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EP3 receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 342

Nomenclature: EP3 receptor

Family: Prostanoid receptors

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 7 390 1p31.1 PTGER3 prostaglandin E receptor 3 2,57-58,60,104,148
Mouse 7 365 3 81.32 cM Ptger3 prostaglandin E receptor 3 (subtype EP3) 119,126
Rat 7 365 2q45 Ptger3 prostaglandin E receptor 3 16,127
Gene and Protein Information Comments
Many isoforms are described for the EP3 receptor due to mRNA splicing variants. NC-IUPHAR nomenclature for these isoforms should be respected- see the "Biologically Significant Variants" section below.
Previous and Unofficial Names Click here for help
PGE receptor EP3 subtype | prostaglandin E receptor 3 | prostanoid EP3 receptor
Database Links Click here for help
Specialist databases
GPCRDB pe2r3_human (Hs), pe2r3_mouse (Mm), pe2r3_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of EP3 receptor bound to misoprostol-FA
PDB Id:  6M9T
Ligand:  misoprostol (free acid form)
Resolution:  2.5Å
Species:  Human
References:  10
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human prostaglandin E receptor EP3 bound to prostaglandin E2
PDB Id:  6AK3
Ligand:  PGE2
Resolution:  2.9Å
Species:  Human
References:  83
Natural/Endogenous Ligands Click here for help
PGD2
PGE1
PGE2
PGF
PGI2
Comments: PGE2 is the principal endogenous agonist
Potency order of endogenous ligands
PGE2, PGE1 > PGF, 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 9.1 pKd 16
pKd 9.1 [16]
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 8.9 pKd 54
pKd 8.9 (Kd 1.4x10-9 M) [54]
[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 8.2 – 9.5 pKd 1,146
pKd 8.2 – 9.5 (Kd 7x10-9 – 3x10-10 M) [1,146]
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 Hs Full agonist 8.2 – 9.1 pKd 118,145-146
pKd 8.7 (Kd 2.1x10-9 M) EP3-II & -III isoforms [118]
pKd 8.2 – 9.1 (Kd 6x10-9 – 8x10-10 M) EP3-I isoform [118,145-146]
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 7.8 – 9.1 pKd 16,88-89,118
pKd 9.0 (Kd 1.1x10-9 M) EP3γ isoform [118]
pKd 8.3 – 9.1 (Kd 5x10-9 – 8x10-10 M) EP3α isoform [16,89,118]
pKd 7.8 – 8.4 (Kd 1.5x10-8 – 3.9x10-9 M) EP3β isoform [88-89]
MB-28767 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.9 pKi 1
pKi 9.9 (Ki 1.4x10-10 M) EP3-III isoform [1]
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 Hs Full agonist 9.5 pKi 1
pKi 9.5 (Ki 3.3x10-10 M) EP3-III isoform [1]
sulprostone Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.5 pKi 1
pKi 9.5 (Ki 3.5x10-10 M) EP3-III isoform [1]
sulprostone Small molecule or natural product Click here for species-specific activity table Mm Full agonist 9.2 pKi 54
pKi 9.2 [54]
MB-28767 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 9.1 pKi 54
pKi 9.1 (Ki 7x10-10 M) [54]
sulprostone Small molecule or natural product Click here for species-specific activity table Rn Full agonist 9.1 pKi 16
pKi 9.1 (Ki 7x10-10 M) [16]
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 9.1 pKi 54
pKi 9.1 (Ki 8.5x10-10 M) [54]
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 9.0 pKi 54
pKi 9.0 (Ki 1x10-9 M) [54]
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 9.0 pKi 16
pKi 9.0 (Ki 1x10-9 M) [16]
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 9.0 pKi 16
pKi 9.0 [16]
11-deoxy-PGE1 Small molecule or natural product Click here for species-specific activity table Mm Partial agonist 8.8 pKi 54
pKi 8.8 (Ki 1.5x10-9 M) [54]
16,16-dimethyl-PGE2 Small molecule or natural product Click here for species-specific activity table Mm Partial agonist 8.7 pKi 54
pKi 8.7 (Ki 1.9x10-9 M) [54]
GR 63799 Small molecule or natural product Mm Partial agonist 8.7 pKi 54
pKi 8.7 (Ki 1.9x10-9 M) [54]
11-deoxy-PGE1 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 8.5 pKi 16
pKi 8.5 [16]
ONO-8713 Small molecule or natural product Rn Full agonist 8.5 pKi 16
pKi 8.5 (Ki 3.2x10-9 M) EP3α isoform [16]
17-phenyl-ω-trinor-PGE2 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 8.4 pKi 54
pKi 8.4 (Ki 3.7x10-9 M) [54]
17-phenyl-ω-trinor-PGE2 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 8.4 pKi 16
pKi 8.4 (Ki 4.3x10-9 M) EP3α isoform [16]
cloprostenol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.4 pKi 1
pKi 8.4 (Ki 4.4x10-9 M) EP3-III isoform [1]
GR 63799 Small molecule or natural product Hs Agonist 8.3 pKi 1
pKi 8.3 (Ki 4.8x10-9 M) EP3-III isoform [1]
misoprostol (free acid form) Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.1 pKi 1
pKi 8.1 (Ki 7.9x10-9 M) EP3-III isoform [1]
ONO-AE-248 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.8 – 8.1 pKi 123,154
pKi 7.8 – 8.1 (Ki 1.5x10-8 – 7.5x10-9 M) EP3α isoform [123,154]
ONO-AP-324 Small molecule or natural product Mm Partial agonist 8.0 pKi 48
pKi 8.0 (Ki 1.1x10-8 M) EP3α isoform [48]
enprostil Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.9 pKi 1
pKi 7.9 (Ki 1.2x10-8 M) EP3-III isoform [1]
carbacyclin Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.8 pKi 1
pKi 7.8 (Ki 1.4x10-8 M) EP3-III isoform [1]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 7.7 pKi 54
pKi 7.7 (Ki 2.2x10-8 M) [54]
STA2 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.6 pKi 54
pKi 7.6 (Ki 2.3x10-8 M) [54]
carbacyclin Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.5 pKi 54
pKi 7.5 (Ki 3.1x10-8 M) [54]
isocarbacyclin Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.5 pKi 54
pKi 7.5 (Ki 3.1x10-8 M) [54]
PGF Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist 7.4 pKi 1
pKi 7.4 (Ki 3.8x10-8 M) EP3-III isoform [1]
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 5.9 – 8.9 pKi 16
pKi 8.9 (Ki 1.3x10-9 M) EP3α isoform [16]
pKi 5.9 [16]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Full agonist 7.3 pKi 16
pKi 7.3 (Ki 4.7x10-8 M) EP3α isoform [16]
rivenprost Small molecule or natural product Click here for species-specific activity table Mm Partial agonist 7.3 pKi 153
pKi 7.3 (Ki 5.6x10-8 M) [153]
GR 63799 Small molecule or natural product Rn Agonist 7.1 pKi 16
pKi 7.1 (Ki 7.3x10-8 M) EP3α isoform [16]
enprostil Small molecule or natural product Click here for species-specific activity table Rn Full agonist 7.1 pKi 16
pKi 7.1 (Ki 7.4x10-8 M) EP3α isoform [16]
PGF Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Mm Full agonist 7.1 pKi 54
pKi 7.1 (Ki 7.5x10-8 M) [54]
I-BOP Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.0 pKi 54
pKi 7.0 (Ki 1x10-7 M) [54]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 6.7 – 7.3 pKi 1,145
pKi 7.3 (Ki 5.6x10-8 M) EP3-III isoform [1]
pKi 6.7 (Ki 2.08x10-7 M) EP3-I isoform [145]
cicaprost Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 6.8 pKi 54
pKi 6.8 (Ki 1.7x10-7 M) [54]
PGF Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Rn Full agonist 6.7 pKi 16
pKi 6.7 (Ki 2.13x10-7 M) EP3α isoform [16]
cicaprost Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 6.6 pKi 1
pKi 6.6 (Ki 2.55x10-7 M) EP3-III isoform [1]
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 Mm Full agonist 6.6 pKi 54
pKi 6.6 (Ki 2.8x10-7 M) [54]
misoprostol (methyl ester) Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 6.5 pKi 1
pKi 6.5 (Ki 3.19x10-7 M) EP3-III isoform [1]
beraprost Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.2 pKi 64
pKi 6.2 (Ki 6.8x10-7 M) [64]
fluprostenol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 pKi 1
pKi 6.2 (Ki 7.08x10-7 M) EP3-III isoform [1]
ONO-AE1-329 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 5.9 pKi 123
pKi 5.9 (Ki 1.2x10-6 M) EP3α isoform [123]
butaprost (free acid form) Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 pKi 1
pKi 5.8 (Ki 1.643x10-6 M) EP3-III isoform [1]
treprostinil Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.6 pKi 145
pKi 5.6 (Ki 2.5x10-6 M) EP3-I isoform [145]
butaprost (free acid form) Small molecule or natural product Click here for species-specific activity table Rn Full agonist 4.9 pKi 16
pKi 4.9 (Ki 1.18x10-5 M) EP3α isoform [16]
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]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 4.8 pKi 16
pKi 4.8 (Ki 1.62x10-5 M) EP3α isoform [16]
SC46275 Small molecule or natural product Cp Full agonist 10.4 pEC50 108
pEC50 10.4 (EC50 4x10-11 M) [108]
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 9.4 pEC50 16
pEC50 9.4 (EC50 4.1x10-10 M) EP3α isoform [16]
sulprostone Small molecule or natural product Click here for species-specific activity table Rn Full agonist 9.4 pEC50 16
pEC50 9.4 (EC50 4.2x10-10 M) [16]
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 9.4 pEC50 16
pEC50 9.4 (EC50 4.5x10-10 M) EP3α isoform [16]
MB-28767 Small molecule or natural product Click here for species-specific activity table Rn Full agonist 9.3 pEC50 16
pEC50 9.3 (EC50 5.5x10-10 M) EP3α isoform [16]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Full agonist 9.2 pEC50 16
pEC50 9.2 (EC50 6.3x10-10 M) EP3α isoform [16]
sulprostone Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.9 pEC50 115
pEC50 8.9 (EC50 1.4x10-9 M) [115]
SC46275 Small molecule or natural product Rn Full agonist 8.7 pEC50 40
pEC50 8.7 (EC50 1.8x10-9 M) [40]
enprostil Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.4 pEC50 115
pEC50 8.4 (EC50 3.7x10-9 M) [115]
PGF Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Rn Full agonist 8.4 pEC50 16
pEC50 8.4 (EC50 4.2x10-9 M) EP3α isoform [16]
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 7.9 pEC50 16
pEC50 7.9 (EC50 1.3x10-8 M) EP3α isoform [16]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 6.8 pEC50 16
pEC50 6.8 (EC50 1.49x10-7 M) EP3α isoform [16]
cloprostenol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.7 pEC50 115
pEC50 6.7 (EC50 2.21x10-7 M) [115]
ONO-AE-248 Small molecule or natural product Hs Full agonist 5.6 – 6.7 pEC50 29,70
pEC50 5.6 – 6.7 (EC50 2.3x10-6 – 2x10-7 M) [29,70]
SC46275 Small molecule or natural product Clf Full agonist 11.0 pIC50 136
pIC50 11.0 (IC50 1x10-11 M) [136]
View species-specific agonist tables
Agonist Comments
The pKi for endogenous agonists, PGE2 and PGE1 are dependent on EP3 receptor isoform: PGE2 pKi 9.1 for EP3III [1]; PGE1 pKi 9.0 (rat) for EP3alpha [16].

Further potent and selective ligands of the human EP3 receptor have been identified, see [32-33,51].

Sulprostone has been commonly used as an EP3 agonist but shows considerable EP1 agonism [22]; SC46275 [48,108] and ONO-AE-248 [19] are more selective agents. ONO-AP-324 is closely related to the non-prostanoid prostacyclin mimetic ONO-1301; it shows EP3 partial agonism on smooth muscle preparations, while retaining a small degree of IP agonism [48].

Although M&B28767 is a highly potent EP3 agonist, it also shows significant TP agonism [66]

In the mouse, the three EP3 isoforms show similar ligand binding properties but have different signal transduction properties [121].

Reference [114] uses human platelet preparations instead of transfected cells.

Agonist misoprostol is an effective gastric ulcer therapy [102,106].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
L-826266 Small molecule or natural product Hs Antagonist 8.4 pKB 20
pKB 8.4 (KB 4.5x10-9 M) [20]
ONO-AE3-240 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 9.6 pKi 4
pKi 9.6 [4]
DG-041 Small molecule or natural product Hs Antagonist 8.4 – 10.1 pKi 50,118
pKi 10.1 (Ki 8x10-11 M) EP3-I isoform [118]
pKi 9.9 (Ki 1.2x10-10 M) EP3-II isoform [118]
pKi 9.5 (Ki 3x10-10 M) EP3-III isoform [118]
pKi 8.4 (Ki 3.9x10-9 M) [50]
L-798,106 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 7.8 – 9.7 pKi 50-51,118
pKi 7.8 – 9.7 (Ki 1.7x10-8 – 2.1x10-10 M) EP3-III isoform [50-51,118]
L-826266 Small molecule or natural product Hs Antagonist 8.0 – 9.1 pKi 20,49,51
pKi 9.1 (Ki 8x10-10 M) EP3-III isoform (pKi=8.04 in the presence of HSA) [51]
pKi 8.0 – 9.1 (Ki 1.1x10-8 – 8x10-10 M) [20,49]
ONO-AE2-227 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 7.7 pKi 85
pKi 7.7 (Ki 2.1x10-8 M) [85]
ONO-AE3-208 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Antagonist 7.5 pKi 52
pKi 7.5 (Ki 3x10-8 M) [52]
ONO-8711 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 7.2 pKi 144
pKi 7.2 (Ki 6.7x10-8 M) [144]
SC-51322 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 1
pKi 6.2 (Ki 7x10-7 M) EP3-III isoform [1]
AH6809 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 5.8 pKi 1
pKi 5.8 (Ki 1.6x10-6 M) EP3-III isoform [1]
ONO-8713 Small molecule or natural product Click here for species-specific activity table Mm Antagonist <5.0 pKi 144
pKi <5.0 (Ki >1x10-5 M) [144]
ONO-AE5-599 Small molecule or natural product Mm Antagonist 9.7 pIC50 3
pIC50 9.7 (IC50 1.9x10-10 M) [3]
ONO-AE3-240 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 8.8 pIC50 4
pIC50 8.8 (IC50 1.5x10-9 M) [4]
ONO-AE2-227 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 6.8 pIC50 85
pIC50 6.8 (IC50 1.6x10-7 M) [85]
View species-specific antagonist tables
Antagonist Comments
Further potent and selective ligands of the human EP3 receptor have been identified, see [32-33,51].

L-796,106 (pA2 = 7.4 - 8.10) [21,40] and ONO-AE3-240 [4,125] are recently developed selective EP3 antagonists.

Care is required in the use of L-826266 and DG-041 owing to their high lipophilicity [49].

Antagonist DG-04, a potential inhibitor of human platelet aggregation, is currently in human clinical trials for the treatment of atherothrombosis [30,116].
Immunopharmacology Comments
Foudi et al. (2012) [28] review the presence and role of EP1-4 receptors in human inflammation and immune cells. Studies in mice suggest that EP3 receptors may participate in reducing allergic reactivity.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0001660 fever generation IDA
GO:0006954 inflammatory response IBA
GO:0031622 positive regulation of fever generation ISS
GO:2000391 positive regulation of neutrophil extravasation IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0031622 positive regulation of fever generation ISS
GO:2000391 positive regulation of neutrophil extravasation IMP
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes
GO:0031623 receptor internalization IMP
GO:1990767 prostaglandin receptor internalization IMP
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:2000391 positive regulation of neutrophil extravasation IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0071347 cellular response to interleukin-1 IEP
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  5,90,107,112
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  5,147
Tissue Distribution Click here for help
Kidney and uterus.
Species:  Human
Technique:  RT-PCR.
References:  5
Thalamus: anterior, ventromedial, laterodorsal, paraventricular and central medial nuclei.
Species:  Human
Technique:  in situ hybridisation.
References:  122
Kidney: glomeruli, Tamm-Horsfall negative late distal convoluted tubules, connecting segments, cortical and medullary collecting ducts, media and endothelial cells of arteries and arterioles.
Species:  Human
Technique:  Immunohistochemistry.
References:  81
Kidney: cortical and outer medullary collecting duct, medullary thick ascending limb.
Species:  Human
Technique:  in situ hybridization.
References:  18
Eye: corneal endothelium and keratocytes, trabecular cells, ciliary epithelium, conjunctival and iridal stroma cells, retinal Muller cells.
Species:  Human
Technique:  Immunohistochemistry.
References:  109
In intestinal mucosa, EP3 receptors are expressed on epithelia at the apex of crypts.
Species:  Human
Technique:  in situ hybridization, immunohistochemistry.
References:  124
EP3-Ib, EP3-II, EP3-III, EP3-IV and EP3-e mRNA in vascular smooth muscle and gastric fundic mucosa cells.
Species:  Human
Technique:  RT-PCR, Southern blot, immunohistochemistry.
References:  59
EP3 receptor is primarily expressed in the cortical and outer medullary collecting duct, as well as in the medullary thick ascending limb .
Species:  Human
Technique:  in situ hybridization.
References:  17-18
EP3 receptor labeling was primarily observed in the corneal endothelium and keratocytes, trabecular cells, ciliary epithelium, and conjunctival and iridal stroma cells, and EP(3) was found, in addition, in retinal Müller cells.
Species:  Human
Technique:  RT-PCR, immunohistochemistry.
References:  109
In pregnant myometrium EP3 receptor was only expressed by stromal and endothelial cells.
Species:  Human
Technique:  Western blot, immunohistochemistry.
References:  69
In myometrium EP3 receptor expression is increased in placenta, chorion and amnion with labour.
Species:  Human
Technique:  in situ hybridization., immunohistochemistry.
References:  140
There were no differences between non-pregnant and non-labouring pregnant subjects in mRNA expression of EP3-II,-III and -VI. However, there is decreased mRNA expression of lower-uterine segment EP3 receptor isoforms II and VI during labour.
Species:  Human
Technique:  RT-PCR.
References:  68
Mouth: gingival fibroblasts.
Species:  Human
Technique:  RT-PCR.
References:  92
Myometrium.
Species:  Human
Technique:  Northern blotting.
References:  74
EP3 receptor mRNA is expressed in the tubular epithelium of the outer medulla, especially in the thick ascending limb and cortical collecting ducts.
Species:  Mouse
Technique:  in situ hybridization.
References:  120-121
Aorta.
Species:  Mouse
Technique:  RNase protection assay.
References:  155
Gastrointestinal tract: neurons of the myenteric ganglia throughout the tract > fundic gland epithelial cells, except for surface mucous cells in the stomach.
Species:  Mouse
Technique:  in situ hybridization.
References:  82
In tumor obtained after Sarcoma-180 cells implantation, EP3 mRNA are localized in both sarcoma and stromal cells but not in endothelial cells.
Species:  Mouse
Technique:  in situ hybridization.
References:  4
Main cell species expressing EP3 in the skin is keratinocytes.
Species:  Mouse
Technique:  Immunohistochemistry, histology in receptor knockout mice
References:  38
Intense signals for EP3 transcripts were detected in neurons of the myenteric ganglia throughout the tract. Moderate EP3 mRNA expression was also observed in fundic gland epithelial cells.
Species:  Mouse
Technique:  in situ hybridization.
References:  82
Ammon's horn, the preoptic nuclei, lateral hypothalamic area, dorsomedial hypothalamic nucleus, lateral mammillary nucleus, entopeduncular nucleus, substantia nigra pars compacta, locus coeruleus and raphe nuclei > mitral cell layer of the main olfactory bulb, layer V of the entorhinal and parasubicular cortices, layers V and VI of the cerebral neocortex, nuclei of the diagonal band, magnocellular preoptic nucleus, globus pallidus and lateral parabrachial nucleus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  122
Kidney: tubules in the outer medulla and in the distal tubules in the cortex.
Species:  Mouse
Technique:  in situ hybridization.
References:  120
EP3 receptor expression in the mouse preoptic region by in situ hybridization and isolated the corresponding area by laser capture microdissection. Real-time RT-PCR analysis of microdissected tissue revealed a predominant expression of the EP3-α isoform
Species:  Mouse
Technique:  in situ hybridization.
References:  142
Kidney: outer medulla > cortex > papilla.
Species:  Rat
Technique:  RNase protection assay.
References:  45
EP3-like immunoreactivity was observed in the median preoptic nucleus, medial preoptic area, parastrial nucleus, compact part of the dorsomedial hypothalamic nucleus, and dorsal part of the premammillary nucleus.
Species:  Rat
Technique:  Western blot, immunohistochemistry.
References:  84,86
Gastrointestinal tract: small intestine and colon (muscle layers of the deep intestinal wall), stomach (gastric mucosal layer containing epithelial cells).
Species:  Rat
Technique:  Northern blotting.
References:  23
Tissue Distribution Comments
Prostanoid receptor antibodies, are not very selective for immunochemistry experiments, results with other experimental approaches in parallel are necessary.
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 Ca2+ levels in CHO cells transfected with the human EP3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Increase in Ca2+ concentration.
References:  5
Measurement of cAMP levels in CHO cells transfected with the mouse EP3 receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  119
Measurement of Ba2+ currents in rat melanotrophs endogenously expressing the EP3 receptor.
Species:  Rat
Tissue:  Melanotrophs.
Response measured:  Inhibition of P/Q- and L-type voltage-dependent Ca2+ channels.
References:  134
EP3-I isoform stimulation, cAMP dependent mechanism.
Species:  Human
Tissue:  CHO cells.
Response measured:  Acid extrusion.
References:  99
Measurement of cAMP levels in cells transfected with the human EP3 receptor (isoforms -Ia, -Ib -II, -III, -IV).
Species:  Human
Tissue:  CHO cells.
Response measured:  Decreased intracellular cAMP concentration and increased intracellular concentration of Ca2+ .
References:  5
Measurement of cAMP levels in cells transfected with the EP3-Ia, EP3-II and EP3-III isoforms.
Species:  Human
Tissue:  HEK cells.
Response measured:  Inhibition of cAMP accumulation.
References:  44
PGE2-induced desensitization of cloned EP3 isoforms.
Species:  Human
Tissue:  CHO cells.
Response measured:  EP3-II slow and persistent desensitization; EP3-III and -IV rapid and transient desensitization.
References:  5
PGE2-induced internalization of cloned EP3 isoforms.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  EP3-I internalized almost completely, EP3-II, (EP3-V, EP3-VI and EP3-f ??) internalized to a lesser extent and EP3-III and EP3-IV did not internalize.
References:  15
EP3 mediated inhibition of CaV2 voltage-gated Ca2+ channel currents (ICa)
Species:  Mouse
Tissue:  Adrenal chromaffin cells.
Response measured: 
References:  46
Measurement of cAMP levels in cells transfected with the rat EP3β receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-elicited cAMP formation after stimulation with PGE2, M&B28767 or sulprostone.
References:  88
Measurement of cAMP and calcium levels in cells transfected with the rat EP3α or EP3β receptor.
Species:  Rat
Tissue:  TKC2, COS-7 cells.
Response measured:  cAMP formation was attenuated by over-expression of EP3α receptor; free cytosolic calcium was increased via EP3β receptor activation.
References:  130
PGE2 induces different activation of Gi protein and desensitization depending of the EP3 isoforms (-α, -β, - γ) stimulated.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  Three orders lower concentrations of agonists were required for EP3α, than EP3β for activation of Gi protein. EP3α, undergoes both short and long term agonist-induced desensitization, whereas EP3β undergoes neither short nor long term desensitization.
References:  41-42,87
PGE2 induces different activation of Gi protein and desensitization depending of the EP3 isoforms (-α, -β, - γ) stimulated.
Species:  Rat
Tissue:  HEK293 cells.
Response measured:  EP3α and EP3β are functionally coupled to Gi and reduced forskolin-induced cAMP-formation. Repeated exposure of cells expressing the EP3α isoform to M&B28767 led to internalization of the receptor to intracellular endocytotic vesicles. By contrast, that was not observed with EP3β.
References:  89
PGE2 induces liver myofibroblast contraction via a [Ca2+]i independent PKC-mediated pathway through the EP3 receptor.
Species:  Rat
Tissue:  Liver myofibroblasts.
Response measured:  This effect appears to involve an enhancement of the Ca2+ sensitization through a Ca2+-independent, novel PKCδ and/or PKCε-mediated pathway.
References:  13
Measurement of cAMP levels in cells transfected with the rat EP3α receptor.
Species:  Rat
Tissue:  HEK293 cells.
Response measured:  Inhibition of forskolin-elicited cAMP formation after stimulation with PGE2.
References:  16
Measurement of PLC activity and Ca2+ levels in cultured human myometrial cells endogenously expressing the EP3 receptors.
Species:  Human
Tissue:  Cultured myometrial cells.
Response measured:  Activation of PLC and increase in Ca2+ level.
References:  9
Physiological Functions Click here for help
Airway constriction.
Species:  Mouse
Tissue:  In vivo.
References:  135
Constriction of venules.
Species:  Rat
Tissue:  Stomach.
References:  95
Blood pressure regulation (male only).
Species:  Mouse
Tissue:  In vivo.
References:  12
Renal vasoconstriction.
Species:  Mouse
Tissue:  In vivo.
References:  113
Duodenal HCO3- secretion.
Species:  Rat
Tissue:  Duodenum.
References:  133
Mechanical hyperalgesia.
Species:  Rat
Tissue:  In vivo.
References:  97
Inhibition of gastric acid secretion.
Species:  Rat
Tissue:  In vivo (stomach).
References:  53
Inhibition of lipolysis.
Species:  Rat
Tissue:  Isolated adipocytes.
References:  117
Inhibition of noradrenaline release.
Species:  Rat
Tissue:  Isolated trachea.
References:  103
Inhibition of a neurogenic vasopressor response.
Species:  Rat
Tissue:  In vivo.
References:  73
Thermal hyperalgesia.
Species:  Rat
Tissue:  In vivo.
References:  39,96
Stimulation of noradrenaline release.
Species:  Rat
Tissue:  In vivo.
References:  150-151
Inhibition of gastric noradrenaline release.
Species:  Rat
Tissue:  Isolated stomach.
References:  149
Inhibition of vagally mediated gastric acid secretion.
Species:  Rat
Tissue:  In vivo.
References:  152
Inhibition of acetylcholine release.
Species:  Human
Tissue:  Isolated bronchi.
References:  105
Thermal hyperalgesia.
Species:  Mouse
Tissue:  In vivo.
References:  78
Intestinal protection.
Species:  Rat
Tissue:  In vivo (intestine).
References:  61-62
Hypertension and tachycardia via sympathetic nerve activity.
Species:  Rat
Tissue:  In vivo.
References:  6
Mediation of PAF-induced edema formation.
Species:  Rat
Tissue:  Isolated lung.
References:  35
Nitric oxide (NO) release via Rho-kinase activation.
Species:  Mouse
Tissue:  Spinal cord slices.
References:  75
PGE2 inhibits monoamine release via presynaptic EP(3) receptors.
Species:  Mouse
Tissue:  Hippocampus, cortex.
References:  25,36
PGE2 inhibits monoamine release via presynaptic EP(3) receptors.
Species:  Rat
Tissue:  Cortex, vas deferens, trachea, stomach.
References:  25,36,103,149
PGE2 suppresses allergic inflammation by activation of the EP3 receptor.
Species:  Mouse
Tissue:  Lung.
References:  63
PGE2 induces fever via the EP3 receptor.
Species:  Mouse
Tissue:  Preoptic hypothalamus.
References:  31,37
PGE2-induced decrease in acid secretion via EP3 receptor.
Species:  Mouse
Tissue:  Stomach.
References:  91
Vasoconstriction.
Species:  Human
Tissue:  Pulmonary artery, intercostal artery, mammary artery.
References:  29,70,93,101
PGE2-induced depolarization of sensory nerves.
Species:  Human
Tissue:  Vagus nerves.
References:  72
PGE2 involvement in atherothrombosis +/- effect of EP3 antagonists.
Species:  Human
Tissue:  Platelet aggregation.
References:  30,111,116
EP3 is the primary receptor subtype that mediates PGE(2) induced contractility in human pregnant myometrium at term.
Species:  Human
Tissue:  Myomertium.
References:  8
PGE2-induced depolarization of sensory nerves.
Species:  Mouse
Tissue:  Vagus nerves.
References:  72
Involvement of EP3 receptors in the regulation of duodenal HCO3- secretion as well as the maintenance of the mucosal integrity of the duodenum against acid injury.
Species:  Mouse
Tissue:  Duodenum.
References:  3
EP3 receptor has been identified as important in mediating beneficial effects after established nephritis in mice.
Species:  Mouse
Tissue:  kidney, glomeruli.
References:  65
Misoprostol, an agonist of EP3 receptor, decreased perfusion of the cortex and medulla, with both renal artery and medullary interstitial infusion.
Species:  Rat
Tissue:  Kidney.
References:  14
Reduction in infarct size.
Species:  Rat
Tissue:  Myocardium.
References:  154
Vasoconstriction.
Species:  Rat
Tissue:  Mesenteric artery.
References:  55
PGE2 inhibits monoamine release via presynaptic EP(3) receptors.
Species:  Human
Tissue:  Atrial, saphenous vein, pulmonary artery.
References:  79-80
PGE2-to-EP3 signaling pathway is mediated mainly by the EP3γ isoform in the motor neurons of mice.
Species:  Mouse
Tissue:  Motor neurons
References:  56
Physiological Consequences of Altering Gene Expression Click here for help
EP3 receptor knockout mice exhibit reduced PGE2