbumin Stimulates Mucus Metabolism in Gastric Mucosa
J Dairy Sci, February 1, 2007; 90(2): 541 - 546.
[Abstract] [Full Text] [PDF]


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Hum ReprodHome page
S. Battersby, K.J. Sales, A.R. Williams, R.A. Anderson, S. Gardner, and H.N. Jabbour
Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway
Hum. Reprod., January 1, 2007; 22(1): 36 - 44.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
R. Nasrallah, H. Xiong, and R. L. Hebert
Renal prostaglandin E2 receptor (EP) expression profile is altered in streptozotocin and B6-Ins2Akita type I diabetic mice
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F278 - F284.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
M. A. Frias, M. C. Rebsamen, C. Gerber-Wicht, and U. Lang
Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy
Cardiovasc Res, January 1, 2007; 73(1): 57 - 65.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
F. Amaya, H. Wang, M. Costigan, A. J. Allchorne, J. P. Hatcher, J. Egerton, T. Stean, V. Morisset, D. Grose, M. J. Gunthorpe, et al.
The Voltage-Gated Sodium Channel Nav1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity
J. Neurosci., December 13, 2006; 26(50): 12852 - 12860.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. Stitham, S. R. Gleim, K. Douville, E. Arehart, and J. Hwa
Versatility and Differential Roles of Cysteine Residues in Human Prostacyclin Receptor Structure and Function
J. Biol. Chem., December 1, 2006; 281(48): 37227 - 37236.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
A. Zhang, Z. Dong, and T. Yang
Prostaglandin D2 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in MDCK cells
Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1332 - F1342.
[Abstract] [Full Text] [PDF]


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JCOHome page
I. Csiki and D. H. Johnson
Did Targeted Therapy Fail Cyclooxygenase Too?
J. Clin. Oncol., October 20, 2006; 24(30): 4798 - 4800.
[Full Text] [PDF]


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J Am Coll CardiolHome page
R. Voswinckel, B. Enke, F. Reichenberger, M. Kohstall, A. Kreckel, S. Krick, H. Gall, T. Gessler, T. Schmehl, H. A. Ghofrani, et al.
Favorable Effects of Inhaled Treprostinil in Severe Pulmonary Hypertension: Results From Randomized Controlled Pilot Studies
J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1672 - 1681.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
A. M. Fulton, X. Ma, and N. Kundu
Targeting Prostaglandin E EP Receptors to Inhibit Metastasis.
Cancer Res., October 15, 2006; 66(20): 9794 - 9797.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
M. N. Ballinger, D. M. Aronoff, T. R. McMillan, K. R. Cooke, K. Olkiewicz, G. B. Toews, M. Peters-Golden, and B. B. Moore
Critical Role of Prostaglandin E2 Overproduction in Impaired Pulmonary Host Response following Bone Marrow Transplantation
J. Immunol., October 15, 2006; 177(8): 5499 - 5508.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
S. Lanza-Jacoby, R. Burd, F. E. Rosato Jr., K. McGuire, J. Little, N. Nougbilly, and S. Miller
Effect of Simultaneous Inhibition of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in HER-2/Neu-Positive Breast Cancer.
Clin. Cancer Res., October 15, 2006; 12(20): 6161 - 6169.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
Y. Akaneya and T. Tsumoto
Bidirectional Trafficking of Prostaglandin E2 Receptors Involved in Long-Term Potentiation in Visual Cortex
J. Neurosci., October 4, 2006; 26(40): 10209 - 10221.
[Abstract] [Full Text] [PDF]


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NeuroscientistHome page
N. Sang and C. Chen
Lipid Signaling and Synaptic Plasticity
Neuroscientist, October 1, 2006; 12(5): 425 - 434.
[Abstract] [PDF]


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J. Appl. Physiol.Home page
M. J. Cowan, T. Coll, and J. H. Shelhamer
Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE2 dependent through decreases in COX-2 and cPLA2 protein levels
J Appl Physiol, October 1, 2006; 101(4): 1127 - 1135.
[Abstract] [Full Text] [PDF]




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