Nomenclature: P2Y6 receptor

Family: P2Y receptors

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

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 328 11q13.5 P2RY6 pyrimidinergic receptor P2Y, G-protein coupled, 6 7,23
Mouse 7 328 7 E1 P2ry6 pyrimidinergic receptor P2Y, G-protein coupled, 6 22
Rat 7 328 1q32 P2ry6 pyrimidinergic receptor P2Y, G-protein coupled, 6 1
Previous and Unofficial Names
uridine nucleotide receptor
pyrimidinoceptor
P2Y6
P2Y ATP receptor 6
P2Y purinoceptor 6
pyrimidinergic receptor P2Y, G-protein coupled, 6
2010204J23Rik
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
UDP
UTP
Rank order of potency (Human)
UDP>>UTP>ATP
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 18a [PMID:22901672] Hs Agonist 8.1 pEC50 13
pEC50 8.1 (EC50 8x10-9 M) [13]
MRS2957 Hs Agonist 7.9 pEC50 29
pEC50 7.9 (EC50 1.2x10-8 M) [29]
5-iodoUDP Hs Full agonist 7.82 pEC50 3
pEC50 7.82 (EC50 1.5x10-8 M) [3]
UDP-β-S Hs Full agonist 7.55 pEC50 4
pEC50 7.55 [4]
3-phenacyl-UDP Hs Full agonist 7.2 pEC50 10
pEC50 7.2 [10]
INS48823 Hs Full agonist 6.9 pEC50 4
pEC50 6.9 [4]
Up3U Hs Full agonist 6.7 pEC50 4
pEC50 6.7 [4]
UDP Hs Full agonist 6.5 pEC50 7
pEC50 6.5 [7]
MRS2782 Hs Full agonist 6.18 pEC50 18
pEC50 6.18 [18]
5BrUTP Hs Partial agonist 6.1 pEC50 7
pEC50 6.1 [7]
UTP Hs Partial agonist 5.2 pEC50 7
pEC50 5.2 [7]
ADP Hs Partial agonist 4.5 pEC50 7
pEC50 4.5 [7]
2MeSATP Hs Partial agonist 4.0 pEC50 7
pEC50 4.0 [7]
Agonist Comments
INS48823 has also been shown to act as an agonist at the rabbit P2Y6 receptor [20].

Reference [7] EC50 values are found using IP3 functional assays.

The combination of molecular dynamics (MD) in a hydrated phospholipid (DOPC) bilayer, Monte Carlo search, and synthesis of locked nucleotide analogues, showed that the Southern conformation of the ribose is preferred for ligand recognition by the P2Y6 receptor [8]

Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
MRS2578 Hs Antagonist 7.4 pIC50 26
pIC50 7.4 [26]
MRS2567 Rn Antagonist 7.0 pIC50 26
pIC50 7.0 [26]
MRS2578 Rn Antagonist 7.0 pIC50 26
pIC50 7.0 [26]
MRS2567 Hs Antagonist 6.9 pIC50 26
pIC50 6.9 [26]
reactive blue-2 Hs Antagonist 4.5 pIC50 4
pIC50 4.5 (IC50 3.1x10-5 M) [4]
View species-specific antagonist tables
Antagonist Comments
MRS2578 is an insurmontable, non-competitive antagonist [26]. In 1321N1 cells transfected with the human P2Y6receptor, cysLT1 antagonists were demonstrated to inhibit UDP-mediated PLC activation (pIC50 <6)[25]
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References: 
Secondary Transduction Mechanisms
Transducer Effector/Response
G12/G13 family Other - See Comments
Comments:  Activation of Rho and c-Jun kinase. Coupling of P2Y6 to G12/G13 was demonstrated in mouse cardiomyocytes, leading to the increased expression of fibrogenic genes (TGF-beta, connective tissue growth factor, and periostin) and Ang-converting enzyme (ACE) [32].
References:  32,45
Tissue Distribution
Cardiomyocytes
Species:  Human
Technique:  real time PCR
References:  44
Bone.
Species:  Human
Technique:  RT-PCR.
References:  23
Bronchial epithelium
Species:  Human
Technique:  real time PCR
References:  45
Brain: cingulate gyrus > amygdala > nucleus accumbens, putamen > globus pallidus > medulla oblongata, parahippocampal gyrus, striatum, substantia nigra, hypothalamus, hippocampus, locus coeruleus > caudate nucleus, cerebellum, superior frontal gyrus, spinal cord > thalamus >> medial frontal gyrus.
Species:  Human
Technique:  RT-PCR.
References:  30
Spleen > placenta > lung, thymus, small intestine, blood leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  7
Retinal Müller glial cells
Species:  Human
Technique:  Immunohistochemistry, single cell RT-PCR
References:  11
Microvascular endothelial cells
Species:  Human
Technique:  RT-PCR and Western blotting, immunofluorescence
References:  36
Bone marrow stromal cells
Species:  Human
Technique:  RT-PCR and Western blotting
References:  33,47
Spleen > placenta >> kidney > intestine, adipose, bone, lung > heart, brain, skeletal muscle, stomach > pituitary, foetal liver, lymphocytes, cartilage > liver, macrophages, pancreas, prostate, bone marrow.
Species:  Human
Technique:  RT-PCR.
References:  30
Placenta, skeletal muscle > brain, heart, liver, pancreas.
Species:  Human
Technique:  Northern blotting.
References:  23
Skeletal muscle
Species:  Mouse
Technique:  RT-PCR and Western blotting, immunofluorescence
References:  6
Isolated pancreatic islets and purified beta-cells
Species:  Mouse
Technique:  real time PCR
References:  35
Microvascular endothelial cells
Species:  Mouse
Technique:  RT-PCR and Western blotting, immunofluorescence
References:  36
Gallbladder.
Species:  Mouse
Technique:  in situ hybridisation.
References:  22
Atherosclerotic plaques in aorta
Species:  Mouse
Technique:  RT-PCR
References:  15
Endolymphatic sac epithelia
Species:  Rat
Technique:  RT-PCR
References:  31
Kidney: proximal tubule, thick ascending limb of Henle's loop > thin descending limb, cortical and outer medullary conducting ducts.
Species:  Rat
Technique:  RT-PCR.
References:  1
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]

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Functional Assays
Measurement of Ca2+ levels in response to the P2Y6 agonist UDP in mouse peritoneal macrophage cells.
Species:  Mouse
Tissue:  Peritoneal macrophages.
Response measured:  Increase in [Ca2+]i.
References:  9
Measurement of IP levels and Ca2+ concentration in 1321N1 cells transfected with the mouse P2Y6 receptor.
Species:  Mouse
Tissue:  1321N1 cells.
Response measured:  IP accumulation and increase in [Ca2+].
References:  7,22
Bioelectrical measurement of short-circuit current (ISC) in response to P2Y6 agonist stimulation in gallbladder epithelial cells.
Species:  Mouse
Tissue:  Gallbladder epithelia
Response measured:  Increase in ISC.
References:  22
Measurement of IP3 and Ca2+ levels in rat proximal tubule.
Species:  Rat
Tissue:  Proximal tubule.
Response measured:  Increase in IP3 and Ca2+ levels.
References:  1
Modulation of intracellular calcium concentrations
Species:  Mouse
Tissue:  Satellite glial cells from trigeminal ganglia
Response measured:  Increases in the intracellular calcium concentrations
References:  5
Physiological Functions
Cl- secretion.
Species:  Mouse
Tissue:  Trachea.
References:  39
Proliferation of tumour cells.
Species:  Human
Tissue:  Lung epithelial tumour cells.
References:  38
Contraction of smooth muscle.
Species:  Human
Tissue:  Cerebral arteries.
References:  24
NaCl secretion mediated via an increase in [Ca2+] and cAMP.
Species:  Rat
Tissue:  Basolateral membrane of colonic epithelium.
References:  21
DNA synthesis.
Species:  Rat
Tissue:  Aorta smooth muscle cells.
References:  16
Interleukin-8 release.
Species:  Human
Tissue:  THP-1 monocyte cells.
References:  43
Modulation of microglial phagocytosis
Species:  Rat
Tissue:  Brain
References:  19
Modulation of insulin and glucagone secretion
Species:  Mouse
Tissue:  Isolated pancreatic islets and purified β-cells
References:  35
Cross-talk with complement component 5a (C5a) in modulating calcium release from intracellular stores, through PLCβ3
Species:  Mouse
Tissue:  Macrophages
References:  37
Protection from apoptosis both in vitro and in vivo
Species:  Mouse
Tissue:  Skeletal muscle
References:  27
Positive inotropic effect
Species:  Mouse
Tissue:  Cardiomyocytes
References:  44
Stimulation of Ca2+-dependent chloride secretion. The cAMP/PKA pathway regulates apical but not basolateral P2Y6 receptor-coupled ion transport
Species:  Human
Tissue:  Bronchial epithelium
References:  45
Increased expression and release of CCL2
Species:  Mouse
Tissue:  Macrophages
References:  46
Increased expression of CCL2 and CCL3
Species:  Rat
Tissue:  Microglia
References:  17
Increased expression and release of CXCL8
Species:  Mouse
Tissue:  Intestinal epithelial cells
References:  14
Expression of fibrogenic genes and cardiac fibrosis
Species:  Mouse
Tissue:  Cardiomyocytes
References:  32
Inhibition of IFN-α production and induction of immune tolerance
Species:  Human
Tissue:  Plasmacytoid dendritic cells
References:  28,40
Release of IL-1, IL-6 and IL-8 in response to urate crystals
Species:  Human
Tissue:  Keratinocytes
References:  41
Physiological Consequences of Altering Gene Expression
P2Y6 knock-out mice exhibit a reduced macrophage response to UDP and LPS, and the abolition of endothelium-dependent aorta relaxation and of smooth muscle-dependent aorta contraction by UDP.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  2
P2Y6 knock-out mice exhibit attenuated inflammatory responses during LPS-induced vascular inflammation
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  36
P2Y6 knock-out mice exhibit a reduction of cardinal features of asthma, such as bronchoalveolar lavage eosinophilia, airway remodeling, Th2 cytokine production, and bronchial hyperresponsiveness in the ovalbumin-alum model.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  42
P2Y6 knock-out mice exhibit an enhanced airway pathology and CD4+ T cells proliferation and cytokine production in the dust mite model of allergic pulmonary inflammation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  12
P2Y6 knock-out mice exhibit an increased bone mineral content, cortical bone volume, and cortical thickness in the long bones and spine, as a result of a defective bone resorption by osteoclasts.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  34
General Comments
In mouse bone marrow-derived mast cells (mBMMCs) and in the human MC line LAD2, P2Y6 receptors cooperate with CysLT1R to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk [18].
Available Assays
DiscoveRx PathHunter® CHO-K1 P2RY6 β-Arrestin Cell Line (Cat no. 93-0500C2)
PathHunter® eXpress P2RY6 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0500E2CP19M)
more info

REFERENCES

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25. Mamedova L, Capra V, Accomazzo MR, Gao ZG, Ferrario S, Fumagalli M, Abbracchio MP, Rovati GE, Jacobson KA. (2005) CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors. Biochem Pharmacol71: 115-125. [PMID:16280122]

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To cite this database page, please use the following:

Maria-Pia Abbracchio, Jean-Marie Boeynaems, José L. Boyer, Geoffrey Burnstock, Stefania Ceruti, Marta Fumagalli, Christian Gachet, Rebecca Hills, Robert G. Humphries, Kenneth A. Jacobson, Charles Kennedy, Brian F. King, Davide Lecca, Maria Teresa Miras-Portugal, Gary A. Weisman.
P2Y receptors: P2Y6 receptor. Last modified on 12/08/2013. Accessed on 21/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=326.

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