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IP receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 345

Nomenclature: IP 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 7 386 19q13.32 PTGIR prostaglandin I2 receptor 9,49
Mouse 7 415 7 9.15 cM Ptgir prostaglandin I receptor (IP) 51
Rat 7 416 1q21 Ptgir prostaglandin I2 receptor 59
Previous and Unofficial Names Click here for help
prostanoid IP receptor | prostacyclin receptor | prostaglandin I2 receptor | prostaglandin I2 (prostacyclin) receptor (IP)
Database Links Click here for help
Specialist databases
GPCRdb pi2r_human (Hs), pi2r_mouse (Mm), pi2r_rat (Rn)
Other databases
Alphafold P43119 (Hs), P43252 (Mm), P43253 (Rn)
ChEMBL Target CHEMBL1995 (Hs), CHEMBL3322 (Rn)
DrugBank Target P43119 (Hs)
Ensembl Gene ENSG00000160013 (Hs), ENSMUSG00000043017 (Mm), ENSRNOG00000016756 (Rn)
Entrez Gene 5739 (Hs), 19222 (Mm), 292661 (Rn)
Human Protein Atlas ENSG00000160013 (Hs)
KEGG Gene hsa:5739 (Hs), mmu:19222 (Mm), rno:292661 (Rn)
OMIM 600022 (Hs)
Pharos P43119 (Hs)
RefSeq Nucleotide NM_000960 (Hs), NM_008967 (Mm), NM_001077644 (Rn)
RefSeq Protein NP_000951 (Hs), NP_032993 (Mm), NP_001071112 (Rn)
UniProtKB P43119 (Hs), P43252 (Mm), P43253 (Rn)
Wikipedia PTGIR (Hs)
Natural/Endogenous Ligands Click here for help
PGD2
PGE1
PGE2
PGF2α
PGI2
Comments: PGI2 is the principal endogenous agonist
Potency order of endogenous ligands
PGI2 >> PGE1 > PGD2, PGF2α > 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
taprostene Small molecule or natural product Hs Partial agonist 9.1 pKd 76
⤷ pKd 9.1 (Kd 7.69x10-10 M) [76]
[3H]iloprost Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Full agonist 8.9 pKd 59
⤷ pKd 8.9 [59]
[3H]iloprost Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 7.7 – 9.0 pKd 1,9,76-77
⤷ pKd 7.7 – 9.0 (Kd 2x10-8 – 1x10-9 M) [1,9,76-77]
[3H]iloprost Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Full agonist 8.3 pKd 51
⤷ pKd 8.3 [51]
esuberaprost Small molecule or natural product Primary target of this compound Hs Agonist 7.9 pKd 34
⤷ pKd 7.9 (Kd 1.3x10-8 M) [34]
FK-788 Small molecule or natural product Hs Full agonist 8.1 pKi 23
⤷ pKi 8.1 [23]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 8.0 pKi 36
⤷ pKi 8.0 [36]
cicaprost Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 8.0 pKi 36
⤷ pKi 8.0 [36]
PGI2 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 7.8 pKi 62
⤷ pKi 7.8 (Ki 1.585x10-8 M) [62]
cicaprost Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 7.8 pKi 1
⤷ pKi 7.8 [1]
isocarbacyclin Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.8 pKi 36
⤷ pKi 7.8 [36]
beraprost Small molecule or natural product Mm Full agonist 7.8 pKi 36
⤷ pKi 7.8 [36]
iloprost Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 7.5 – 8.0 pKi 1,77
⤷ pKi 7.5 – 8.0 [1,77]
beraprost Small molecule or natural product Rn Agonist 7.7 pKi 39
⤷ pKi 7.7 (Ki 1.9x10-8 M) [39]
MRE-269 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.7 pKi 6,39
⤷ pKi 7.7 (Ki 2x10-8 M) [6,39]
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 7.5 pKi 36
⤷ pKi 7.5 [36]
treprostinil Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.5 pKi 76
⤷ pKi 7.5 [76]
beraprost Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.4 pKi 39
⤷ pKi 7.4 (Ki 3.9x10-8 M) [39]
ONO-1301 Small molecule or natural product Mm Full agonist 7.3 pKi 36
⤷ pKi 7.3 [36]
FR181157 Small molecule or natural product Hs Full agonist 7.3 pKi 68
⤷ pKi 7.3 [68]
carbacyclin Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.0 pKi 36
⤷ pKi 7.0 [36]
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 Hs Full agonist 6.5 – 6.8 pKi 42,64
⤷ pKi 6.5 – 6.8 (Ki 3.18x10-7 – 1.5x10-7 M) [42,64]
MRE-269 Small molecule or natural product Ligand has a PDB structure Rn Full agonist 6.7 pKi 39
⤷ pKi 6.7 (Ki 2.2x10-7 M) [39]
selexipag Small molecule or natural product Approved drug Hs Agonist 6.6 pKi 39
⤷ pKi 6.6 (Ki 2.6x10-7 M) [39]
carbacyclin Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.5 – 6.6 pKi 1
⤷ pKi 6.5 – 6.6 [1]
selexipag Small molecule or natural product Approved drug Rn Agonist 5.7 pKi 39
⤷ pKi 5.7 (Ki 2.1x10-6 M) [39]
butaprost (free acid form) Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.3 pKi 1
⤷ pKi 4.3 [1]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 4.2 pKi 1
⤷ pKi 4.2 [1]
treprostinil Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.7 pEC50 74,76
⤷ pEC50 8.7 [74,76]
AFP-07 Small molecule or natural product Hs Full agonist 8.5 pIC50 12
⤷ pIC50 8.5 (IC50 3.16x10-9 M) [12]
TEI-9063 Small molecule or natural product Hs Full agonist 8.5 pIC50 31
⤷ pIC50 8.5 [31]
BMY 45778 Small molecule or natural product Hs Full agonist 8.0 pIC50 31
⤷ pIC50 8.0 (IC50 1x10-8 M) [31]
taprostene Small molecule or natural product Hs Full agonist 6.9 pIC50 31
⤷ pIC50 6.9 [31]
EP 157 Small molecule or natural product Hs Full agonist 4.9 – 5.7 pIC50 3
⤷ pIC50 4.9 – 5.7 (IC50 1.12x10-5 – 2.03x10-6 M) [3]
View species-specific agonist tables
Agonist Comments
References [12,31] use human platelet preparations instead of transfected cells.

Stable analogues of prostacyclin (e.g. iloprost, carbacyclin, AFP-07) often show potent EP1 agonist and modest EP3 agonism; cicaprost is the most selective IP agonist [15,40]. Treprostinil has high affinity for the DP1 and EP2 receptors with pKi values of 8.36 and 8.44 respectively [76]. IP receptor agonism is generated by the introduction of a diaryl-heteroatomic unit into PGH analogues (e.g. EP-157) and other n-alkylcarboxylic acids (BMY-45778, ONO-1301, MRE-269) often designated as 'non-prostanoid prostacyclin mimetics' [32,43]. MRE 269 is the biologically-active metabolite of the pro-drug, NS304 (ACT-293987) which has the INN selexipag.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CAY10441 Small molecule or natural product Hs Antagonist 8.2 – 9.0 pA2 8,52
⤷ pA2 8.2 – 9.0 [8,52]
RO3244794 Small molecule or natural product Hs Antagonist 8.5 pA2 8
⤷ pA2 8.5 [8]
RO3244794 Small molecule or natural product Hs Antagonist 9.1 – 9.5 pKB 80-81
⤷ pKB 9.1 – 9.5 [80-81]
TG6-129 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.7 pKB 18
⤷ pKB 6.7 (KB 1.99x10-7 M) [18]
CAY10441 Small molecule or natural product Hs Antagonist 8.7 pKi 8
⤷ pKi 8.7 [8]
RO3244794 Small molecule or natural product Hs Antagonist 6.9 pKi 8
⤷ pKi 6.9 [8]
BAY-73-1449 Small molecule or natural product Hs Antagonist >10.0 pIC50 7
⤷ pIC50 >10.0 (IC50 <1x10-10 M) [7]
Antagonist Comments
RO-1138452 has similar pA2 values (8.1 - 8.4) for human, guinea-pig and rabbit IP receptors [33]. However, it also has moderately high affinity for imidazoline I2 and PAF receptors [8]. RO-3244794 appears to be more specific [8]. RO-1138452 may behave as a pseudo-irreversible antagonist [5,52].
Allosteric Modulator Comments
A positive modulator for the human IP receptor has been reported (the [R] enantiomer of 1,2,3,4-tetrahydroisoquinoline derivative IPPAM-1) [83].
Immunopharmacology Comments
Although primarily recognised for vasodilatory and antihypertensive action in pulmonary arterial hypertension (PAH) the importance of PGI2 as an immunomodulatory agent has been investigated more recently. PGI2 regulates both the innate and adaptive immune systems and its effects are thought to be mainly anti-inflammatory or immunosuppressive, which may have implications for clinical use. Note also that the prostacyclin analog, cicaprost, exhibits potent anti-inflammatory activity in human primary immune cells [72]. Papers have appeared on immune responses modulation by PGI2 via IP signaling [87], as well on PGI2 promoting in vivo Th17 differentiation, with possible clinical implications for the use of PGI2 and its analogs in PAH treatment [86].
Immuno Process Associations
Immuno Process:  Inflammation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  51,60
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
Gq/G11 family 		Adenylyl cyclase inhibition
Phospholipase C stimulation
Comments:  Gq signalling has been reported in heterologous expression systems but it is unclear whether this coupling occurs widely in native cells or tissues [44].
References:  44,60
Tissue Distribution Click here for help
Airway smooth muscle cells.
Species:  Human
Technique:  RT-PCR.
References:  14
Basophils.
Species:  Human
Technique:  Radioligand binding.
References:  70
Aorta, lung, atrium, ventricle, kidney.
Species:  Human
Technique:  Northern blotting.
References:  49
Kidney > lung, liver > skeletal muscle, heart.
Species:  Human
Technique:  Northern blotting.
References:  9
Thymus > spleen > heart > lung.
Species:  Mouse
Technique:  Northern blotting.
References:  51
Kidney: medullary thick ascending limb.
Species:  Rat
Technique:  In situ hybridisation and RT-PCR.
References:  27
CNS: dorsal root ganglion neurons.
Species:  Rat
Technique:  RT-PCR.
References:  47
Expression Datasets Click here for help

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

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Functional Assays Click here for help
Measurement of cAMP levels in CHO cells transfected with the mouse IP receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  Stimulation of cAMP accumulation.
References:  51
Measurement of PI metabolite formation in CHO cells transfected with the mouse IP receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  Stimulation of PI hydrolysis.
References:  51
Measurement of cAMP levels in adult rat cardiomyocytes endogenously expressing the IP receptor.
Species:  Rat
Tissue:  Cardiomyocytes.
Response measured:  Stimulation of cAMP accumulation.
References:  57
Measurement of cAMP and substance P levels in cultured rat dorsal root ganglion neurons endogenously expressing the IP receptor.
Species:  Rat
Tissue:  Cultured dorsal root ganglion neurons.
Response measured:  Stimulation of cAMP accumulation and substance P release.
References:  47
Measurement of cAMP levels in Xenopus oocytes transfected with the human IP receptor and the cystic fibrosis transmembrane conductance regulator (a cAMP-activated Cl- channel).
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Stimulation of cAMP accumulation.
References:  9,20
Measurement of cAMP levels in human platelets endogenously expressing the IP receptor.
Species:  Human
Tissue:  Platelets.
Response measured:  Stimulation of cAMP accumulation.
References:  61
Measurement of cAMP levels in HEL cells endogenously expressing the IP receptor.
Species:  Human
Tissue:  HEL cells.
Response measured:  Stimulation of cAMP accumulation.
References:  16
Measurement of Ca2+ levels in human erythroleukemia (HEL) cells endogenously expressing the IP receptor.
Species:  Human
Tissue:  HEL cells.
Response measured:  Increase in Ca2+ concentration.
References:  16
Measurement of CRE-dependent transcription and augmentation of GRE-dependent transcription in cells endogenously expressing the IP receptor
Species:  Human
Tissue:  BEAS-2B airway epithelial cells.
Response measured:  Activation of CRE and GRE luciferase reporter constructs.
References:  5,80-81
Measurement of cAMP in dorsal root ganglion neurons and UMR 108 cells endogenously expressing the IP receptor.
Species:  Rat
Tissue:  Dorsal root ganglion neurons and UMR 108 osteosarcoma cells.
Response measured:  Stimulation of cAMP accumulation.
References:  48
Measurement of cAMP levels in HEK-293 cells transfected with the human IP receptor. This study directly compares iloprost and treprostinil binding.
Species:  Human
Tissue:  HEK-293 cells transfected with the human IP receptor.
Response measured:  Stimulation of cAMP accumulation.
References:  76
Measurement of cAMP levels in COS-7 cells transfected with the human IP receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  49
Physiological Functions Click here for help
Inhibition of platelet aggregation.
Species:  Human
Tissue:  Platelets.
References:  4,61
Inhibition of platelet aggregation.
Species:  Rat
Tissue:  Platelets.
References:  4,61
Antihypertrophy.
Species:  Rat
Tissue:  Cardiomyocytes.
References:  57
Relaxation of bronchial smooth muscle.
Species:  Human
Tissue:  Bronchial preparations.
References:  24,53
Augmentation of glucocorticoid-induced gene expression
Species:  Human
Tissue:  Airway epithelial cells.
References:  81
Inhibition of chemokine release.
Species:  Human
Tissue:  Airway epithelial cells.
References:  5
Sensitisation of sensory neurons.
Species:  Rat
Tissue:  Dorsal root ganglion neurons.
References:  48
Inhibition of chemokine/cytokine release.
Species:  Mouse
Tissue:  Th1 and Th2 cells.
References:  85
Relaxation of pulmonary and venous arterial smooth muscle.
Species:  Human
Tissue:  Pulmonary vascular preparations.
References:  6,24,71
Relaxation of rat pulmonary smooth muscle.
Species:  Rat
Tissue:  Pulmonary arterial and venous preparations.
References:  54
Physiological Consequences of Altering Gene Expression Click here for help
IP receptor knockout mice exhibit reduced inflammatory and pain responses and increased susceptibility to thrombosis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  45
IP receptor knockout mice exhibit reduced inflammatory nociception.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  69
IP receptor knockout mice exhibit increased cardiomyocyte and cardiac hypertrophy and increased cardiac fibrosis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  21
IP receptor knockout mice exhibit increased allergic inflammation in airways and skin, as well as increased capillary pemeability and increased IgE and IgG production.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  66
IP knockout mice exhibit enhanced atherogenesis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
Injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the IP receptor.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
Cardiac injury upon post-ischemic reperfusion was worsened in mice lacking the IP receptor.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  82
IP knockout mice develop more severe pulmonary hypertension and vascular remodeling after chronic hypoxic exposure, when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  26
IP1 receptor deficient mice exhibited significant reduction in arthritis scores compared to wild-type mice.
Species:  Mouse
Tissue:  Knee joint.
Technique:  Gene targeting in embryonic stem cells.
References:  25
In sensitized mice, prolonged allergen exposure increases pulmonary eosinophil and lymphocyte burden, Th2 cytokines and ovalbumin-specific immunoglobulin IgE and IgG1 in serum that is significantly enhanced in animals lacking the IP1 receptor.
Species:  Mouse
Tissue:  Lung and T-lymphocytes
Technique:  Gene targeting in embryonic stem cells.
References:  46
IP-deficient mice are more susceptible to respiratory syncytial virus-induced illness.
Species:  Mouse
Tissue:  Respiratory tract.
Technique:  Gene targeting in embryonic stem cells.
References:  22
Th1 cell differentiation in a model of contact hypersensitivity is inhibited in IP receptor knockout mice.
Species:  Mouse
Tissue:  T-lymphocytes.
Technique:  Gene targeting in embryonic stem cells.
References:  50
IP receptor-deficient mice have impaired Th17 differentiation and delayed onset of experimental autoimmune encephalomyelitis.
Species:  Mouse
Tissue:  Th17 T-lymphocytes and CNS.
Technique:  Gene targeting in embryonic stem cells.
References:  86
IP receptor deficiency inhibits recruitment of endothelial progenitor cells and accelerates vascular remodelling in wire injury-mediated neointimal hyperplasia.
Species:  Mouse
Tissue:  Endothelial progenitor cells and femoral artery.
Technique:  Gene targeting in embryonic stem cells.
References:  35
IP receptor-deficient mice develop salt-sensitive hypertension, cardiac hypertrophy, and cardiac fibrosis.
Species:  Mouse
Tissue:  Myocardium, vascular smooth muscle.
Technique:  Gene targeting in embryonic stem cells.
References:  11,17
IP receptor inactivation promotes anatomical and functional damage following ischemic stroke.
Species:  Mouse
Tissue:  Middle cerebral artery.
Technique:  Gene targeting in embryonic stem cells.
References:  58
IP receptor deletion aggravates hippocampal neuronal loss after bilateral common carotid artery occlusion.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene targeting in embryonic stem cells.
References:  75
IP receptor deletion inhibits the development of IL-17-producing γδ T cells.
Species:  Mouse
Tissue:  Thymus and lungs during allergic inflammation.
Technique:  Gene targeting in embryonic stem cells.
References:  30
IP receptor deletion attenuates zymosan-induced pleurisy.
Species:  Mouse
Tissue:  Pleural cavity.
Technique:  Gene targeting in embryonic stem cells.
References:  84
CCL17-induced chemotaxis of CD4+ Th2 T-cells is unaffected in cells harvested from IP receptor deficient mice compared to wild type mice.
Species:  Mouse
Tissue:  CD4+ Th2 T-cells.
Technique:  Gene targeting in embryonic stem cells.
References:  29
Neuronal cell loss after brain trauma is enhanced in IP receptor deficient mice compared to wild type animals.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene targeting in embryonic stem cells.
References:  41
Migration and cell fusion are attenuated in myoblasts harvested from IP receptor-deficient mice compared to wild type animals.
Species:  Mouse
Tissue:  Skeletal muscle.
Technique:  Gene targeting in embryonic stem cells.
References:  10
Ischemia/reperfusion-induced gastric lesions are aggravated in IP receptor-deficient mice.
Species:  Mouse
Tissue:  Stomach.
Technique:  Gene targeting in embryonic stem cells.
References:  38
Mice deficient in the IP receptor are protected against experimental osteoarthritis and rheumatoid arthritis
Species:  Mouse
Tissue:  Knee joint.
Technique:  Gene targeting in embryonic stem cells.
References:  56
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
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0002551 abnormal blood coagulation PMID: 9262402 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0000249 abnormal blood vessel physiology PMID: 11964481 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0001544 abnormal cardiovascular system physiology PMID: 11964481 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0005464 abnormal platelet physiology PMID: 11964481 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0009818 abnormal thromboxane level PMID: 11964481 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0005087 decreased acute inflammation PMID: 9262402 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0009815 decreased prostaglandin level PMID: 9262402 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0008531 increased chemical nociceptive threshold PMID: 9262402 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0002080 prenatal lethality PMID: 9262402 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0005048 thrombosis PMID: 16614756  9262402 
Ptgirtm1Sna Ptgirtm1Sna/Ptgirtm1Sna
involves: 129P2/OlaHsd * C57BL/6		 MGI:99535  MP:0005413 vascular restenosis PMID: 11964481 
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphisms
Species:  Human
Description:  Coronary artery occlusion.
References:  63
Type:  Single nucleotide polymorphisms
Species:  Human
Description:  R212C; enhances cardiovascular disease progression if risk factors co-exist.
References:  2,55
Type:  Single nucleotide polymorphisms
Species:  Human
Description:  IP1 variants including R77C, L104R, M113T, R212H, R212C, R215C, R279C, I293N have impaired cAMP signalling.
References:  63,65
General Comments
Human IP forms homo-oligomers via disulfide bonds, which might be essential for receptor trafficking to the cell surface [19]. The IP receptor was the first to be described to form heterodimers, most interestingly with its physiologic opponent, the TP receptor, leading to unexpected TP-mediated cAMP formation [28,78-79].

Pharmacological evidence for a second IP receptor, denoted IP2, in the central nervous system [67,73] and in the BEAS-2B human airway epithelial cell line [80] is available. This receptor is selectively activated by 15R-17,18,19,20-tetranor-16-m-tolyl-isocarbacyclin (15R-TIC) and 15R-Deoxy 17,18,19,20-tetranor-16-m-tolyl-isocarbacyclin (15-deoxy-TIC). However, molecular biological evidence for the IP2 subtype is currently lacking.

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. Arehart E, Stitham J, Asselbergs FW, Douville K, MacKenzie T, Fetalvero KM, Gleim S, Kasza Z, Rao Y, Martel L et al.. (2008) Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circ Res, 102 (8): 986-93. [PMID:18323528]

3. Armstrong RA, Jones RL, MacDermot J, Wilson NH. (1986) Prostaglandin endoperoxide analogues which are both thromboxane receptor antagonists and prostacyclin mimetics. Br J Pharmacol, 87 (3): 543-51. [PMID:3026540]

4. Armstrong RA, Lawrence RA, Jones RL, Wilson NH, Collier A. (1989) Functional and ligand binding studies suggest heterogeneity of platelet prostacyclin receptors. Br J Pharmacol, 97: 657-668. [PMID:2474350]

5. Ayer LM, Wilson SM, Traves SL, Proud D, Giembycz MA. (2008) 4,5-Dihydro-1H-imidazol-2-yl)-[4-(4-isopropoxy-benzyl)-phenyl]-amine (RO1138452) is a selective, pseudo-irreversible orthosteric antagonist at the prostacyclin (IP)-receptor expressed by human airway epithelial cells: IP-receptor-mediated inhibition of CXCL9 and CXCL10 release. J Pharmacol Exp Ther, 324 (2): 815-26. [PMID:17962517]

6. Benyahia C, Boukais K, Gomez I, Silverstein A, Clapp L, Fabre A, Danel C, Leséche G, Longrois D, Norel X. (2013) A comparative study of PGI2 mimetics used clinically on the vasorelaxation of human pulmonary arteries and veins, role of the DP-receptor. Prostaglandins Other Lipid Mediat, 107: 48-55. [PMID:23850788]

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