EP3 receptor

Target id: 342

Nomenclature: EP3 receptor

Family: Prostanoid receptors

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Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 390 1p31.2 PTGER3 prostaglandin E receptor 3 2,56-57,59,102,146
Mouse 7 365 3 H4 Ptger3 prostaglandin E receptor 3 (subtype EP3) 117,124
Rat 7 365 2q44-q45 Ptger3 prostaglandin E receptor 3 15,125
Previous and Unofficial Names
PGE receptor EP3 subtype | prostaglandin E receptor 3 | prostanoid EP3 receptor
Database Links
Specialist databases
GPCRDB pe2r3_human (Hs), pe2r3_mouse (Mm), pe2r3_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
PGD2
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

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]PGE2 Rn Full agonist 9.1 pKd 15
pKd 9.1 [15]
PGE2 Mm Full agonist 8.9 pKd 53
pKd 8.9 (Kd 1.4x10-9 M) [53]
[3H]PGE2 Hs Full agonist 8.2 – 9.5 pKd 1,144
pKd 8.2 – 9.5 (Kd 7x10-9 – 3x10-10 M) [1,144]
PGE2 Hs Full agonist 8.2 – 9.1 pKd 116,143-144
pKd 8.7 (Kd 2.1x10-9 M) EP3-II & -III isoforms [116]
pKd 8.2 – 9.1 (Kd 6x10-9 – 8x10-10 M) EP3-I isoform [116,143-144]
PGE2 Rn Full agonist 7.8 – 9.1 pKd 15,86-87,116
pKd 9.0 (Kd 1.1x10-9 M) EP3γ isoform [116]
pKd 8.3 – 9.1 (Kd 5x10-9 – 8x10-10 M) EP3α isoform [15,87,116]
pKd 7.8 – 8.4 (Kd 1.5x10-8 – 3.9x10-9 M) EP3β isoform [86-87]
MB-28767 Hs Full agonist 9.9 pKi 1
pKi 9.9 (Ki 1.4x10-10 M) EP3-III isoform [1]
PGE2 Hs Full agonist 9.5 pKi 1
pKi 9.5 (Ki 3.3x10-10 M) EP3-III isoform [1]
sulprostone Hs Full agonist 9.5 pKi 1
pKi 9.5 (Ki 3.5x10-10 M) EP3-III isoform [1]
sulprostone Mm Full agonist 9.2 pKi 53
pKi 9.2 [53]
MB-28767 Mm Full agonist 9.1 pKi 53
pKi 9.1 (Ki 7x10-10 M) [53]
sulprostone Rn Full agonist 9.1 pKi 15
pKi 9.1 (Ki 7x10-10 M) [15]
PGE2 Mm Full agonist 9.1 pKi 53
pKi 9.1 (Ki 8.5x10-10 M) [53]
PGE1 Mm Full agonist 9.0 pKi 53
pKi 9.0 (Ki 1x10-9 M) [53]
PGE1 Rn Full agonist 9.0 pKi 15
pKi 9.0 (Ki 1x10-9 M) [15]
PGE2 Rn Full agonist 9.0 pKi 15
pKi 9.0 [15]
11-deoxy-PGE1 Mm Partial agonist 8.8 pKi 53
pKi 8.8 (Ki 1.5x10-9 M) [53]
16,16-dimethyl-PGE2 Mm Partial agonist 8.7 pKi 53
pKi 8.7 (Ki 1.9x10-9 M) [53]
GR 63799 Mm Partial agonist 8.7 pKi 53
pKi 8.7 (Ki 1.9x10-9 M) [53]
11-deoxy-PGE1 Rn Full agonist 8.5 pKi 15
pKi 8.5 [15]
ONO-8713 Rn Full agonist 8.5 pKi 15
pKi 8.5 (Ki 3.2x10-9 M) EP3α isoform [15]
17-phenyl-ω-trinor-PGE2 Mm Full agonist 8.4 pKi 53
pKi 8.4 (Ki 3.7x10-9 M) [53]
17-phenyl-ω-trinor-PGE2 Rn Full agonist 8.4 pKi 15
pKi 8.4 (Ki 4.3x10-9 M) EP3α isoform [15]
cloprostenol Hs Full agonist 8.4 pKi 1
pKi 8.4 (Ki 4.4x10-9 M) EP3-III isoform [1]
GR 63799 Hs Agonist 8.3 pKi 1
pKi 8.3 (Ki 4.8x10-9 M) EP3-III isoform [1]
misoprostol (free acid form) Hs Full agonist 8.1 pKi 1
pKi 8.1 (Ki 7.9x10-9 M) EP3-III isoform [1]
ONO-AE-248 Mm Full agonist 7.8 – 8.1 pKi 121,152
pKi 7.8 – 8.1 (Ki 1.5x10-8 – 7.5x10-9 M) EP3α isoform [121,152]
ONO-AP-324 Mm Partial agonist 8.0 pKi 47
pKi 8.0 (Ki 1.1x10-8 M) EP3α isoform [47]
enprostil Hs Full agonist 7.9 pKi 1
pKi 7.9 (Ki 1.2x10-8 M) EP3-III isoform [1]
carbacyclin Hs Full agonist 7.8 pKi 1
pKi 7.8 (Ki 1.4x10-8 M) EP3-III isoform [1]
iloprost Mm Full agonist 7.7 pKi 53
pKi 7.7 (Ki 2.2x10-8 M) [53]
STA2 Mm Full agonist 7.6 pKi 53
pKi 7.6 (Ki 2.3x10-8 M) [53]
carbacyclin Mm Full agonist 7.5 pKi 53
pKi 7.5 (Ki 3.1x10-8 M) [53]
isocarbacyclin Mm Full agonist 7.5 pKi 53
pKi 7.5 (Ki 3.1x10-8 M) [53]
PGF Hs Full agonist 7.4 pKi 1
pKi 7.4 (Ki 3.8x10-8 M) EP3-III isoform [1]
PGD2 Rn Full agonist 5.9 – 8.9 pKi 15
pKi 8.9 (Ki 1.3x10-9 M) EP3α isoform [15]
pKi 5.9 [15]
iloprost Rn Full agonist 7.3 pKi 15
pKi 7.3 (Ki 4.7x10-8 M) EP3α isoform [15]
rivenprost Mm Partial agonist 7.3 pKi 151
pKi 7.3 (Ki 5.6x10-8 M) [151]
GR 63799 Rn Agonist 7.1 pKi 15
pKi 7.1 (Ki 7.3x10-8 M) EP3α isoform [15]
enprostil Rn Full agonist 7.1 pKi 15
pKi 7.1 (Ki 7.4x10-8 M) EP3α isoform [15]
PGF Mm Full agonist 7.1 pKi 53
pKi 7.1 (Ki 7.5x10-8 M) [53]
I-BOP Mm Full agonist 7.0 pKi 53
pKi 7.0 (Ki 1x10-7 M) [53]
iloprost Hs Full agonist 6.7 – 7.3 pKi 1,143
pKi 7.3 (Ki 5.6x10-8 M) EP3-III isoform [1]
pKi 6.7 (Ki 2.08x10-7 M) EP3-I isoform [143]
cicaprost Mm Full agonist 6.8 pKi 53
pKi 6.8 (Ki 1.7x10-7 M) [53]
PGF Rn Full agonist 6.7 pKi 15
pKi 6.7 (Ki 2.13x10-7 M) EP3α isoform [15]
cicaprost Hs Full agonist 6.6 pKi 1
pKi 6.6 (Ki 2.55x10-7 M) EP3-III isoform [1]
PGD2 Mm Full agonist 6.6 pKi 53
pKi 6.6 (Ki 2.8x10-7 M) [53]
misoprostol (methyl ester) Hs Full agonist 6.5 pKi 1
pKi 6.5 (Ki 3.19x10-7 M) EP3-III isoform [1]
beraprost Hs Agonist 6.2 pKi 63
pKi 6.2 (Ki 6.8x10-7 M) [63]
fluprostenol Hs Full agonist 6.2 pKi 1
pKi 6.2 (Ki 7.08x10-7 M) EP3-III isoform [1]
ONO-AE1-329 Mm Full agonist 5.9 pKi 121
pKi 5.9 (Ki 1.2x10-6 M) EP3α isoform [121]
butaprost (free acid form) Hs Full agonist 5.8 pKi 1
pKi 5.8 (Ki 1.643x10-6 M) EP3-III isoform [1]
treprostinil Hs Full agonist 5.6 pKi 143
pKi 5.6 (Ki 2.5x10-6 M) EP3-I isoform [143]
butaprost (free acid form) Rn Full agonist 4.9 pKi 15
pKi 4.9 (Ki 1.18x10-5 M) EP3α isoform [15]
U46619 Hs Full agonist 4.9 pKi 1
pKi 4.9 [1]
U46619 Rn Full agonist 4.8 pKi 15
pKi 4.8 (Ki 1.62x10-5 M) EP3α isoform [15]
SC46275 Cp Full agonist 10.4 pEC50 106
pEC50 10.4 (EC50 4x10-11 M) [106]
PGE2 Rn Full agonist 9.4 pEC50 15
pEC50 9.4 (EC50 4.1x10-10 M) EP3α isoform [15]
sulprostone Rn Full agonist 9.4 pEC50 15
pEC50 9.4 (EC50 4.2x10-10 M) [15]
PGE1 Rn Full agonist 9.4 pEC50 15
pEC50 9.4 (EC50 4.5x10-10 M) EP3α isoform [15]
MB-28767 Rn Full agonist 9.3 pEC50 15
pEC50 9.3 (EC50 5.5x10-10 M) EP3α isoform [15]
iloprost Rn Full agonist 9.2 pEC50 15
pEC50 9.2 (EC50 6.3x10-10 M) EP3α isoform [15]
sulprostone Hs Full agonist 8.9 pEC50 113
pEC50 8.9 (EC50 1.4x10-9 M) [113]
SC46275 Rn Full agonist 8.7 pEC50 39
pEC50 8.7 (EC50 1.8x10-9 M) [39]
enprostil Hs Full agonist 8.4 pEC50 113
pEC50 8.4 (EC50 3.7x10-9 M) [113]
PGF Rn Full agonist 8.4 pEC50 15
pEC50 8.4 (EC50 4.2x10-9 M) EP3α isoform [15]
PGD2 Rn Full agonist 7.9 pEC50 15
pEC50 7.9 (EC50 1.3x10-8 M) EP3α isoform [15]
U46619 Rn Full agonist 6.8 pEC50 15
pEC50 6.8 (EC50 1.49x10-7 M) EP3α isoform [15]
cloprostenol Hs Full agonist 6.7 pEC50 113
pEC50 6.7 (EC50 2.21x10-7 M) [113]
ONO-AE-248 Hs Full agonist 5.6 – 6.7 pEC50 28,69
pEC50 5.6 – 6.7 (EC50 2.3x10-6 – 2x10-7 M) [28,69]
SC46275 Clf Full agonist 11.0 pIC50 134
pIC50 11.0 (IC50 1x10-11 M) [134]
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 [15].

Further potent and selective ligands of the human EP3 receptor have been identified, see [31-32,50].

Sulprostone has been commonly used as an EP3 agonist but shows considerable EP1 agonism [21]; SC46275 [47,106] and ONO-AE-248 [18] 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 [47].

Although M&B28767 is a highly potent EP3 agonist, it also shows significant TP agonism [65]

In the mouse, the three EP3 isoforms show similar ligand binding properties but have different signal transduction properties [119].

Reference [112] uses human platelet preparations instead of transfected cells.

Agonist misoprostol is an effective gastric ulcer therapy [100,104].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
L-826266 Hs Antagonist 8.4 pKB 19
pKB 8.4 (KB 4.5x10-9 M) [19]
ONO-AE3-240 Mm Antagonist 9.6 pKi 4
pKi 9.6 [4]
DG-041 Hs Antagonist 8.4 – 10.1 pKi 49,116
pKi 10.1 (Ki 8x10-11 M) EP3-I isoform [116]
pKi 9.9 (Ki 1.2x10-10 M) EP3-II isoform [116]
pKi 9.5 (Ki 3x10-10 M) EP3-III isoform [116]
pKi 8.4 (Ki 3.9x10-9 M) [49]
L-798,106 Hs Antagonist 7.8 – 9.7 pKi 49-50,116
pKi 7.8 – 9.7 (Ki 1.7x10-8 – 2.1x10-10 M) EP3-III isoform [49-50,116]
L-826266 Hs Antagonist 8.0 – 9.1 pKi 19,48,50
pKi 9.1 (Ki 8x10-10 M) EP3-III isoform (pKi=8.04 in the presence of HSA) [50]
pKi 8.0 – 9.1 (Ki 1.1x10-8 – 8x10-10 M) [19,48]
ONO-AE2-227 Mm Antagonist 7.7 pKi 83
pKi 7.7 (Ki 2.1x10-8 M) [83]
ONO-AE3-208 Mm Antagonist 7.5 pKi 51
pKi 7.5 (Ki 3x10-8 M) [51]
ONO-8711 Mm Antagonist 7.2 pKi 142
pKi 7.2 (Ki 6.7x10-8 M) [142]
SC-51322 Hs Antagonist 6.2 pKi 1
pKi 6.2 (Ki 7x10-7 M) EP3-III isoform [1]
AH6809 Hs Antagonist 5.8 pKi 1
pKi 5.8 (Ki 1.6x10-6 M) EP3-III isoform [1]
ONO-8713 Mm Antagonist <5.0 pKi 142
pKi <5.0 (Ki >1x10-5 M) [142]
ONO-AE5-599 Mm Antagonist 9.7 pIC50 3
pIC50 9.7 (IC50 1.9x10-10 M) [3]
ONO-AE3-240 Mm Antagonist 8.8 pIC50 4
pIC50 8.8 (IC50 1.5x10-9 M) [4]
ONO-AE2-227 Mm Antagonist 6.8 pIC50 83
pIC50 6.8 (IC50 1.6x10-7 M) [83]
View species-specific antagonist tables
Antagonist Comments
Further potent and selective ligands of the human EP3 receptor have been identified, see [31-32,50].

L-796,106 (pA2 = 7.4 - 8.10) [20,39] and ONO-AE3-240 [4,123] are recently developed selective EP3 antagonists.

Care is required in the use of L-826266 and DG-041 owing to their high lipophilicity [48].

Antagonist DG-04, a potential inhibitor of human platelet aggregation, is currently in human clinical trials for the treatment of atherothrombosis [29,114].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  5,88,105,110
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  5,145
Tissue Distribution
Thalamus: anterior, ventromedial, laterodorsal, paraventricular and central medial nuclei.
Species:  Human
Technique:  in situ hybridisation.
References:  120
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:  58
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:  16-17
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:  107
In pregnant myometrium EP3 receptor was only expressed by stromal and endothelial cells.
Species:  Human
Technique:  Western blot, immunohistochemistry.
References:  68
In myometrium EP3 receptor expression is increased in placenta, chorion and amnion with labour.
Species:  Human
Technique:  in situ hybridization., immunohistochemistry.
References:  138
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:  67
Kidney and uterus.
Species:  Human
Technique:  RT-PCR.
References:  5
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:  80
Mouth: gingival fibroblasts.
Species:  Human
Technique:  RT-PCR.
References:  90
Kidney: cortical and outer medullary collecting duct, medullary thick ascending limb.
Species:  Human
Technique:  in situ hybridization.
References:  17
Eye: corneal endothelium and keratocytes, trabecular cells, ciliary epithelium, conjunctival and iridal stroma cells, retinal Muller cells.
Species:  Human
Technique:  Immunohistochemistry.
References:  107
In intestinal mucosa, EP3 receptors are expressed on epithelia at the apex of crypts.
Species:  Human
Technique:  in situ hybridization, immunohistochemistry.
References:  122
Myometrium.
Species:  Human
Technique:  Northern blotting.
References:  73
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:  140
Aorta.
Species:  Mouse
Technique:  RNase protection assay.
References:  153
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:  120
Kidney: tubules in the outer medulla and in the distal tubules in the cortex.
Species:  Mouse
Technique:  in situ hybridization.
References:  118
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:  81
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:  81
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:  118-119
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:  37
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:  22
Kidney: outer medulla > cortex > papilla.
Species:  Rat
Technique:  RNase protection assay.
References:  44
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:  82,84
Tissue Distribution Comments
Prostanoid receptor antibodies, are not very selective for immunochemistry experiments, results with other experimental approaches in parallel are necessary.
Expression Datasets

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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
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:  117
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:  132
EP3-I isoform stimulation, cAMP dependent mechanism.
Species:  Human
Tissue:  CHO cells.
Response measured:  Acid extrusion.
References:  97
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:  43
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:  14
EP3 mediated inhibition of CaV2 voltage-gated Ca2+ channel currents (ICa)
Species:  Mouse
Tissue:  Adrenal chromaffin cells.
Response measured: 
References:  45
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:  86
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:  128
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:  40-41,85
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:  87
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:  12
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:  15
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
Airway constriction.
Species:  Mouse
Tissue:  In vivo.
References:  133
Constriction of venules.
Species:  Rat
Tissue:  Stomach.
References:  93
Blood pressure regulation (male only).
Species:  Mouse
Tissue:  In vivo.
References:  11
Renal vasoconstriction.
Species:  Mouse
Tissue:  In vivo.
References:  111
Duodenal HCO3- secretion.
Species:  Rat
Tissue:  Duodenum.
References:  131
Mechanical hyperalgesia.
Species:  Rat
Tissue:  In vivo.
References:  95
Inhibition of gastric acid secretion.
Species:  Rat
Tissue:  In vivo (stomach).
References:  52
Inhibition of lipolysis.
Species:  Rat
Tissue:  Isolated adipocytes.
References:  115
Inhibition of noradrenaline release.
Species:  Rat
Tissue:  Isolated trachea.
References:  101
Inhibition of a neurogenic vasopressor response.
Species:  Rat
Tissue:  In vivo.
References:  72
Thermal hyperalgesia.
Species:  Rat
Tissue:  In vivo.
References:  38,94
Stimulation of noradrenaline release.
Species:  Rat
Tissue:  In vivo.
References:  148-149
Inhibition of gastric noradrenaline release.
Species:  Rat
Tissue:  Isolated stomach.
References:  147
Inhibition of vagally mediated gastric acid secretion.
Species:  Rat
Tissue:  In vivo.
References:  150
Inhibition of acetylcholine release.
Species:  Human
Tissue:  Isolated bronchi.
References:  103
Thermal hyperalgesia.
Species:  Mouse
Tissue:  In vivo.
References:  77
Intestinal protection.
Species:  Rat
Tissue:  In vivo (intestine).
References:  60-61
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:  34
Nitric oxide (NO) release via Rho-kinase activation.
Species:  Mouse
Tissue:  Spinal cord slices.
References:  74
Vasoconstriction.
Species:  Rat
Tissue:  Mesenteric artery.
References:  54
PGE2 inhibits monoamine release via presynaptic EP(3) receptors.
Species:  Mouse
Tissue:  Hippocampus, cortex.
References:  24,35
PGE2 inhibits monoamine release via presynaptic EP(3) receptors.
Species:  Rat
Tissue:  Cortex, vas deferens, trachea, stomach.
References:  24,35,101,147
PGE2 suppresses allergic inflammation by activation of the EP3 receptor.
Species:  Mouse
Tissue:  Lung.
References:  62
PGE2 induces fever via the EP3 receptor.
Species:  Mouse
Tissue:  Preoptic hypothalamus.
References:  30,36
PGE2-induced decrease in acid secretion via EP3 receptor.
Species:  Mouse
Tissue:  Stomach.
References:  89
Vasoconstriction.
Species:  Human
Tissue:  Pulmonary artery, intercostal artery, mammary artery.
References:  28,69,91,99
PGE2-induced depolarization of sensory nerves.
Species:  Human
Tissue:  Vagus nerves.
References:  71
PGE2 involvement in atherothrombosis +/- effect of EP3 antagonists.
Species:  Human
Tissue:  Platelet aggregation.
References:  29,109,114
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:  71
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:  64
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:  13
Reduction in infarct size.
Species:  Rat
Tissue:  Myocardium.
References:  152
PGE2 inhibits monoamine release via presynaptic EP(3) receptors.
Species:  Human
Tissue:  Atrial, saphenous vein, pulmonary artery.
References:  78-79
PGE2-to-EP3 signaling pathway is mediated mainly by the EP3γ isoform in the motor neurons of mice.
Species:  Mouse
Tissue:  Motor neurons
References:  55
Physiological Consequences of Altering Gene Expression
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:  133
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:  10
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:  60-61
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:  34
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:  141
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:  92
EP3 receptor knockout mice exhibit reduced inflammatory nociception.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  136
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
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:  70
EP3 knockout mice display enhanced allergic asthma when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  62
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:  126,129-130
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:  77
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:  42
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:  135
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:  25,33
PGE2 induced depolarization of sensory nerves are virtually abolished in EP3-deficient mice.
Species:  Mouse
Tissue:  Vagus nerves.
Technique:  Gene knockouts.
References:  71
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:  75
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:  36
Abnormal urine osmolality in EP3 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  26
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:  66,96,139
Decreased renal vascular resistance in EP3 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  10
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:  76
Phenotypes, Alleles and Disease Models 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
Disease:  Stevens-Johnson syndrome
Synonyms: Severe cutaneous adverse reaction, susceptibility to [OMIM: 608579]
Disease Ontology: DOID:0050426
OMIM: 608579
Orphanet: ORPHA36426
Comments: 
References:  137