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EP2 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 341

Nomenclature: EP2 receptor

Family: Prostanoid receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 358 14q22.1 PTGER2 prostaglandin E receptor 2 77
Mouse 7 362 14 22.68 cM Ptger2 prostaglandin E receptor 2 (subtype EP2) 47
Rat 7 357 15p14 Ptger2 prostaglandin E receptor 2 19,66
Previous and Unofficial Names Click here for help
PGE receptor EP2 subtype | prostanoid EP2 receptor | Ptger-ep2 | prostaglandin E receptor 2 (subtype EP2), 53kDa
Database Links Click here for help
Specialist databases
GPCRdb pe2r2_human (Hs), pe2r2_mouse (Mm), pe2r2_rat (Rn)
Other databases
Alphafold P43116 (Hs), Q62053 (Mm), Q62928 (Rn)
ChEMBL Target CHEMBL1881 (Hs), CHEMBL2488 (Mm), CHEMBL4909 (Rn)
DrugBank Target P43116 (Hs)
Ensembl Gene ENSG00000125384 (Hs), ENSMUSG00000037759 (Mm), ENSRNOG00000050968 (Rn)
Entrez Gene 5732 (Hs), 19217 (Mm), 81752 (Rn)
Human Protein Atlas ENSG00000125384 (Hs)
KEGG Gene hsa:5732 (Hs), mmu:19217 (Mm), rno:81752 (Rn)
OMIM 176804 (Hs)
Pharos P43116 (Hs)
RefSeq Nucleotide NM_000956 (Hs), NM_008964 (Mm), NM_031088 (Rn)
RefSeq Protein NP_000947 (Hs), NP_032990 (Mm), NP_112350 (Rn)
UniProtKB P43116 (Hs), Q62053 (Mm), Q62928 (Rn)
Wikipedia PTGER2 (Hs)
Natural/Endogenous Ligands Click here for help
PGD2
PGE1
PGE2
PGF2α
PGI2
Comments: PGE2 is the principal endogenous agonist
Potency order of endogenous ligands
PGE2 = PGE1 > PGF2α, PGI2 > PGD2, thromboxane A2

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]PGE2 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Full agonist 7.8 – 8.3 pKd 19,66
⤷ pKd 7.8 – 8.3 [19,66]
[3H]PGE2 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.7 – 7.9 pKd 1,102
⤷ pKd 7.7 – 7.9 (Kd 1.99x10-8 – 1.25x10-8 M) [1,102]
[3H]PGE2 Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Mm Full agonist 7.7 pKd 92
⤷ pKd 7.7 [92]
ONO-AE1-259 Small molecule or natural product Mm Full agonist 8.5 pKi 95
⤷ pKi 8.5 [95]
omidenepag Small molecule or natural product Approved drug Hs Agonist 8.4 pKi 51
⤷ pKi 8.4 (Ki 3.6x10-9 M) [51]
treprostinil Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.4 pKi 96,101
⤷ pKi 8.4 [96,101]
PGN-9856 Small molecule or natural product Hs Agonist 8.3 pKi 24
⤷ pKi 8.3 [24]
PGE2 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 8.2 pKi 19
⤷ pKi 8.2 [19]
PGE1 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.0 pKi 13
⤷ pKi 8.0 (Ki 9.1x10-9 M) [13]
PGE1 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 8.0 pKi 52
⤷ pKi 8.0 [52]
PGE1 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 8.0 pKi 19
⤷ pKi 8.0 [19]
PGE2 Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 7.5 – 8.3 pKi 1,88,102
⤷ pKi 7.5 – 8.3 (Ki 3.16x10-8 – 5.01x10-9 M) [1,88,102]
16,16-dimethyl-PGE2 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.8 pKi 52
⤷ pKi 7.8 [52]
PGE2 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Mm Full agonist 7.4 – 7.9 pKi 52,91,95
⤷ pKi 7.4 – 7.9 [52,91,95]
11-deoxy-PGE1 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 7.5 pKi 19
⤷ pKi 7.5 [19]
misoprostol (free acid form) Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.5 pKi 1
⤷ pKi 7.5 [1]
11-deoxy-PGE1 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.3 pKi 52
⤷ pKi 7.3 [52]
butaprost (free acid form) Small molecule or natural product Click here for species-specific activity table Rn Full agonist 7.2 pKi 19
⤷ pKi 7.2 [19]
19(R)-OH-PGE2 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 6.8 pKi 19
⤷ pKi 6.8 [19]
AH13205 Small molecule or natural product Mm Full agonist 6.6 pKi 52
⤷ pKi 6.6 [52]
butaprost (free acid form) Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.9 – 7.0 pKi 1,88
⤷ pKi 5.9 – 7.0 [1,88]
rivenprost Small molecule or natural product Click here for species-specific activity table Mm Full agonist 6.2 pKi 109
⤷ pKi 6.2 [109]
17-phenyl-ω-trinor-PGE2 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 6.1 pKi 19
⤷ pKi 6.1 [19]
carbacyclin Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 pKi 1
⤷ pKi 6.0 [1]
AH13205 Small molecule or natural product Hs Full agonist 6.0 pKi 88
⤷ pKi 6.0 [88]
isocarbacyclin Small molecule or natural product Click here for species-specific activity table Mm Full agonist 6.0 pKi 52
⤷ pKi 6.0 [52]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Full agonist 5.9 pKi 19
⤷ pKi 5.9 [19]
MB-28767 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.9 pKi 19
⤷ pKi 5.9 [19]
cicaprost Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 5.9 pKi 52
⤷ pKi 5.9 [52]
19(R)-OH-PGE2 Small molecule or natural product Hs Full agonist 5.9 pKi 77
⤷ pKi 5.9 [77]
carbacyclin Small molecule or natural product Click here for species-specific activity table Mm Full agonist 5.8 pKi 52
⤷ pKi 5.8 [52]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 5.8 pKi 52
⤷ pKi 5.8 [52]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 5.7 pKi 1
⤷ pKi 5.7 [1]
ONO-AE1-329 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 5.7 pKi 95
⤷ pKi 5.7 [95]
MB-28767 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.3 – 6.0 pKi 1,88
⤷ pKi 5.3 – 6.0 [1,88]
PGF2α Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 5.2 – 6.0 pKi 1,88
⤷ pKi 5.2 – 6.0 [1,88]
PGF2α Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 5.6 pKi 19
⤷ pKi 5.6 [19]
ONO-AE-248 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 5.4 pKi 95
⤷ pKi 5.4 [95]
PGD2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 5.3 pKi 19
⤷ pKi 5.3 [19]
MRE-269 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 5.2 pKi 56
⤷ pKi 5.2 (Ki 5.8x10-6 M) [56]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 5.1 pKi 19
⤷ pKi 5.1 [19]
PGD2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.0 pKi 88
⤷ pKi 5.0 [88]
misoprostol (methyl ester) Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.0 pKi 1
⤷ pKi 5.0 [1]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 4.9 pKi 1
⤷ pKi 4.9 [1]
evatanepag Small molecule or natural product Ligand has a PDB structure Rn Full agonist 9.5 pEC50 21
⤷ pEC50 9.5 (EC50 3x10-10 M) [21]
taprenepag Small molecule or natural product Ligand has a PDB structure Rn Full agonist 8.3 pIC50 74
⤷ pIC50 8.3 [74]
taprenepag Small molecule or natural product Ligand has a PDB structure Hs Full agonist 8.0 pIC50 74
⤷ pIC50 8.0 [74]
evatanepag Small molecule or natural product Ligand has a PDB structure Rn Full agonist 7.3 pIC50 21
⤷ pIC50 7.3 (IC50 5.01x10-8 M) [21]
View species-specific agonist tables
Agonist Comments
ONO-AE1-259 is the agonist of choice for selectively activating the EP2 receptor.

Butaprost and misoprostol may require enzymatic hydolysis of their ester moiety to achieve full bioactivity.

CP-533536 is a non prostanoid EP2 receptor agonist.

CP-544336 is the biologically-active metabolite of PF-04217329 (Taprenepag isopropyl) [74].

Another non-prostanoid EP2 agonist, o-(o-benzyloxy)-cinnamyl)-cinnamic acid [15], has very slow onset/offset of action on isolated tissue preparations, apparently due to its high lipophilicity [44].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TG4-155 Small molecule or natural product Hs Antagonist 8.6 pKB 41
⤷ pKB 8.6 TG4-155 also has affinity for the human DP1 receptor (pKb = 7.8) [41]
TG7-171 Small molecule or natural product Hs Antagonist 8.6 pKB 31
⤷ pKB 8.6 (KB 2.69x10-9 M) [31]
PF-04852946 Small molecule or natural product Hs Antagonist 8.4 – 8.5 pKB 49
⤷ pKB 8.4 – 8.5 (KB 3.55x10-9 – 2.95x10-9 M) [49]
PF-04418948 Small molecule or natural product Immunopharmacology Ligand Mm Antagonist 8.3 pKB 17
⤷ pKB 8.3 [17]
PF-04418948 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 8.3 pKB 3,17
⤷ pKB 8.3 PF-04418948 has weaker affinity at the EP2-receptor in guinea-pigs [3,17]
TG6-129 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.1 pKB 32
⤷ pKB 8.1 (KB 8.8x10-9 M) [32]
TG11-77 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.0 pKB 5
⤷ pKB 8.0 (KB 9.7x10-9 M) [5]
TG8-260 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 7.9 pKB 6,76
⤷ pKB 7.9 [6,76]
AH6809 Small molecule or natural product Immunopharmacology Ligand Mm Antagonist 6.5 pKi 52
⤷ pKi 6.5 [52]
AH6809 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Rn Antagonist 6.3 pKi 19
⤷ pKi 6.3 [19]
AH6809 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 5.9 pKi 1
⤷ pKi 5.9 [1]
View species-specific antagonist tables
Antagonist Comments
The weak, non-selective EP2 receptor antagonist, AH-6809, has been superceded by PF-04418948. Currently, PF-04418948 is the antagonist of choice for defining EP2 receptor-mediated responses.
PF-04418948 has a lower affinity (pKB = 6.95) for the guinea-pig EP2 receptor compared to the human and murine orthologues [17].
TG4-155 also has high affinity for the DP1 receptor [40-41].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1 [PMID: 20080612] Small molecule or natural product Hs Positive - - 42
⤷ [42]
Allosteric Modulator Comments
Allosteric modulators- both positive (2-piperidinyl phenyl benzamide or trisubstituted pyrimidine core) and negative (compound 1: PubChem CID 664888)- have been identified for the human EP2 receptor (Jiang et al., 2010 [42], 2018 [43], 2020 [39]).
Immunopharmacology Comments
Foudi et al. (2012) [28] review the presence and role of EP1-4 receptors in human inflammation and immune cells. EP2 receptor is discussed in this review of immuno-oncology [2].

PGE2, acting via EP2 and EP4 receptors in synovial tissue appears to contribute to the progression of rheumatoid arthritis in a rat model [105].
Immuno Process Associations
Immuno Process:  Inflammation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  84,91
Tissue Distribution Click here for help
Small intestine, lung, kidney, thymus, uterus and brain.
Species:  Human
Technique:  Northern blot.
References:  13
Kidney: media of arteries, media of arterioles.
Species:  Human
Technique:  Immunohistochemistry.
References:  64
Eye: sclera.
Species:  Human
Technique:  Immunocytochemistry and RT-PCR.
References:  7
Penis: corpus cavernosum.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  54
Mouth: gingival fibroblasts.
Species:  Human
Technique:  RT-PCR.
References:  67
Eye: corneal epithelium and choriocapillaries.
Species:  Human
Technique:  Immunohistochemistry.
References:  83
Myometrial cells.
Species:  Human
Technique:  Immunocytochemistry.
References:  65
Eosinophils.
Species:  Human
Technique:  Immunocytochemistry.
References:  89
Monocyte-derived dendritic cells.
Species:  Human
Technique:  RT-PCR.
References:  55
Aorta.
Species:  Human
Technique:  RT-PCR.
References:  14
Articular cartilage.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  8
Airway smooth muscle cells.
Species:  Human
Technique:  RT-PCR, immunocytochemistry.
References:  23
Airway epithelial cells.
Species:  Human
Technique:  RT-PCR.
References:  33
Peritoneal neutrophils.
Species:  Mouse
Technique:  Northern blot.
References:  106
Spinal cord.
Species:  Rat
Technique:  RT-PCR.
References:  48
Forebrain: meninges, ependymal layer of the lateral ventricle, hippocampus (dentate gyrus, CA1-3), lateral septal nucleus, subfornical organ, piriform cortex, bed nuclei stria terminalis, amygdala, hypothalamus (periventricular zone, ventromedial nucleus), thalamus.
Brainstem: locus coeruleus, area postrema.
Cerebellum: Purkinje cell layers.
Species:  Rat
Technique:  in situ hybridisation.
References:  111
Proximal caput epididymidis.
Species:  Rat
Technique:  RT-PCR and Northern Blotting.
References:  36
Lung, spleen, intestine, skin, kidney, liver, long bone.
Species:  Rat
Technique:  RT-PCR
References:  66
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in non-pigmented epithelial (NPE) cells endogenously expressing the EP2 receptor.
Species:  Human
Tissue:  Non-pigmented epithelial (NPE) cells.
Response measured:  Stimulation of cAMP accumulation.
References:  45
Measurement of cAMP levels in COS-7 cells transfected with the human EP2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  77
Measurement of cAMP levels in COS-7 cells transfected with the rat EP2 receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  66
Measurement of cAMP levels in CHO cells transfected with the human EP2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of cAMP accumulation.
References:  70,103
Measurement of neuronal excitability in rat spinal cord slices endogenously expressing the EP2 receptor.
Species:  Rat
Tissue:  Spinal cord slices.
Response measured:  Depolarisation of neurons.
References:  12
Measurement of Cl- current in rat osteoclasts endogenously expressing the EP2 receptor.
Species:  Rat
Tissue:  Osteoclasts.
Response measured:  Stimulation of Cl- current.
References:  71
Measurement of T-cell factor (Tcf)/lymphoid enhancer factor (Lef) signalling in HEK 293 cells transfected with the human EP2 receptor using a Tcf/Lef-responsive luciferase reporter gene. In addition, measurement of the phosphorylation of glycogen synthase kinase-3 (GSK-3) and Akt kinase.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Activation of Tcf/Lef signalling via a PKA-dependent pathway, phosphorylation of GSK-3 and Akt kinase.
References:  29
Measurement of cAMP formation in cells over-expressing the EP2 receptor.
Species:  Human
Tissue:  C6 glioma cells.
Response measured:  Reduction in TR-FRET signal (Cisbio Bioassay).
References:  41
Physiological Functions Click here for help
Relaxation of bronchial smooth muscle.
Species:  Human
Tissue:  Bronchial preparations.
References:  68
Bronchodilation.
Species:  Mouse
Tissue:  In vivo.
References:  27,86,100
Dilation of arterioles and venules.
Species:  Rat
Tissue:  Stomach.
References:  69
Blood pressure regulation (male and female).
Species:  Mouse
Tissue:  In vivo.
References:  11
Stimulation of renin release and renal vasodilation.
Species:  Mouse
Tissue:  In vivo.
References:  85
Downregulation of protease-activated receptors (PARs).
Species:  Human
Tissue:  Lung fibroblasts.
References:  87
Mediation of spinal inflammatory hyperalgesia.
Species:  Mouse
Tissue:  In vivo.
References:  78
Smooth muscle relaxation.
Species:  Rat
Tissue:  Pulmonary artery rings.
References:  30
Inhibition of sleep.
Species:  Rat
Tissue:  In vivo.
References:  110
Stimulation of calcitonin-gene related peptide (CGRP) release.
Species:  Rat
Tissue:  Primary cultures of trigeminal neurons.
References:  38
Apoptotic cell death.
Species:  Rat
Tissue:  Cortical cells.
References:  98
Bone formation.
Species:  Rat
Tissue:  In vivo.
References:  57,72
Stimulation of cell differentiation (simultaneously with EP4).
Species:  Rat
Tissue:  Primary chondrocytes.
References:  62
Reduction in osteoclast motility.
Species:  Rat
Tissue:  Osteoclasts.
References:  71
Inhibition of phagocytosis.
Species:  Rat
Tissue:  Alveolar macrophages.
References:  9
Apoptotic cell death.
Species:  Rat
Tissue:  Hippocampal cells.
References:  97
Promotion of cell growth.
Species:  Human
Tissue:  Articular chondrocytes.
References:  8
Follicle growth.
Species:  Rat
Tissue:  In vivo (ovary).
References:  25
Cumulus cell expansion in ovarian follicles.
Species:  Mouse
Tissue:  In vivo.
References:  35
Neuroprotection.
Species:  Rat
Tissue:  Hippocampal slices.
References:  61
Inhibition of TNFα formation.
Species:  Mouse
Tissue:  Kupffer cells.
References:  26
Inhibition of TNFα release.
Species:  Human
Tissue:  Alveolar macrophages.
References:  75
Reduction of intraocular pressure.
Species:  Human
Tissue:  Eye.
References:  82
Augementation of G-CSF secretion.
Species:  Human
Tissue:  Airway smooth muscle cells.
References:  23
Suppression of GM-CSF release.
Species:  Human
Tissue:  Airway smooth muscle cells.
References:  22
Relaxation.
Species:  Mouse
Tissue:  Tracheal smooth muscle.
References:  17
Carcinogenesis.
Species:  Human
Tissue:  Prostate cancer cell lines.
References:  40
Inhibition of migration.
Species:  Human
Tissue:  Airway smooth muscle cells.
References:  10
Inhibition of IL-12, IL-23, TNF-α, and MCP-1 release.
Species:  Human
Tissue:  Monocyte-derived dendritic cells.
References:  73
Inhibition of fibroblast to myofibroblast transition.
Species:  Human
Tissue:  Primary fetal and adult lung fibroblasts.
References:  53
Physiological Consequences of Altering Gene Expression Click here for help
EP2 receptor knockout mice exhibit an impaired hypercalcemic response to PGE2.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  59
EP2 receptor knockout mice exhibit impaired tumour angiogenesis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  46
Transgenic mice overexpressing the EP2 receptor exhibit increased keratinocyte proliferation and increased tumour development.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  94
EP2 receptor knockout mice exhibit weak bones.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  4
EP2 receptor knockout mice do not exhibit the bronchodilatory response to PGE2 seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27,86,100
EP2 receptor knockout mice exhibit salt-sensitive hypertension in response to PGE2 and reduced fertility.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  50,99
EP2 receptor knockout mice exhibit reduced PGE2-induced vasodepression compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
EP2 receptor knockout mice exhibit PGE2-mediated renal vasoconstriction, in contrast to the vasodilation seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
EP2 receptor knockout mice exhibit an increase in mean arterial pressure, in contrast to a decrease in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  112
EP2 receptor knockout mice do not exhibit spinal PGE2-evoked hyperalgesia, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  78
EP2 receptor knockout mice exhibit resistance to the inhibitory effect of PGE2 on phagocytosis by alveolar macrophages.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
EP2 receptor knockout mice do not exhibit complete cumulus expansion and hence display impaired fertility.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  35
Osteoblasts from EP2 receptor knockout mice have an impaired ability to stimulate osteoclast formation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  58
EP2 receptor knockout mice exhibit a protective effect against neuronal oxidative damage.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  63
EP2 receptor knockout mice exhibit a reduced increase in aqueous humour protein concentration in the eye and an inhibition of the disruption of the blood-aqueous barrier, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16,18
EP2 receptor knockout mice subjected to permanent focal ischemia exhibit increased excitotoxicity compared to wild-type mice subjected to the same permanent focal ischemia.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  61
Peritoneal neutrophils from EP2 receptor knockout mice do not exhibit PGE2-mediated G-CSF (granulocyte colony-stimulating factor, a hemopoietic growth factor) release, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  90
Tracheal rings from EP2 receptor knockout mice appear to be resistant to cytokine-mediated β2-adrenoceptor desensitisation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  34
EP2 receptor knockout mice exhibit reduced keratinocyte proliferation and reduced tumour development.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  93
Deletion of the EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness.
Species:  Mouse
Tissue:  Skin.
Technique:  Gene targeting in embryonic stem cells.
References:  20
A familial model of Alzheimer's disease deficient in the EP2-receptor displays a reduction in lipid peroxidation that is associated with decreases in amyloid beta peptides and amyloid deposition.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene targeting in embryonic stem cells.
References:  60
Mediation of immune suppression in cancer.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  108
EP2 receptor agonists fail to reduce intraocular pressure in PTGER2-knockout mice.
Species:  Mouse
Tissue:  Eye.
Technique:  Gene knockouts.
References:  79
EP2 receptor knockout mice have higher systolic blood pressure when compared to wild-type mice.
Species:  Mouse
Tissue:  Cardiovascular system.
Technique:  Gene targeting in embryonic stem cells.
References:  75
EP2 receptor deficiency results in impaired cognition, sensorimotor gating, and hippocampal long-term depression.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene targeting in embryonic stem cells.
References:  81
EP2 receptor deficiency impairs hippocampal long-term synaptic plasticity and cognition.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene targeting in embryonic stem cells.
References:  107
EP2 receptor deficiency exacerbates vascular neointimal formation.
Species:  Mouse
Tissue:  Femoral artery.
Technique:  Gene targeting in embryonic stem cells.
References:  113
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0002334 abnormal airway responsiveness PMID: 10846038 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)		 MGI:97794  MP:0001562 abnormal circulating calcium level PMID: 12013525 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0009373 abnormal cumulus expansion PMID: 9751056 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
C.129S6-Ptger2		 MGI:97794  MP:0002912 abnormal excitatory postsynaptic potential PMID: 19012750 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
C.129S6-Ptger2		 MGI:97794  MP:0003691 abnormal microglial cell physiology PMID: 15793296 
Ptger2tm1Brey|Tg(APPswe,PSEN1dE9)85Dbo Ptger2tm1Brey/Ptger2tm1Brey,Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6		 MGI:3525178  MGI:97794  MP:0003633 abnormal nervous system physiology PMID: 16267225 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * BALB/c		 MGI:97794  MP:0003633 abnormal nervous system physiology PMID: 12423256 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0001125 abnormal oocyte morphology PMID: 10468638 
Ptger2tm1Rsz Ptger2tm1Rsz/Ptger2tm1Rsz
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0008396 abnormal osteoclast differentiation PMID: 10830290 
Ptger2tm2Bhk Ptger2tm2Bhk/Ptger2tm2Bhk
involves: 129P2/OlaHsd * 129S/SvEv		 MGI:97794  MP:0005581 abnormal renin activity PMID: 10359563 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0005025 abnormal response to infection PMID: 17330822 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * BALB/c		 MGI:97794  MP:0005025 abnormal response to infection PMID: 12423256 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
B6.129S6-Ptger2		 MGI:97794  MP:0005164 abnormal response to injury PMID: 14715958 
Hrhr|Ptger2tm1Brey Hrhr/Hrhr,Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6 * SKH1		 MGI:96223  MGI:97794  MP:0005501 abnormal skin physiology PMID: 16977324 
Hrhr|Ptger2+|Ptger2tm1Brey Hrhr/Hrhr,Ptger2tm1Brey/Ptger2+
involves: 129S6/SvEvTac * C57BL/6 * SKH1		 MGI:96223  MGI:97794  MP:0005501 abnormal skin physiology PMID: 16977324 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
B6.129S6-Ptger2		 MGI:97794  MP:0001463 abnormal spatial learning PMID: 19012750 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0009648 abnormal superovulation PMID: 11319164 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0001613 abnormal vasodilation PMID: 9930871 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac		 MGI:97794  MP:0001613 abnormal vasodilation PMID: 12167591 
Hrhr|Ptger2tm1Brey Hrhr/Hrhr,Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6 * SKH1		 MGI:96223  MGI:97794  MP:0003448 altered tumor morphology PMID: 16977324 
Ptger2tm1Brey|Tg(APPswe,PSEN1dE9)85Dbo Ptger2tm1Brey/Ptger2tm1Brey,Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6		 MGI:3525178  MGI:97794  MP:0000604 amyloidosis PMID: 16267225 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0002680 decreased corpora lutea number PMID: 10468638 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac		 MGI:97794  MP:0004502 decreased incidence of chemically-induced tumors PMID: 16886605 
Hrhr|Ptger2tm1Brey Hrhr/Hrhr,Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6 * SKH1		 MGI:96223  MGI:97794  MP:0004504 decreased incidence of UV-induced tumors PMID: 16977324 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0001935 decreased litter size PMID: 9930871 
Ptger2tm2Bhk Ptger2tm2Bhk/Ptger2tm2Bhk
involves: 129P2/OlaHsd * 129S/SvEv		 MGI:97794  MP:0001935 decreased litter size PMID: 10359563 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0001935 decreased litter size PMID: 10468638 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0003355 decreased ovulation rate PMID: 10468638 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac		 MGI:97794  MP:0003447 decreased tumor growth/size PMID: 16886605 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0009374 failure of cumulus expansion PMID: 10468638 
Ptger2tm2Bhk Ptger2tm2Bhk/Ptger2tm2Bhk
involves: 129P2/OlaHsd * 129S/SvEv		 MGI:97794  MP:0001596 hypotension PMID: 10359563 
Ptger2tm2Bhk Ptger2tm2Bhk/Ptger2tm2Bhk
involves: 129P2/OlaHsd * 129S/SvEv		 MGI:97794  MP:0000242 impaired fertilization PMID: 10359563 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0000242 impaired fertilization PMID: 10468638 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
B6.129S6-Ptger2		 MGI:97794  MP:0006060 increased cerebral infarction size PMID: 14715958 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0002842 increased systemic arterial blood pressure PMID: 9930871 
Hrhr|Ptger2tm1Brey Hrhr/Hrhr,Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6 * SKH1		 MGI:96223  MGI:97794  MP:0003721 increased tumor growth/size PMID: 16977324 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac		 MGI:97794  MP:0003025 increased vasoconstriction PMID: 12167591 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6		 MGI:97794  MP:0001923 reduced female fertility PMID: 9930871 
Ptger2tm2Bhk Ptger2tm2Bhk/Ptger2tm2Bhk
involves: 129P2/OlaHsd * 129S/SvEv		 MGI:97794  MP:0001923 reduced female fertility PMID: 10359563 
Ptger2tm1Sna Ptger2tm1Sna/Ptger2tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97794  MP:0001923 reduced female fertility PMID: 10468638 
Ptger2tm1Brey Ptger2tm1Brey/Ptger2tm1Brey
C.129S6-Ptger2		 MGI:97794  MP:0001473 reduced long term potentiation PMID: 19012750 
Biologically Significant Variants Click here for help
Type:  Naturally occurring SNPs
Species:  Human
Description:  rs17197 is a more frequent polymorphism in Japanese men with essential hypertension when compared to normotensive counterparts. Proposed to be a genetic marker of essential hypertension.
SNP accession:  rs17197
References:  80
General Comments
For futher information on the properties of the EP2 receptor and its ligands, see the the NC-IUPHAR sponsored review of Woodward et al, 2011 [104].

References

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56. Kuwano K, Hashino A, Asaki T, Hamamoto T, Yamada T, Okubo K, Kuwabara K. (2007) 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, 322 (3): 1181-8. [PMID:17545310]

57. Li M, Ke HZ, Qi H, Healy DR, Li Y, Crawford DT, Paralkar VM, Owen TA, Cameron KO, Lefker BA et al.. (2003) A novel, non-prostanoid EP2 receptor-selective prostaglandin E2 agonist stimulates local bone formation and enhances fracture healing. J Bone Miner Res, 18 (11): 2033-42. [PMID:14606517]

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