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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

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 7 390 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
Alphafold P43115 (Hs), P30557 (Mm), P34980 (Rn)
ChEMBL Target CHEMBL3710 (Hs), CHEMBL4336 (Mm), CHEMBL5674 (Rn)
DrugBank Target P43115 (Hs)
Ensembl Gene ENSG00000050628 (Hs), ENSMUSG00000040016 (Mm), ENSRNOG00000010325 (Rn)
Entrez Gene 5733 (Hs), 19218 (Mm), 24929 (Rn)
Human Protein Atlas ENSG00000050628 (Hs)
KEGG Gene hsa:5733 (Hs), mmu:19218 (Mm), rno:24929 (Rn)
OMIM 176806 (Hs)
Pharos P43115 (Hs)
RefSeq Nucleotide NM_198716 (Hs), NM_001126044 (Hs), NM_198714 (Hs), NM_198717 (Hs), NM_198718 (Hs), NM_198719 (Hs), NR_028293 (Hs), NR_028294 (Hs), NM_198715 (Hs), NM_011196 (Mm), NM_012704 (Rn)
RefSeq Protein NP_001119516 (Hs), NP_035326 (Mm), NP_036836 (Rn)
UniProtKB P43115 (Hs), P30557 (Mm), P34980 (Rn)
Wikipedia PTGER3 (Hs)
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
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 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]
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 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]
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 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]
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 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]
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 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
Immuno Process:  Immune regulation
Immuno Process:  Antigen presentation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cytokine production & signalling
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
Thalamus: anterior, ventromedial, laterodorsal, paraventricular and central medial nuclei.
Species:  Human
Technique:  in situ hybridisation.
References:  122
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
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
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
Myometrium.
Species:  Human
Technique:  Northern blotting.
References:  74
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
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
Kidney and uterus.
Species:  Human
Technique:  RT-PCR.
References:  5
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
Aorta.
Species:  Mouse
Technique:  RNase protection assay.
References:  155
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
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
Main cell species expressing EP3 in the skin is keratinocytes.
Species:  Mouse
Technique:  Immunohistochemistry, histology in receptor knockout mice
References:  38
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
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
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
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
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
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-induced depolarization of sensory nerves.
Species:  Human
Tissue:  Vagus nerves.
References:  72
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 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
Inhibition of tumor growth and angiogenesis by antagonism of EP3 is impaired in EP3 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  4
EP3 receptor knockout mice exhibit reduced PGE2-induced airway responsiveness compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  135
EP3 receptor knockout mice exhibit increased basal renal blood flow, decreased renal vascular resistance and increased PGE2-mediated renal vasodilation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
EP3 receptor knockout mice do not exhibit the protective intestinal effects of dimethyl-PGE2 against indomethacin, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  61-62
EP3 receptor knockout mice exhibit reduced pulmonary edema formation compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  35
EP3 receptor knockout mice show that there may be a possible link between PGE2 and anorexia/cachexia development.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  143
EP3 receptor knockout mice exhibit a reduction in furosemide-stimulated enhancement of diuresis and electrolyte excretion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  94
EP3 receptor knockout mice exhibit reduced inflammatory nociception.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  138
Mice lacking the EP3 receptor display increased bleeding tendency and decreased susceptibility to thromboembolism.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  71
EP3 knockout mice display enhanced allergic asthma when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  63
EP3 knockout mice do not exhibit the PGE2-mediated duodenal HCO3- secretion seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  128,131-132
Abnormal pain threshold; EP3 receptor knockout mice do not exhibit the PGE2-mediated thermal hyperalgesia seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  78
EP3 receptors are involved in stroke injury through the enhancement of inflammatory and apoptotic reactions in the ischemic cortex.
Species:  Mouse
Tissue:  Brain, cerebral cortex.
Technique:  Gene knockouts, pharmacology.
References:  43
In mice lacking EP3 receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent.
Species:  Mouse
Tissue:  Intestinal smooth-muscle cells.
Technique:  Gene knockouts.
References:  137
PGE2 produced by the vascular wall facilitates arterial thrombosis and platelet aggregation via EP3 receptor activation.
Species:  Mouse
Tissue:  Platelets, jugular veins, carotid arteries.
Technique:  Gene knockouts.
References:  26,34
PGE2 induced depolarization of sensory nerves are virtually abolished in EP3-deficient mice.
Species:  Mouse
Tissue:  Vagus nerves.
Technique:  Gene knockouts.
References:  72
Abnormal response to infection; EP3 receptor knockout mice exhibit decreased circulating adrenocorticotropin level and impaired LPS-induced ACTH release (impaired HPA axis activation).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  76
Abnormal response/metabolism to endogenous compounds and impaired febrile response in EP3 knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
Abnormal urine osmolality in EP3 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
Abnormal body temperature homeostasis (EP3 knockout mice display impaired fever generation when compared to the wild-type) and abnormal physiological response to xenobiotic.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  67,98,141
Decreased renal vascular resistance in EP3 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
EP3(-/-) mice were protected from mortality after infection with Streptococcus pneumoniae or LPS injection.
Species:  Mouse
Tissue:  Alveolar macrophage, lung neutrophils, blood leukocytes.
Technique:  Gene knockouts.
References:  7
EP3 receptor-mediated modulation of bladder activity.
Species:  Mouse
Tissue:  Bladder.
Technique:  Gene knockouts.
References:  77
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
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
B6.129P2-Ptger3		 MGI:97795  MP:0001777 abnormal body temperature regulation PMID: 12837930 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
involves: 129P2/OlaHsd		 MGI:97795  MP:0001970 abnormal pain threshold PMID: 11375261 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
B6.129P2-Ptger3		 MGI:97795  MP:0008872 abnormal physiological response to xenobiotic PMID: 12837930 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
involves: 129P2/OlaHsd		 MGI:97795  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 19940926 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
B6.129P2-Ptger3		 MGI:97795  MP:0005025 abnormal response to infection PMID: 12642666 
Ptger3tm1Cof Ptger3tm1Cof/Ptger3tm1Cof
either: (involves: 129P2/OlaHsd * C57BL/6 * DBA/2) or (involves: 129P2/OlaHsd * 129S/SvEv)		 MGI:97795  MP:0002987 abnormal urine osmolality PMID: 9843913 
Ptger3tm1Csml|Tg(Nes-cre)1Kln Ptger3tm1Csml/Ptger3tm1Csml,Tg(Nes-cre)1Kln/?
involves: 129S4/SvJae * C57BL/6 * SJL		 MGI:2176172  MGI:97795  MP:0005534 decreased body temperature PMID: 17676060 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
B6.129P2-Ptger3		 MGI:97795  MP:0002664 decreased circulating adrenocorticotropin level PMID: 12642666 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:97795  MP:0003829 impaired febrile response PMID: 9751056 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
B6.129P2-Ptger3		 MGI:97795  MP:0003829 impaired febrile response PMID: 12837930 
Ptger3tm1Csml Ptger3tm1Csml/Ptger3tm1Csml
involves: 129S4/SvJae * C57BL/6		 MGI:97795  MP:0003829 impaired febrile response PMID: 17676060 
Ptger3tm1Csml|Tg(Nes-cre)1Kln Ptger3tm1Csml/Ptger3tm1Csml,Tg(Nes-cre)1Kln/?
involves: 129S4/SvJae * C57BL/6 * SJL		 MGI:2176172  MGI:97795  MP:0003829 impaired febrile response PMID: 17676060 
Ptger3tm1Sna Ptger3tm1Sna/Ptger3tm1Sna
involves: 129P2/OlaHsd		 MGI:97795  MP:0003829 impaired febrile response PMID: 19940926 
Ptger3tm1Cof Ptger3tm1Cof/Ptger3tm1Cof
involves: 129P2/OlaHsd * C57BL/6		 MGI:97795  MP:0005048 thrombosis PMID: 17242161 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Stevens-Johnson syndrome
Synonyms: Severe cutaneous adverse reaction, susceptibility to [OMIM: 608579]
Disease Ontology: DOID:0050426
OMIM: 608579
Orphanet: ORPHA36426
Comments:  An association has been demonstrated between polymorphisms in PTGER3 and Stevens-Johnson syndrome
References:  139
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Rat
Description:  EP3β
Amino acids:  362
References:  88,100
Type:  Splice variant
Species:  Human
Description:  EP3-I
Amino acids:  390
Nucleotide accession:  NM_198714, NM_198719
References:  15,47,57-59,104,110
Type:  Splice variant
Species:  Human
Description:  EP3-III
Amino acids:  365
Nucleotide accession:  NM_198717
References:  15,47,57-59,104,110
Type:  Splice variant
Species:  Human
Description:  EP3-IV
Nucleotide accession:  NM_198716
References:  15,47,57-59,110
Type:  Splice variant
Species:  Mouse
Description:  EP3α. Amino acid length for this variant is 365/366.
Amino acids:  365
References:  42,58,121
Type:  Splice variant
Species:  Human
Description:  EP3e
Amino acids:  418
References:  15,58-59
Type:  Splice variant
Species:  Rat
Description:  EP3γ
Amino acids:  365
References:  100,129
Type:  Splice variant
Species:  Rat
Description:  EP3α
Amino acids:  366
Protein accession:  NP_036836
References:  16,100,129
Type:  Splice variant
Species:  Mouse
Description:  EP3β. Amino acid length for this variant is 361/362.
Amino acids:  361
References:  42,121
Type:  Splice variant
Species:  Rat
Description:  EP3δ
Amino acids:  343
References:  100
Type:  Splice variant
Species:  Human
Description:  EP3-II
Amino acids:  388
Nucleotide accession:  NM_198715
References:  15,47,57-59,104,110
Type:  Splice variant
Species:  Mouse
Description:  EP3γ. Amino acid length for this variant is 363-365.
References:  24,42
Biologically Significant Variant Comments
List of EP3 variants with their respective mRNA and protein RefSeq IDs

Human variants:
EP3-Ia (transcript variant 9, NM_198719; NP_942012), EP3-Ib (transcript variant 4, NM_198714; NP_942007), EP3-Ic (transcript variant 11, NM_001126044; NP_001119516), EP3-II (transcript variant 5, NM_198715;NP_942008), EP3-III (transcript variant 7, NM_198717; NP_942010), EP3-IV (transcript variant 6, NM_198716; NP_942009), EP3-e (transcript variant 8, NM_198718, NP_942011)

Mouse variants:
EP3α (isoform CRA_a) EDL11860, EP3β (isoform CRA_c) EDL11862;NP_035326, EP3γ (isoform CRA_b) EDL11861

Rat variants:
EP3α (isoform CRA_b) EDL82565, EP3β (isoform CRA_c) EDL82566;NP_036836EP3γ (isoform CRA_a) EDL82564, EP3δ (isoform CRA_d) EDL82567

Notes: Isoform CRA_ a, b, c and d correspond to the nomenclature found in NCBI Nucleotide.
NCBI describe human transcript variants 1-3 (corresponding previously to EP3-V; EP3-VI and EP3-f) as "non-coding because the use of the 5'-most supported translational start codon, as used in variant 7, renders the transcript a candidate for nonsense-mediated mRNA decay".
In the article by Kotani et al (1997) EP3e amino acid sequence is incomplete, 25 amino acids are missing [58].

References

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1. Abramovitz M, Adam M, Boie Y, Carrière M, Denis D, Godbout C, Lamontagne S, Rochette C, Sawyer N, Tremblay NM et al.. (2000) The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta, 1483 (2): 285-93. [PMID:10634944]

2. Adam M, Boie Y, Rushmore TH, Müller G, Bastien L, McKee KT, Metters KM, Abramovitz M. (1994) Cloning and expression of three isoforms of the human EP3 prostanoid receptor. FEBS Lett, 338: 170-174. [PMID:8307176]

3. Aihara E, Nomura Y, Sasaki Y, Ise F, Kita K, Takeuchi K. (2007) Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate secretion in rats. Life Sci, 80 (26): 2446-53. [PMID:17512019]

4. Amano H, Hayashi I, Endo H, Kitasato H, Yamashina S, Maruyama T, Kobayashi M, Satoh K, Narita M, Sugimoto Y et al.. (2003) Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. J Exp Med, 197 (2): 221-32. [PMID:12538661]

5. An S, Yang J, So SW, Zeng L, Goetzl EJ. (1994) Isoforms of the EP3 subtype of human prostaglandin E2 receptor transduce both intracellular calcium and cAMP signals. Biochemistry, 33 (48): 14496-502. [PMID:7981210]

6. Ariumi H, Takano Y, Masumi A, Takahashi S, Hirabara Y, Honda K, Saito R, Kamiya HO. (2002) Roles of the central prostaglandin EP3 receptors in cardiovascular regulation in rats. Neurosci Lett, 324 (1): 61-4. [PMID:11983295]

7. Aronoff DM, Lewis C, Serezani CH, Eaton KA, Goel D, Phipps JC, Peters-Golden M, Mancuso P. (2009) E-prostanoid 3 receptor deletion improves pulmonary host defense and protects mice from death in severe Streptococcus pneumoniae infection. J Immunol, 183 (4): 2642-9. [PMID:19635910]

8. Arulkumaran S, Kandola MK, Hoffman B, Hanyaloglu AC, Johnson MR, Bennett PR. (2012) The roles of prostaglandin EP 1 and 3 receptors in the control of human myometrial contractility. J Clin Endocrinol Metab, 97 (2): 489-98. [PMID:22162473]

9. Asbóth G, Phaneuf S, Europe-Finner GN, Toth M, Bernal AL. (1996) Prostaglandin E2 activates phospholipase C and elevates intracellular calcium in cultured myometrial cells: involvement of EP1 and EP3 receptor subtypes. Endocrinology, 137: 2572-2579. [PMID:8641211]

10. Audet M, White KL, Breton B, Zarzycka B, Han GW, Lu Y, Gati C, Batyuk A, Popov P, Velasquez J et al.. (2019) Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptor. Nat Chem Biol, 15 (1): 11-17. [PMID:30510194]

11. Audoly LP, Ruan X, Wagner VA, Goulet JL, Tilley SL, Koller BH, Coffman TM, Arendshorst WJ. (2001) Role of EP(2) and EP(3) PGE(2) receptors in control of murine renal hemodynamics. Am J Physiol Heart Circ Physiol, 280 (1): H327-33. [PMID:11123248]

12. Audoly LP, Tilley SL, Goulet J, Key M, Nguyen M, Stock JL, McNeish JD, Koller BH, Coffman TM. (1999) Identification of specific EP receptors responsible for the hemodynamic effects of PGE2. Am J Physiol, 277 (3): H924-30. [PMID:10484412]

13. Ayabe S, Murata T, Maruyama T, Hori M, Ozaki H. (2009) Prostaglandin E2 induces contraction of liver myofibroblasts by activating EP3 and FP prostanoid receptors. Br J Pharmacol, 156 (5): 835-45. [PMID:19239477]

14. Badzynska B, Sadowski J. (2008) Opposed effects of prostaglandin E2 on perfusion of rat renal cortex and medulla: interactions with the renin-angiotensin system. Exp Physiol, 93 (12): 1292-302. [PMID:18586855]

15. Bilson HA, Mitchell DL, Ashby B. (2004) Human prostaglandin EP3 receptor isoforms show different agonist-induced internalization patterns. FEBS Lett, 572 (1-3): 271-5. [PMID:15304361]

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