S1P<sub>3</sub> receptor | Lysophospholipid (S1P) receptors | IUPHAR/BPS Guide to PHARMACOLOGY

S1P3 receptor

Target id: 277

Nomenclature: S1P3 receptor

Family: Lysophospholipid (S1P) receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     S1P3 receptor has curated GtoImmuPdb data

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 378 9q22.1-q22.2 S1PR3 sphingosine-1-phosphate receptor 3
Mouse 7 378 13 B1 S1pr3 sphingosine-1-phosphate receptor 3
Rat 7 379 17 p14 S1pr3 sphingosine-1-phosphate receptor 3
Previous and Unofficial Names
edg3 | endothelial differentiation G protein-coupled receptor 3
Database Links
Specialist databases
GPCRDB s1pr3_human (Hs), s1pr3_mouse (Mm)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
sphingosine 1-phosphate
sphingosylphosphorylcholine
Comments: Sphingosine 1-phosphate exhibits greater potency than sphingosylphosphorylcholine
Potency order of endogenous ligands
sphingosine 1-phosphate > dihydrosphingosine 1-phosphate > sphingosylphosphorylcholine  [28]

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
sphingosine 1-phosphate Hs Agonist 7.6 – 9.6 pKd 12,22,37
pKd 7.6 – 9.6 (Kd 2.62x10-8 – 2.3x10-10 M) [12,22,37]
sphingosine 1-phosphate Hs Agonist 8.4 – 9.8 pEC50 8,19,31
pEC50 8.4 – 9.8 [8,19,31]
sphingosine 1-phosphate Mm Agonist 8.6 pEC50 33
pEC50 8.6 (EC50 2.3x10-9 M) [33]
FTY720-phosphate Hs Agonist 7.8 – 9.4 pEC50 8,14
pEC50 7.8 – 9.4 [8,14]
AFD(R) Hs Agonist 7.8 – 9.4 pEC50 8
pEC50 7.8 – 9.4 [8]
(S)-FTY720-phosphate Hs Agonist 8.5 pEC50 31
pEC50 8.5 (EC50 3.1x10-9 M) [31]
VPC12249 Hs Agonist 6.5 pEC50 15
pEC50 6.5 [15]
ASP4058 Hs Agonist 6.0 pEC50 40
pEC50 6.0 (EC50 9.2x10-7 M) [40]
Description: In a GTPγS binding assay.
AUY954 Mm Agonist 5.9 – 6.0 pEC50 15,31
pEC50 5.9 – 6.0 [15,31]
siponimod Hs Agonist 5.3 pEC50 30
pEC50 5.3 (EC50 5x10-6 M) [30]
Description: In a GTPγS binding assay
compound 43 [PMID: 26751273] Hs Agonist 5.1 pEC50 11
pEC50 5.1 (EC50 7.943x10-6 M) [11]
Description: In a GTPγS assay.
ozanimod Hs Agonist <5.0 pEC50 35
pEC50 <5.0 (EC50 >1x10-5 M) [35]
Description: In a GTPγS assay.
FTY720-phosphate Hs Agonist 8.3 pIC50 14
pIC50 8.3 (IC50 5x10-9 M) [14]
ponesimod Hs Agonist 5.7 pIC50 7
pIC50 5.7 (IC50 2.068x10-6 M) [7]
Description: In a radioligand binding assay using membranes from CHO cells expressing human S1P2
compound 26 [PMID: 16190743] Hs Agonist 4.9 pIC50 24
pIC50 4.9 [24]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
SPM-354 Hs Antagonist 9.3 pA2 34
pA2 9.3 [34]
Description: In a β-arrestin assay.
VPC03090-P Hs Antagonist 7.2 – 7.3 pKi 21
pKi 7.2 – 7.3 (Ki 5.87x10-8 – 5.1x10-8 M) [21]
VPC44116 Hs Antagonist 6.5 pKi 15
pKi 6.5 (Ki 3x10-7 M) [15]
VPC23019 Hs Antagonist 5.9 pKi 10
pKi 5.9 [10]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CYM-5541 Hs Positive 8.5 pA2 34
pA2 8.5 [34]
Description: In a β-arrestin assay.
Immunopharmacology Comments
In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment:  Eosinophils express all S1P receptors except S1P2R.
References:  18
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001816 cytokine production IEA
GO:0032651 regulation of interleukin-1 beta production IEA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family
Adenylate cyclase inhibition
Phospholipase C stimulation
Comments:  Activation of MAPK [29] and Akt [5-6].
References:  2,39
Tissue Distribution
Heart, lung, kidney, spleen, brain, thymus, muscle and testis
Species:  Mouse
Technique:  Northern blot
References:  41-42
Embryonic brain
Species:  Mouse
Technique:  in situ hybridisation
References:  20
Expression Datasets

Show »

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
Migration
Species:  Mouse
Tissue:  B cell, monocytes
Response measured: 
References:  3,9,13
Cell proliferation and survival
Species:  Human
Tissue:  HTC4 hepatoma cells stably transfected with human S1P3
Response measured: 
References:  1
Exocytosis
Species:  Rat
Tissue:  Hippocampal neurons inhibitted by CAY1044 and siRNA.
Response measured:  Distribution of Synapsin I.
References:  32
Physiological Consequences of Altering Gene Expression
Migration deficit of anti-inflammatory monocytes in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  3
B-cell migration and development
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  13
No obvious phenotypic abnormalities, but severe vascular phenotype in S1P2/S1P3 double and S1P1/S1P2/S1P3 triple knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  23
No obvious phenotypic abnormalities
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  20
Protection from heart ischemia/reperfusion injury in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  25,36
Protection from kidney ischemia/reperfusion injury in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  4
Eyelid closure during embryonic development in S1P2/S1P3 double knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  16
Blockade of HDL-induced vasorelaxation in knockout mice
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  26
Hematopoietic stem and progenitor cell migration.
Species:  Mouse
Tissue:  Bone marrow
Technique:  Gene knockouts
References:  27
Cardioprotection via RhoA activation.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockouts
References:  27
Impaired working memory and hippocampal neuron excitability.
Species:  Mouse
Tissue:  Hippocampal neurons.
Technique:  Gene knockouts
References:  38
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
S1pr1tm1Rlp|S1pr2tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MGI:99569  MP:0000260 abnormal angiogenesis PMID: 15138255 
S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MP:0002459 abnormal B cell physiology PMID: 15184895 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MP:0005621 abnormal cell physiology PMID: 11443127 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ
MGI:1339365  MP:0008713 abnormal cytokine level PMID: 18305483 
S1pr1tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MP:0002109 abnormal limb morphology PMID: 15138255 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0001386 abnormal maternal nurturing PMID: 12006579 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0001504 abnormal posture PMID: 17287522 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MP:0002273 abnormal respiratory alveolar epithelial cell morphology PMID: 15968000 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0004244 abnormal spontaneous abortion rate PMID: 15138255 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0006055 abnormal vascular endothelial cell morphology PMID: 15138255 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004742 abnormal vestibular system physiology PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0000034 abnormal vestibule morphology PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0006359 absent startle reflex PMID: 17287522 
S1pr2tm1Jch|S1pr3+|S1pr3tm1Jch S1pr3tm1Jch/S1pr3+,S1pr2tm1Jch/S1pr2tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0006359 absent startle reflex PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004518 absent vestibular hair cell stereocilia PMID: 17287522 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0002857 cochlear ganglion degeneration PMID: 17284444 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0002857 cochlear ganglion degeneration PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004398 cochlear inner hair cell degeneration PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004404 cochlear outer hair cell degeneration PMID: 17287522 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MP:0001935 decreased litter size PMID: 11443127 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0001935 decreased litter size PMID: 12006579 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ
MGI:1339365  MP:0009764 decreased sensitivity to induced morbidity/mortality PMID: 18305483 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ
MGI:1339365  MP:0008734 decreased susceptibility to endotoxin shock PMID: 18305483 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0002757 decreased vertical activity PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004465 degeneration of organ of Corti supporting cells PMID: 17287522 
S1pr1tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MP:0006207 embryonic lethality during organogenesis PMID: 15138255 
S1pr1tm1Rlp|S1pr2tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MGI:99569  MP:0006207 embryonic lethality during organogenesis PMID: 15138255 
S1pr3tm1Jch S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ
MGI:1339365  MP:0008466 enlarged mesenteric lymph nodes PMID: 18305483 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0005191 head tilt PMID: 17284444 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0005191 head tilt PMID: 17287522 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0001914 hemorrhage PMID: 15138255 
S1pr1tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MP:0001914 hemorrhage PMID: 15138255 
S1pr1tm1Rlp|S1pr2tm1Rlp|S1pr3tm1Rlp S1pr1tm1Rlp/S1pr1tm1Rlp,S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1096355  MGI:1339365  MGI:99569  MP:0001914 hemorrhage PMID: 15138255 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0001523 impaired righting response PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0001522 impaired swimming PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0001513 limb grasping PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0000043 organ of Corti degeneration PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0002081 perinatal lethality PMID: 12006579 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0002080 prenatal lethality PMID: 15138255  17284444 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0001921 reduced fertility PMID: 15138255 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004331 saccular macula degeneration PMID: 17287522 
S1pr2tm1Rlp|S1pr3tm1Rlp S1pr3tm1Rlp/S1pr3tm1Rlp,S1pr2tm1Rlp/S1pr2tm1Rlp
involves: 129S6/SvEvTac * C57BL/6
MGI:1339365  MGI:99569  MP:0001786 skin edema PMID: 15138255 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004334 utricular macular degeneration PMID: 17287522 
S1pr2tm1Jch|S1pr3tm1Jch S1pr2tm1Jch/S1pr2tm1Jch,S1pr3tm1Jch/S1pr3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6N
MGI:1339365  MGI:99569  MP:0004324 vestibular hair cell degeneration PMID: 17287522 
General Comments
Hill et al. (2018) report on studies that show the involvement of S1PR3 in the generation of pain and itch [17]. They conclude that S1PR3 acts through TRPV1 channels (αq/PLC/PIP2 cleavage dependent) in heat nociceptors to mediate pain sensation, and through TRPA1 channels (βγ subunit dependent) in pruriceptors to mediate itch, and that identifying the role played by S1PR3 in these sensations paves the way for the development of S1PR3 modulators for managing pain and itch.

References

Show »

1. An S, Zheng Y, Bleu T. (2000) Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. J. Biol. Chem., 275 (1): 288-96. [PMID:10617617]

2. Ancellin N, Hla T. (1999) Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. J. Biol. Chem., 274 (27): 18997-9002. [PMID:10383399]

3. Awojoodu AO, Ogle ME, Sefcik LS, Bowers DT, Martin K, Brayman KL, Lynch KR, Peirce-Cottler SM, Botchwey E. (2013) Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis. Proc. Natl. Acad. Sci. U.S.A., 110 (34): 13785-90. [PMID:23918395]

4. Bajwa A, Huang L, Ye H, Dondeti K, Song S, Rosin DL, Lynch KR, Lobo PI, Li L, Okusa MD. (2012) Dendritic cell sphingosine 1-phosphate receptor-3 regulates Th1-Th2 polarity in kidney ischemia-reperfusion injury. J. Immunol., 189 (5): 2584-96. [PMID:22855711]

5. Banno Y, Takuwa Y, Akao Y, Okamoto H, Osawa Y, Naganawa T, Nakashima S, Suh PG, Nozawa Y. (2001) Involvement of phospholipase D in sphingosine 1-phosphate-induced activation of phosphatidylinositol 3-kinase and Akt in Chinese hamster ovary cells overexpressing EDG3. J. Biol. Chem., 276 (38): 35622-8. [PMID:11468290]

6. Baudhuin LM, Jiang Y, Zaslavsky A, Ishii I, Chun J, Xu Y. (2004) S1P3-mediated Akt activation and cross-talk with platelet-derived growth factor receptor (PDGFR). FASEB J., 18 (2): 341-3. [PMID:14657000]

7. Bolli MH, Abele S, Binkert C, Bravo R, Buchmann S, Bur D, Gatfield J, Hess P, Kohl C, Mangold C et al.. (2010) 2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. J. Med. Chem., 53 (10): 4198-211. [PMID:20446681]

8. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P et al.. (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem., 277 (24): 21453-7. [PMID:11967257]

9. Cinamon G, Zachariah MA, Lam OM, Foss Jr FW, Cyster JG. (2008) Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat. Immunol., 9 (1): 54-62. [PMID:18037889]

10. Davis MD, Clemens JJ, Macdonald TL, Lynch KR. (2005) Sphingosine 1-phosphate analogs as receptor antagonists. J. Biol. Chem., 280 (11): 9833-41. [PMID:15590668]

11. Demont EH, Bailey JM, Bit RA, Brown JA, Campbell CA, Deeks N, Dowell SJ, Eldred C, Gaskin P, Gray JR et al.. (2016) Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses. J. Med. Chem., 59 (3): 1003-20. [PMID:26751273]

12. Deng Q, Clemas JA, Chrebet G, Fischer P, Hale JJ, Li Z, Mills SG, Bergstrom J, Mandala S, Mosley R et al.. (2007) Identification of Leu276 of the S1P1 receptor and Phe263 of the S1P3 receptor in interaction with receptor specific agonists by molecular modeling, site-directed mutagenesis, and affinity studies. Mol. Pharmacol., 71 (3): 724-35. [PMID:17170199]

13. Donovan EE, Pelanda R, Torres RM. (2010) S1P3 confers differential S1P-induced migration by autoreactive and non-autoreactive immature B cells and is required for normal B-cell development. Eur. J. Immunol., 40 (3): 688-98. [PMID:20039302]

14. Forrest M, Sun SY, Hajdu R, Bergstrom J, Card D, Doherty G, Hale J, Keohane C, Meyers C, Milligan J et al.. (2004) Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J. Pharmacol. Exp. Ther., 309 (2): 758-68. [PMID:14747617]

15. Foss FW, Snyder AH, Davis MD, Rouse M, Okusa MD, Lynch KR, Macdonald TL. (2007) Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg. Med. Chem., 15 (2): 663-77. [PMID:17113298]

16. Herr DR, Lee CW, Wang W, Ware A, Rivera R, Chun J. (2013) Sphingosine 1-phosphate receptors are essential mediators of eyelid closure during embryonic development. J. Biol. Chem., 288 (41): 29882-9. [PMID:24003216]

17. Hill RZ, Motita T, Brem RB, Bautista DM. (2018) S1PR3 mediates itch and pain via distinct TRP channel-dependent pathways. Journal of Neuroscience, Early release. DOI: 10.1523/JNEUROSCI.1266-18.2018

18. Idzko M, Panther E, Corinti S, Morelli A, Ferrari D, Herouy Y, Dichmann S, Mockenhaupt M, Gebicke-Haerter P, Di Virgilio F et al.. (2002) Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. FASEB J., 16 (6): 625-7. [PMID:11919175]

19. Im DS, Clemens J, Macdonald TL, Lynch KR. (2001) Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors. Biochemistry, 40 (46): 14053-60. [PMID:11705398]

20. Ishii I, Friedman B, Ye X, Kawamura S, McGiffert C, Contos JJ, Kingsbury MA, Zhang G, Brown JH, Chun J. (2001) Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3. J. Biol. Chem., 276 (36): 33697-704. [PMID:11443127]

21. Kennedy PC, Zhu R, Huang T, Tomsig JL, Mathews TP, David M, Peyruchaud O, Macdonald TL, Lynch KR. (2011) Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J. Pharmacol. Exp. Ther., 338 (3): 879-89. [PMID:21632869]

22. Kon J, Sato K, Watanabe T, Tomura H, Kuwabara A, Kimura T, Tamama K, Ishizuka T, Murata N, Kanda T et al.. (1999) Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor subtypes to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells. J. Biol. Chem., 274 (34): 23940-7. [PMID:10446161]

23. Kono M, Mi Y, Liu Y, Sasaki T, Allende ML, Wu YP, Yamashita T, Proia RL. (2004) The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J. Biol. Chem., 279 (28): 29367-73. [PMID:15138255]

24. Li Z, Chen W, Hale JJ, Lynch CL, Mills SG, Hajdu R, Keohane CA, Rosenbach MJ, Milligan JA, Shei GJ et al.. (2005) Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3. J. Med. Chem., 48 (20): 6169-73. [PMID:16190743]

25. Means CK, Xiao CY, Li Z, Zhang T, Omens JH, Ishii I, Chun J, Brown JH. (2007) Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol., 292 (6): H2944-51. [PMID:17293497]

26. Nofer JR, van der Giet M, Tölle M, Wolinska I, von Wnuck Lipinski K, Baba HA, Tietge UJ, Gödecke A, Ishii I, Kleuser B et al.. (2004) HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J. Clin. Invest., 113 (4): 569-81. [PMID:14966566]

27. Ogle ME, Olingy CE, Awojoodu AO, Das A, Ortiz RA, Cheung HY, Botchwey EA. (2017) Sphingosine-1-Phosphate Receptor-3 Supports Hematopoietic Stem and Progenitor Cell Residence Within the Bone Marrow Niche. Stem Cells, 35 (4): 1040-1052. [PMID:28026131]

28. Okamoto H, Takuwa N, Gonda K, Okazaki H, Chang K, Yatomi Y, Shigematsu H, Takuwa Y. (1998) EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition. J. Biol. Chem., 273 (42): 27104-10. [PMID:9765227]

29. Okamoto H, Takuwa N, Yatomi Y, Gonda K, Shigematsu H, Takuwa Y. (1999) EDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16. Biochem. Biophys. Res. Commun., 260 (1): 203-8. [PMID:10381367]

30. Pan S, Gray NS, Gao W, Mi Y, Fan Y, Wang X, Tuntland T, Che J, Lefebvre S, Chen Y et al.. (2013) Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator. ACS Med Chem Lett, 4 (3): 333-7. [PMID:24900670]

31. Pan S, Mi Y, Pally C, Beerli C, Chen A, Guerini D, Hinterding K, Nuesslein-Hildesheim B, Tuntland T, Lefebvre S et al.. (2006) A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem. Biol., 13 (11): 1227-34. [PMID:17114004]

32. Riganti L, Antonucci F, Gabrielli M, Prada I, Giussani P, Viani P, Valtorta F, Menna E, Matteoli M, Verderio C. (2016) Sphingosine-1-Phosphate (S1P) Impacts Presynaptic Functions by Regulating Synapsin I Localization in the Presynaptic Compartment. J. Neurosci., 36 (16): 4624-34. [PMID:27098703]

33. Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N et al.. (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J. Biol. Chem., 279 (14): 13839-48. [PMID:14732717]

34. Sanna MG, Vincent KP, Repetto E, Nguyen N, Brown SJ, Abgaryan L, Riley SW, Leaf NB, Cahalan SM, Kiosses WB et al.. (2016) Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction. Mol. Pharmacol., 89 (1): 176-86. [PMID:26494861]

35. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H et al.. (2016) Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity. Br. J. Pharmacol., 173 (11): 1778-92. [PMID:26990079]

36. Theilmeier G, Schmidt C, Herrmann J, Keul P, Schäfers M, Herrgott I, Mersmann J, Larmann J, Hermann S, Stypmann J et al.. (2006) High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation, 114 (13): 1403-9. [PMID:16982942]

37. Van Brocklyn JR, Tu Z, Edsall LC, Schmidt RR, Spiegel S. (1999) Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G protein-coupled receptor H218. J. Biol. Chem., 274 (8): 4626-32. [PMID:9988698]

38. Weth-Malsch D, Langeslag M, Beroukas D, Zangrandi L, Kastenberger I, Quarta S, Malsch P, Kalpachidou T, Schwarzer C, Proia RL et al.. (2016) Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron Excitability In vitro and Spatial Working Memory In vivo. Front Cell Neurosci, 10: 258. [PMID:27872583]

39. Windh RT, Lee MJ, Hla T, An S, Barr AJ, Manning DR. (1999) Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the G(i), G(q), and G(12) families of heterotrimeric G proteins. J. Biol. Chem., 274 (39): 27351-8. [PMID:10488065]

40. Yamamoto R, Okada Y, Hirose J, Koshika T, Kawato Y, Maeda M, Saito R, Hattori K, Harada H, Nagasaka Y et al.. (2014) ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS ONE, 9 (10): e110819. [PMID:25347187]

41. Yang AH, Ishii I, Chun J. (2002) In vivo roles of lysophospholipid receptors revealed by gene targeting studies in mice. Biochim. Biophys. Acta, 1582 (1-3): 197-203. [PMID:12069829]

42. Zhang G, Contos JJ, Weiner JA, Fukushima N, Chun J. (1999) Comparative analysis of three murine G-protein coupled receptors activated by sphingosine-1-phosphate. Gene, 227 (1): 89-99. [PMID:9931453]

Contributors

Show »

How to cite this page

Yasuyuki Kihara, Victoria Blaho, Hirotaka Mizuno, Jerold Chun.
Lysophospholipid (S1P) receptors: S1P3 receptor. Last modified on 07/08/2018. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=277.