Gene and Protein Information
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	2,56-57,59,102,146
Mouse	7	365	3 81.32 cM	Ptger3	prostaglandin E receptor 3 (subtype EP3)	117,124
Rat	7	365	2q45	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	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_198717 (Hs), NM_198718 (Hs), NM_198719 (Hs), NR_028294 (Hs), NR_028293 (Hs), NM_198715 (Hs), NM_001126044 (Hs), NM_198714 (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)

Natural/Endogenous Ligands
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

Agonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter 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] PGF2α 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] PGF2α 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] PGF2α 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] PGF2α 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 Value Parameter 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].

Immunopharmacology Comments

Foudi et al. (2012) [27] 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
Transducer	Effector/Response
Gi/Go family	Adenylyl cyclase inhibition
References:  5,88,105,110

Secondary Transduction Mechanisms
Transducer	Effector/Response
Gq/G11 family	Phospholipase C stimulation
References:  5,145

Tissue Distribution
In intestinal mucosa, EP3 receptors are expressed on epithelia at the apex of crypts. Species:  Human Technique:  in situ hybridization, immunohistochemistry. References:  122
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
Mouth: gingival fibroblasts. Species:  Human Technique:  RT-PCR. References:  90
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
Myometrium. Species:  Human Technique:  Northern blotting. References:  73
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
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:  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:  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
Show »« Hide 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] There should be a chart of expression data here, you may need to enable JavaScript!

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
PGE2-induced decrease in acid secretion via EP3 receptor. Species:  Mouse Tissue:  Stomach. References:  89
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
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
Vasoconstriction. Species:  Rat Tissue:  Mesenteric artery. References:  54
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
Abnormal urine osmolality in EP3 knockout mice. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  26
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:  60-6