Nomenclature: P2Y2 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 7 377 11q13.5-q14.1 P2RY2 purinergic receptor P2Y, G-protein coupled, 2 56
Mouse 7 373 7 F1 P2ry2 purinergic receptor P2Y, G-protein coupled 2 50
Rat 7 374 1q32 P2ry2 purinergic receptor P2Y, G-protein coupled, 2 27,68
Previous and Unofficial Names
P2U
P2U
P2Y2
ATP receptor
P2U purinoceptor 1
P2U1
P2Y ATP receptor 2
P2Y purinoceptor 2
purinergic receptor P2Y, G-protein coupled 2
purinergic receptor P2Y, G-protein coupled, 2
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
ATP
UTP
Rank order of potency (Human)
UTP=ATP
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
UTP Hs Full agonist 8.1 pEC50 38,46
pEC50 8.1 [38,46]
MRS2698 Hs Full agonist 8.1 pEC50 34
pEC50 8.1 [34]
4-thio-UTP Hs Full agonist 7.5 pEC50 9
pEC50 7.5 [9]
2-thioUTP Hs Agonist 7.3 pEC50 23
pEC50 7.3 (EC50 5x10-8 M) [23]
ATP Hs Full agonist 7.1 pEC50 38,46
pEC50 7.1 [38,46]
diquafosol Hs Full agonist 7.0 pEC50 58
pEC50 7.0 [58]
PSB1114 Hs Full agonist 6.9 pEC50 24
pEC50 6.9 (EC50 1.34x10-7 M) EC50 value determined using an IP3 functional assay [24]
denufosol Hs Full agonist 6.7 pEC50 77
pEC50 6.7 [77]
Ap4A Hs Full agonist 6.1 pEC50 12,57
pEC50 6.1 [12,57]
UTPγS Hs Full agonist 5.8 pEC50 46
pEC50 5.8 [46]
MRS2768 Hs Full agonist 5.7 pEC50 40
pEC50 5.7 (EC50 1.89x10-6 M) EC50 value determined using an IP3 functional assay [40]
5BrUTP Hs Full agonist 5.7 pEC50 46
pEC50 5.7 [46]
Agonist Comments
PSB1114 is a potent, selective P2Y2 agonist with >60-fold selectivity for versus P2Y4 and P2Y6 receptors [24].

Reference [46] EC50 values are found using IP3 functional assays.
References [58,77] EC50 values are found using Ca2+ functional assays.

A library of nucleotide triphosphates incorporating a C-linked unnatural base (i.e., benzothiazole, benzoxazole and benzimidazole) was synthesized, a number of which offer potency comparable to that of the N-linked series, and significantly more stability than UTP [18].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
AR-C126313 Hs Antagonist 6.0 pEC50 34
pEC50 6.0 [34]
AR-C118925XX Hs Antagonist ~6.0 pIC50 36
pIC50 ~6.0 (IC50 ~1x10-6 M) [36]
reactive blue-2 Hs Antagonist 6.0 pIC50 35
pIC50 6.0 [35]
suramin Hs Antagonist 4.3 pIC50 65
pIC50 4.3 [65]
Antagonist Comments
The rat P2Y2R is virtually insensitive to Reactive Blue 2 (pIC50 > 2) [9].

Although non-selective, suramin can be useful to discriminate between the P2Y2 and the P2Y4 receptor subtypes, the latter being insensitive to its antagonism [9].

A small library of 1-amino-4-phenylamino-2-sulfoanthraquinone derivatives related to Reactive Blue 2 has been synthesized, and some of them proved to be potential P2Y2R antagonists with low micromolar IC50 values [73].
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  In bronchial and intestinal epithelia, activation of P2Y2 receptor subtype leads to stimulation of chloride secretion through Gq/G11, and phospholipase C activation followed by inhibition of Na+ transport [21,31,76]
References:  72,76
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G12/G13 family
Other - See Comments
Comments:  In hP2Y2R-transfected 1321N1 cells, P2Y2 receptor was found to couple through integrins to Gi/Go, leading to Rac activation, vitronectin up-regulation and increasing cell migration [6], and to G12, leading to Rho activation, cofilin and myosin light chain-2 phosphorylation, stress fiber formation and chemotaxis towards UTP [48]. Coupling of P2Y2 receptor to hematopoietic cell specific Gα16, belonging to the Gq family, was found in human erythroleukemia cells [43]. In the presence of nerve growth factor (NGF), the interaction between the P2Y2 receptor and tyrosine kinase A (TrkA) through Src was detected, followed by activation of ERK1/2 [3-4].
References:  6,48
Tissue Distribution
Bronchial epithelium
Species:  Human
Technique:  realtime PCR
References:  75
Middle ear epithelial cells
Species:  Human
Technique:  Immunohistochemistry
References:  14
Brain: putamen, striatum > caudate nucleus, hypothalamus, medulla oblongata, substantia nigra, thalamus, spinal cord, locus coeruleus > amygdala, globus pallidus, hippocampus, nucleus accumbens, parahippocampal gyrus, superior frontal gyrus > cerebellum, cingulate gyrus > medial frontal gyrus.
Species:  Human
Technique:  RT-PCR.
References:  53
P2Y2 receptor expression is upregulated in the submandibular glands of the NOD.B10 mouse model of Sjogren's Syndrome
Species:  Mouse
Technique:  RT-PCR
References:  67
Dorsal root ganglia neurons
Species:  Rat
Technique:  In situ hydridisation
References:  41
Aortic smooth muscle cells.
Species:  Rat
Technique:  Northern blotting.
References:  68
P2Y2 receptor upregulation during submandibular gland duct ligation is reversible following duct deligation
Species:  Rat
Technique:  RT-PCR
References:  1
Liver > testis > esophagus > lung, trachea > heart, skeletal muscle > stomach, kidney.
Species:  Rat
Technique:  Northern blotting.
References:  27
Mucus-secreting cells of nasal epithelium
Species:  Rat
Technique:  Immunohistochemistry
References:  29
Endolymphatic sac epithelia
Species:  Rat
Technique:  RT-PCR
References:  54
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
Modulation of amiloride-sensitive Na+ transport by PIP2 hydrolysis
Species:  Rat
Tissue:  Xenopus oocytes
Response measured:  Inhibition of Na+ currents
References:  45
Measurement of Ca2+ levels and spontaneous transient outward current (STOCs) in vascular smooth muscle (A7r5) cells transfected with a chimera of the P2Y2R and green fluorescent protein (P2Y2R-GFP).
Species:  Human
Tissue:  A7r5 cells.
Response measured:  Increase in [Ca2+]i levels and subsequent generation of STOCs.
References:  47
The voltage-clamp technique was used to measure the ionic membrane currents in cultured mouse cumulus cell-enclosed oocytes (CEOs) in response to P2Y2 receptor agonists.
Species:  Mouse
Tissue:  Cultured cumulus cell-enclosed oocytes (CEOs).
Response measured:  Opening of Ca2+-dependent Cl- channels and Ca2+-independent Na+ channels. Subsequent depolarisation and opening of voltage-sensitive K+ channels.
References:  2
Assay for the processing of amyloid precursor protein (APP) by P2Y2 receptors transfected into 1321N1 cells.
Species:  Human
Tissue:  1321N1 astrocytoma cells.
Response measured:  Release of sAPPα, dependent on extracellular Ca2+ levels.
References:  11
Following mechanical stimulation of an individual 1321N1 cell, measurement of Ca2+ propagation in 1321N1 cells transfected with the P2Y2R
Species:  Rat
Tissue:  1321N1 cells.
Response measured:  Ca2+ wave only spread to cells expressing the P2Y2 receptor. P2Y2 is not required for the initiation of the wave.
References:  28
Measurement of Ca2+ levels in response to the P2Y2R agonist UTP in mouse peritoneal macrophage cells.
Species:  Mouse
Tissue:  Peritoneal macrophages.
Response measured:  Increase in [Ca2+]i.
References:  16
Measurement of [Ca2+]i in human glioma C6 cells endogenously expressing P2Y1 and P2Y2 receptors.
Species:  Human
Tissue:  Glioma C6 cells.
Response measured:  Increase in [Ca2+]i.
References:  63
Measurement of IP3 levels in response to selective P2Y2R agonists in HEK 293 cells endogenously expressing the P2Y1 and P2Y2 receptors.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  IP3 accumulation.
References:  66
Measurement of [Ca2+]i in K-562 cells (human leukemia cell line) transfected with the human P2Y2 receptor.
Species:  Human
Tissue:  K-562.
Response measured:  Increase in [Ca2+]i.
References:  26
Physiological Functions
Activation of luminal K+ secretion
Species:  Mouse
Tissue:  Colon
References:  52
The P2Y2 receptor mediates the chloride secretory response in the jejunum along with the P2Y4 receptor.
Species:  Mouse
Tissue:  Jejunum.
References:  31
Increase in coronary blood flow by vasodilation.
Species:  Rat
Tissue:  Isolated heart.
References:  27
Migration of vascular smooth muscle cells
Species:  Mouse
Tissue:  Vascular smooth muscle cells
References:  78
Orientation of neutrophil chemotaxis
Species:  Human
Tissue:  Neutrophils
References:  13
Inhibition of apoptosis
Species:  Rat
Tissue:  PC12 cells, dorsal root ganglia
References:  5
Positive inotropism
Species:  Human
Tissue:  Heart
References:  74
Presynaptic inhibition of glutamate release
Species:  Rat
Tissue:  Hippocampus
References:  62
Stimulation of ciliary beat and Cl- secretion; modulation of mucin release
Species:  Human
Tissue:  Airway epithelia
References:  19,21
Blockade of bone mineralization
Species:  Rat
Tissue:  Primary osteoblasts
References:  55
A study using P2Y2R knockout mice show that P2Y2 receptors are involved in the mediation of ion transport in the trachea and the gallbladder.
Species:  Mouse
Tissue:  Trachea and gallbladder.
References:  17
Control of cellular proliferation, spreading and migration.
Species:  Human
Tissue:  Keratinocytes of the epidermis
References:  22,72
Vasopressin-independent control of the osmotic water permeability of the inner medullary collecting duct of the kidney
Species:  Rat
Tissue:  Inner madullary cells
References:  39,59,70-71,80
Increased P2Y2 receptor expression through NF-κB activation stimulates cyclooxygenase-2 expression and prostaglandin-E2 release
Species:  Human
Tissue:  Colon adenocarcinoma cell line
References:  20
P2Y2 receptor activation induces electrogenic bicarbonate secretion across CFTR knockout epithelium
Species:  Mouse
Tissue:  Gallbladder epithelium
References:  15
P2Y2 receptor activation stimulates ERK1/2 activation in human monocytic cells
Species:  Human
Tissue:  U937 monocytic cells
References:  64
P2Y2 receptor activation stimulates the activity of Src, Pyk2, and EGFR via Src homology 3 binding sites in the C-terminal tail
Species:  Human
Tissue:  1321N1 astrocytoma cells
References:  49
P2Y2 receptor stimulates the upregulation of vascular cell adhesion molecule 1 in endothelial cells through interaction with VEGFR-2
Species:  Human
Tissue:  Human coronary artery endothelial cells
References:  69
Enhanced α-secretase-dependent APP processing following interleukin-1β-mediated P2Y2 receptor upregulation
Species:  Mouse
Tissue:  Primary cortical neurons
References:  42
P2Y2 receptors mediate metalloprotease-dependent phosphorylation of epidermal growth factor receptor and ErbB3
Species:  Human
Tissue:  Human salivary gland cell line
References:  60
P2Y2 receptor activation increases microglial cell migration and uptake of amyloid β1-42
Species:  Mouse
Tissue:  Primary microglia
References:  37
P2Y2 receptor activation promotes repair of alveolar epithelial cells following micropunture injury or stress deformation
Species:  Rat
Tissue:  Primary type 1 alveolar epithelial cells
References:  7
Physiological Consequences of Altering Gene Expression
P2Y2 receptor knockout mice exhibit abolished Ca2+ mobilisation in response to UTP.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  33
P2Y2 receptor knockout studies show that the P2Y2 receptor mediates most of the Cl- secretion in the trachea and around half in the gallbladder.
Species:  Mouse
Tissue:  Trachea and gallbladder
Technique:  Gene targeting in embryonic stem cells.
References:  17
P2Y2R-deficient mice showed salt-resistant arterial hypertension and facillitated Na+ and water renal reabsorption
Species:  Mouse
Tissue:  Kidney and arteries
Technique:  Gene targeting in embryonic stem cells
References:  61
P2Y2R-deficient mice showed impaired ATP- and adenosine 5'[γ-thio] triphosphate (ATPγS)-evoked relaxation of thoracic aorta segments
Species:  Mouse
Tissue:  Thoracic aorta
Technique:  Gene targeting in embryonic stem cells
References:  32
P2Y1R/P2Y2R double knock out mice showed an increased susceptibility to Pseudomonas aeruginosa infection (100% of death within 30 hours vs 15% in wild type mice)
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  30
Luminal colon UTP-stimulated K+ secretion was found completely absent in P2Y2R/P2Y4R double KO mice
Species:  Mouse
Tissue:  Colon
Technique:  Gene targeting in embryonic stem cells
References:  52
P2Y2R deficient mice showed profound deficits in UTP-evoked calcium transients in dorsal root ganglia and a potentiation of capsaicin responses. P2Y2R deficient mice were also deficient in the detection of painful heat.
Species:  Mouse
Tissue:  Dorsal root ganglion
Technique:  Gene targeting in embryonic stem cells
References:  51
P2Y2 receptor knockout mice exhibit a decreased chloride secretory response in the jejunum, but not the colon.
Species:  Mouse
Tissue:  Jejunum
Technique:  Gene targeting in embryonic stem cells.
References:  31
P2Y2 receptor knockout mice exhibit reduced K+ secretion in the luminal membrane of the distal colonic mucosa when compared to wild-type mice.
P2Y2R/P2Y4R double knockout mice have completely abolished K+ secretion in the distal colonic mucosa.
Species:  Mouse
Tissue:  Distal colonic mucosa
Technique:  Transgenesis.
References:  52
Significantly impaired recruitment of monocytes/macrophages and clearance of apoptotic thymocytes in P2Y2 receptor knockout mice
Species:  Mouse
Tissue:  Thymus
Technique:  Targeting in embryonic stem cells
References:  25
P2Y2 receptor knockout mice show significant resistance to the development of lithium-induced polyuria
Species:  Mouse
Tissue: 
Technique:  Targeting in embryonic stem cells
References:  79
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
P2ry2tm1Bhk P2ry2tm1Bhk/P2ry2tm1Bhk
involves: 129P2/OlaHsd
MGI:105107  MP:0003651 abnormal axon outgrowth PMID: 16365320 
P2ry2tm1Bhk P2ry2tm1Bhk/P2ry2tm1Bhk
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
MGI:105107  MP:0001765 abnormal ion homeostasis PMID: 10473605  10473606 
P2ry2tm1Bhk P2ry2tm1Bhk/P2ry2tm1Bhk
involves: 129P2/OlaHsd
MGI:105107  MP:0009937 abnormal neuron differentiation PMID: 16365320 
P2ry2tm1Bhk P2ry2tm1Bhk/P2ry2tm1Bhk
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
MGI:105107  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 10473605  10473606 
P2ry2tm1Bhk P2ry2tm1Bhk/P2ry2tm1Bhk
involves: 129P2/OlaHsd
MGI:105107  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 16365320 
Biologically Significant Variants
Type:  Naturally occurring mutations
Species:  Human
Description:  Three frequent nonsynonymous P2Y2 receptor polymorphisms have been identified, one of which was significantly more common in cystic fibrosis patients. This polymorphism is linked to increase in Ca2+ influx in transfected cells, and might therefore play a role in disease development or in P2Y2R agonist therapy to cystic fibrosis.
References:  10
General Comments
The three human transcript variants encode for the same 377 aa protein sequence [56]. P2Y2 receptors have been localized in mitochondria in rat astrocytes, C6 glioma cells and liver, suggesting their role in regulating mitochondrial calcium transport [8,44]. Denufosol tetrasodium is currently under evaluation as an inhaled treatment for cystic fibrosis (phase III clinical study), and diquafosol is in phase III clinical study for dry eye disease (http://clinicaltrials.gov/ct2/home).
Available Assays
DiscoveRx PathHunter® eXpress P2RY2 U2OS β-Arrestin GPCR Assay (Cat no. 93-0628E3CP5M)
PathHunter® U2OS P2RY2 β-Arrestin Cell Line (Cat no. 93-0628C3)
more info

REFERENCES

1. Ahn JS, Camden JM, Schrader AM, Redman RS, Turner JT. (2000) Reversible regulation of P2Y(2) nucleotide receptor expression in the duct-ligated rat submandibular gland. Am. J. Physiol., Cell Physiol.279 (2): C286-94. [PMID:10912994]

2. Arellano RO, Martinez-Torres A, Garay E. (2002) Ionic currents activated via purinergic receptors in the cumulus cell-enclosed mouse oocyte. Biol Reprod67: 837-846. [PMID:12193392]

3. Arthur DB, Akassoglou K, Insel PA. (2005) P2Y2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation. Proc Natl Acad Sci U S A.102: 19138-19143. [PMID:16365320]

4. Arthur DB, Akassoglou K, Insel PA. (2006) P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation. Biochem Biophys Res Commun347: 678-682. [PMID:16842754]

5. Arthur DB, Georgi S, Akassoglou K, Insel PA. (2006) Inhibition of apoptosis by P2Y2 receptor activation: novel pathways for neuronal survival. J Neurosci26: 3798-3804. [PMID:16597733]

6. Bagchi S, Liao Z, Gonzalez FA, Chorna NE, Seye CI, Weisman GA, Erb L. (2005) The P2Y2 nucleotide receptor interacts with alphav integrins to activate Go and induce cell migration. J Biol Chem280: 39050-39057. [PMID:16186116]

7. Belete HA, Hubmayr RD, Wang S, Singh RD. (2011) The role of purinergic signaling on deformation induced injury and repair responses of alveolar epithelial cells. PLoS ONE6 (11): e27469. [PMID:22087324]

8. Belous AE, Jones CM, Wakata A, Knox CD, Nicoud IB, Pierce J, Chari RS. (2006) Mitochondrial calcium transport is regulated by P2Y1- and P2Y2-like mitochondrial receptors. J Cell Biochem99: 1165-1174. [PMID:16795051]

9. Brunschweiger A, Müller CE. (2006) P2 receptors activated by uracil nucleotides--an update. Curr Med Chem13: 289-312. [PMID:16475938]

10. Büscher R, Hoerning A, Patel HH, Zhang S, Arthur DB, Grasemann H, Ratjen F, Insel PA. (2006) P2Y2 receptor polymorphisms and haplotypes in cystic fibrosis and their impact on Ca2+ influx. Pharmacogenet. Genomics16 (3): 199-205. [PMID:16495779]

11. Camden JM, Schrader AM, Camden RE, Gonzalez FA, Erb L, Seye CI, Weisman GA. (2005) P2Y2 nucleotide receptors enhance alpha-secretase-dependent amyloid precursor protein processing. J Biol Chem280: 18696-18702. [PMID:15778502]

12. Castro E, Pintor J, Miras-Portugal MT. (1992) Ca(2+)-stores mobilization by diadenosine tetraphosphate, Ap4A, through a putative P2Y purinoceptor in adrenal chromaffin cells. Br. J. Pharmacol.106 (4): 833-7. [PMID:1393282]

13. Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG. (2006) ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science314: 1792-1795. [PMID:17170310]

14. Choi JY, Shin JH, Kim JL, Jung SH, Son EJ, Song MH, Kim SH, Yoon JH. (2005) P2Y2 agonist induces mucin secretion via Ca2+- and inositol 1,4,5-triphosphate-dependent pathway in human middle ear epithelial cells. Hear Res209: 24-31. [PMID:16139976]

15. Clarke LL, Harline MC, Gawenis LR, Walker NM, Turner JT, Weisman GA. (2000) Extracellular UTP stimulates electrogenic bicarbonate secretion across CFTR knockout gallbladder epithelium. Am. J. Physiol. Gastrointest. Liver Physiol.279 (1): G132-8. [PMID:10898755]

16. Coutinho-Silva R, Ojcius DM, Gorecki DC, Persechini PM, Bisaggio RC, Mendes AN, Marks J, Burnstock G, Dunn PM. (2005) Multiple P2X and P2Y receptor subtypes in mouse J774, spleen and peritoneal macrophages. Biochem Pharmacol69: 641-655. [PMID:15670583]

17. Cressman VL, Lazarowski E, Homolya L, Boucher RC, Koller BH, Grubb BR. (1999) Effect of loss of P2Y(2) receptor gene expression on nucleotide regulation of murine epithelial Cl(-) transport. J Biol Chem274: 26461-26468. [PMID:10473606]

18. Davenport RJ, Diaz P, Galvin FC, Lloyd S, Mack SR, Owens R, Sabin V, Wynn J. (2007) Novel nucleotide triphosphates as potent P2Y2 agonists with enhanced stability over UTP. Bioorg Med Chem Lett17: 558-561. [PMID:17079144]

19. Davis CW, Lazarowski E. (2008) Coupling of airway ciliary activity and mucin secretion to mechanical stresses by purinergic signaling. Respiratory physiology & neurobiology163 (1-3): 208-213. [PMID:18635403]

20. Degagné E, Grbic DM, Dupuis AA, Lavoie EG, Langlois C, Jain N, Weisman GA, Sévigny J, Gendron FP. (2009) P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells. J. Immunol.183 (7): 4521-9. [PMID:19734210]

21. Deterding R, Retsch-Bogart G, Milgram L, Gibson R, Daines C, Zeitlin PL, Milla C, Marshall B, Lavange L, Engels J, Mathews D, Gorden J, Schaberg A, Williams J, Ramsey B. (2005) Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis. Pediatr Pulmonol39: 339-348. [PMID:15704203]

22. Dixon CJ, Bowler WB, Littlewood-Evans A, Dillon JP, Bilbe G, Sharpe GR, Gallagher JA. (1999) Regulation of epidermal homeostasis through P2Y2 receptors. Br J Pharmacol127: 1680-1686. [PMID:10455326]

23. El-Tayeb A, Qi A, Müller CE. (2006) Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors. J Med Chem.49: 7076-7087. [PMID:17125260]

24. El-Tayeb A, Qi A, Nicholas RA, Müller CE. (2011) Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors. J. Med. Chem.54 (8): 2878-90. [PMID:21417463]

25. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P et al.. (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature461 (7261): 282-6. [PMID:19741708]

26. Erb L, Lustig KD, Sullivan DM, Turner JT, Weisman GA. (1993) Functional expression and photoaffinity labelling of a cloned P2U purinergic receptor. Proc. Natl. Acad. Sci. U.S.A.90: 10449-10453. [PMID:8248130]

27. Gödecke S, Decking UK, Gödecke A, Schrader J. (1996) Cloning of the rat P2u receptor and its potential role in coronary vasodilation. Am. J. Physiol.270: C570-C577. [PMID:8779921]

28. Gallagher CJ, Salter MW. (2003) Differential properties of astrocyte calcium waves mediated by P2Y1 and P2Y2 receptors. J Neurosci23: 6728-6839. [PMID:12890765]

29. Gayle S, Burnstock G. (2005) Immunolocalisation of P2X and P2Y nucleotide receptors in the rat nasal mucosa. Cell Tissue Res319: 27-36. [PMID:15558320]

30. Geary C, Akinbi H, Korfhagen T, Fabre JE, Boucher R, Rice W. (2005) Increased susceptibility of purinergic receptor-deficient mice to lung infection with Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol Physiol289: 890-895. [PMID:16024720]

31. Ghanem E, Robaye B, Leal T, Leipziger J, Van Driessche W, Beauwens R, Boeynaems JM. (2005) The role of epithelial P2Y(2) and P2Y(4) receptors in the regulation of intestinal chloride secretion. Br J Pharmacol, : -. [PMID:16056234]

32. Guns PJ, Van Assche T, Fransen PRobaye Boeynaems JM, Bult H. (2006) Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice. Br J Pharmacol147: 569-574. [PMID:16415908]

33. Homolya L, Watt WC, Lazarowski ER, Koller BH, Boucher RC. (1999) Nucleotide-regulated calcium signaling in lung fibroblasts and epithelial cells from normal and P2Y(2) receptor (-/-) mice. J Biol Chem274: 26454-26460. [PMID:10473605]

34. Ivanov AA, Ko H, Cosyn L, Maddileti S, Besada P, Fricks I, Costanzi S, Harden TK, Calenbergh SV, Jacobson KA. (2007) Molecular modeling of the human P2Y2 receptor and design of a selective agonist, 2'-amino-2'-deoxy-2-thiouridine 5'-triphosphate. J Med Chem50: 1166-1176. [PMID:17302398]

35. Janssens R, Paindavoine P, Parmentier M, Boeynaems JM. (1999) Human P2Y2 receptor polymorphism: identification and pharmacological characterization of two allelic variants. Br J Pharmacology127: 709-716. [PMID:10401562]

36. Kemp PA, Sugar RA, Jackson AD. (2004) Nucleotide-mediated mucin secretion from differentiated human bronchial epithelial cells. Am. J. Respir. Cell Mol. Biol.31 (4): 446-55. [PMID:15231488]

37. Kim HJ, Ajit D, Peterson TS, Wang Y, Camden JM, Gibson Wood W, Sun GY, Erb L, Petris M, Weisman GA. (2012) Nucleotides released from Aβ₁₋₄₂ -treated microglial cells increase cell migration and Aβ₁₋₄₂ uptake through P2Y₂ receptor activation. J. Neurochem.121 (2): 228-38. [PMID:22353164]

38. Kim HS, Ravi RG, Marquez VE, Maddileti S, Wihlborg AK, Erlinge D, Malmsjo M, Boyer JL, Harden TK, Jacobson KA. (2002) Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors. J Med Chem45: 208-218. [PMID:11754592]

39. Kishore BK, Krane CM, Miller RL, Shi H, Zhang P, Hemmert A, Sun R, Nelson RD. (2005) P2Y2 receptor mRNA and protein expression is altered in inner medullas of hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function. Am J Physiol Renal Physiol.288: 1164-1172. [PMID:15687250]

40. Ko H, Carter RL, Cosyn L, Petrelli R, de Castro S, Besada P, Zhou Y, Cappellacci L, Franchetti P, Grifantini M, Van Calenbergh S, Harden TK, Jacobson KA. (2008) Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorg Med Chem16: 6319-6332. [PMID:18514530]

41. Kobayashi K, Fukuoka T, Yamanaka H, Dai Y, Obata K, Tokunaga A, Noguchi K. (2006) Neurons and glial cells differentially express P2Y receptor mRNAs in the rat dorsal root ganglion and spinal cord. J Comp Neurol498: 443-454. [PMID:16874807]

42. Kong Q, Peterson TS, Baker O, Stanley E, Camden J, Seye CI, Erb L, Simonyi A, Wood WG, Sun GY et al.. (2009) Interleukin-1beta enhances nucleotide-induced and alpha-secretase-dependent amyloid precursor protein processing in rat primary cortical neurons via up-regulation of the P2Y(2) receptor. J. Neurochem.109 (5): 1300-10. [PMID:19317852]

43. Kotevic I, Kirschner KM, Porzig H, Baltensperger K. (2005) Constitutive interaction of the P2Y2 receptor with the hematopoietic cell-specific G protein G(alpha16) and evidence for receptor oligomers. Cell Signal17: 869-880. [PMID:15763429]

44. Krzeminski P, Misiewicz I, Pomorski P, Kasprzycka-Guttman T, Baranska J. (2007) Mitochondrial localization of P2Y1, P2Y2 and P2Y12 receptors in rat astrocytes and glioma C6 cells. Brain Res Bull71: 587-592. [PMID:17292801]

45. Kunzelmann K, Bachhuber T, Regeer R, Markovich D, Sun J, Schreiber R. (2005) Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2. FASEB J19: 142-143. [PMID:15504951]

46. Lazarowski ER, Watt WC, Stutts MJ, Boucher RC, Harden TK. (1995) Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate. Br. J. Pharmacol.116: 1619-1627. [PMID:8564228]

47. Lemon G, Brockhausen J, Li GH, Gibson WG, Bennett MR. (2005) Calcium mobilization and spontaneous transient outward current characteristics upon agonist activation of P2Y2 receptors in smooth muscle cells. Biophys J88: 1507-1523. [PMID:15556987]

48. Liao Z, Seye CI, Weisman GA, Erb L. (2007) The P2Y2 nucleotide receptor requires interaction with alpha v integrins to access and activate G12. J Cell Sci.120: 1654-1662. [PMID:17452627]

49. Liu J, Liao Z, Camden J, Griffin KD, Garrad RC, Santiago-Pérez LI, González FA, Seye CI, Weisman GA, Erb L. (2004) Src homology 3 binding sites in the P2Y2 nucleotide receptor interact with Src and regulate activities of Src, proline-rich tyrosine kinase 2, and growth factor receptors. J. Biol. Chem.279 (9): 8212-8. [PMID:14670955]

50. Lustig KD, Shiau AK, Brake AJ, Julius D. (1993) Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc. Natl. Acad. Sci. U.S.A.90: 5113-5117. [PMID:7685114]

51. Malin SA, Davis BM, Koerber HR, Reynolds IJ, Albers KM, Molliver DC. (2008) Thermal nociception and TRPV1 function are attenuated in mice lacking the nucleotide receptor P2Y2. Pain138: 484-496. [PMID:18343036]

52. Matos JE, Robaye B, Boeynaems JM, Beauwens R, Leipziger J. (2005) K+ secretion activated by luminal P2Y2 and P2Y4 receptors in mouse colon. J Physiol564: 269-279. [PMID:15718265]

53. Moore DJ, Chambers JK, Wahlin JP, Tan KB, Moore GB, Jenkins O, Emson PC, Murdock PR. (2001) Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study. Biochim Biophys Acta1521: 107-119. [PMID:11690642]

54. Mori T, Miyashita T, Akiyama K, Inamoto R, Mori N. (2009) The expression of P2Y1, 2, 4, and 6 receptors in rat endolymphatic sac epithelia. Neuroreport20: 419-423. [PMID:19223794]

55. Orriss IR, Utting JC, Brandao-Burch A, Colston K, Grubb BR, Burnstock G, Arnett TR. (2007) Extracellular nucleotides block bone mineralization in vitro: evidence for dual inhibitory mechanisms involving both P2Y2 receptors and pyrophosphate. Endocrinology148: 4208-4216. [PMID:17569759]

56. Parr CE, Sullivan DM, Paradiso AM, Lazarowski ER, Burch LH, Olsen JC, Erb L, Weisman GA, Boucher RC, Turner JT. (1994) Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy. Proc. Natl. Acad. Sci. U.S.A.91 (8): 3275-9. [PMID:8159738]

57. Patel K, Barnes A, Camacho J, Paterson C, Boughtflower R, Cousens D, Marshall F. (2001) Activity of diadenosine polyphosphates at P2Y receptors stably expressed in 1321N1 cells. Eur J Pharmacol430: 203-210. [PMID:11711032]

58. Pendergast W, Yerxa BR, Douglass JG, Shaver SR, Dougherty RW, Redick CC, Sims IF, Rideout JL. (2001) Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5'-polyphosphates. Bioorg Med Chem Lett11: 157-160. [PMID:11206448]

59. Pochynyuk O, Bugaj V, Rieg T, Insel PA, Mironova E, Vallon V, Stockand JD. (2008) Paracrine regulation of the epithelial Na+ channel in the mammalian collecting duct by purinergic P2Y2 receptor tone. J Biol Chem283: 36599-36607. [PMID:18981175]

60. Ratchford AM, Baker OJ, Camden JM, Rikka S, Petris MJ, Seye CI, Erb L, Weisman GA. (2010) P2Y2 nucleotide receptors mediate metalloprotease-dependent phosphorylation of epidermal growth factor receptor and ErbB3 in human salivary gland cells. J. Biol. Chem.285 (10): 7545-55. [PMID:20064929]

61. Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, Vallon V. (2007) Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J.21: 3717-3726. [PMID:17575258]

62. Rodrigues RJ, Almeida T, Richardson PJ, Oliveira CR, Cunha RA. (2005) Dual presynaptic control by ATP of glutamate release via facilitatory P2X1, P2X2/3, and P2X3 and inhibitory P2Y1, P2Y2, and/or P2Y4 receptors in the rat hippocampus. J Neurosci.25: 6286-6295. [PMID:16000618]

63. Sabala P, Czajkowski R, Przybylek K, Kalita K, Kaczmarek L, Baranska J. (2001) Two subtypes of G protein-coupled nucleotide receptors, P2Y(1) and P2Y(2) are involved in calcium signalling in glioma C6 cells. Br J Pharmacol132: 393-402. [PMID:11159687]

64. Santiago-Pérez LI, Flores RV, Santos-Berríos C, Chorna NE, Krugh B, Garrad RC, Erb L, Weisman GA, González FA. (2001) P2Y(2) nucleotide receptor signaling in human monocytic cells: activation, desensitization and coupling to mitogen-activated protein kinases. J. Cell. Physiol.187 (2): 196-208. [PMID:11267999]

65. Schachter JB, Harden TK. (1997) An examination of deoxyadenosine 5'(α-thio)triphosphate as a ligand to define P2Y receptors and its selectivity as a low potency partial agonist of the P2Y1receptor. Br. J. Pharmacol.121: 338-344. [PMID:9154346]

66. Schachter JB, Sromek SM, Nicholas RA, Harden TK. (1997) HEK293 human embryonic kidney cells endogenously express the P2Y1 and P2Y2 receptors. Neuropharmacology36: 1181-1187. [PMID:9364473]

67. Schrader AM, Camden JM, Weisman GA. (2005) P2Y2 nucleotide receptor up-regulation in submandibular gland cells from the NOD.B10 mouse model of Sjögren's syndrome. Arch. Oral Biol.50 (6): 533-40. [PMID:15848146]

68. Seye CI, Gadeau AP, Daret D, Dupuch F, Alzieu P, Capron L, Desgranges C. (1997) Overexpression of P2Y2 purinoceptor in intimal lesions of the rat aorta. Arterioscler Thromb Vasc Biol17: 3602-3610. [PMID:9437211]

69. Seye CI, Yu N, González FA, Erb L, Weisman GA. (2004) The P2Y2 nucleotide receptor mediates vascular cell adhesion molecule-1 expression through interaction with VEGF receptor-2 (KDR/Flk-1). J. Biol. Chem.279 (34): 35679-86. [PMID:15175347]

70. Sun R, Carlson NG, Hemmert AC, Kishore BK. (2005) P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function. Am J Physiol Renal Physiol289: 585-592. [PMID:15840771]

71. Sun R, Miller RL, Hemmert AC, Zhang P, Shi H, Nelson RD, Kishore BK. (2005) Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD. American journal of physiology. Renal physiology289 (4): 768-776. [PMID:15914777]

72. Taboubi S, Milanini J, Delamarre E, Parat F, Garrouste F, Pommier G, Takasaki J, Hubaud JC, Kovacic H, Lehmann M. (2007) G alpha(q/11)-coupled P2Y2 nucleotide receptor inhibits human keratinocyte spreading and migration. FASEB J21: 4047-4058. [PMID:17609252]

73. Weyler S, Baqi Y, Hillmann P, Kaulich M, Hunder AM, Müller IA, Müller CE. (2008) Combinatorial synthesis of anilinoanthraquinone derivatives and evaluation as non-nucleotide-derived P2Y2 receptor antagonists. Bioorg Med Chem Lett18: 223-227. [PMID:18006312]

74. Wihlborg AK, Balogh J, Wang L, Borna C, Dou Y, Joshi BV, Lazarowski E, Jacobson KA, Arner A, Erlinge D. (2006) Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y2 and P2Y6 receptors on cardiomyocytes and release of UTP in man during myocardial infarction. Circ Res98: 970-976. [PMID:16543499]

75. Wong AM, Chow AW, Au SC, Wong CC, Ko WH. (2008) Apical vs. Basolateral P2Y6 Receptor-mediated Cl- Secretion in Immortalized Bronchial Epithelia. Am J Respir Cell Mol Biol40: 733-745. [PMID:19011163]

76. Yamamoto S, Ichishima K, Ehara T. (2007) Regulation of extracellular UTP-activated Cl- current by P2Y-PLC-PKC signaling and ATP hydrolysis in mouse ventricular myocytes. J Physiol Sci57: 85-94. [PMID:17291397]

77. Yerxa BR, Sabater JR, Davis CW, Stutts MJ, Lang-Furr M, Picher M, Jones AC, Cowlen M, Dougherty R, Boyer J, Abraham WM, Boucher RC. (2002) Pharmacology of INS37217 [P(1)-(uridine 5')-P(4)- (2'-deoxycytidine 5')tetraphosphate, tetrasodium salt], a next-generation P2Y(2) receptor agonist for the treatment of cystic fibrosis. J Pharmacol Exp Ther302: 871-880. [PMID:12183642]

78. Yu N, Erb L, Shivaji R, Weisman GA, Seye CI. (2008) Binding of the P2Y2 nucleotide receptor to filamin A regulates migration of vascular smooth muscle cells. Circ Res102: 581-588. [PMID:18202316]

79. Zhang Y, Pop IL, Carlson NG, Kishore BK. (2012) Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling. Am. J. Physiol. Renal Physiol.302 (1): F70-7. [PMID:21975874]

80. Zhang Y, Sands JM, Kohan DE, Nelson RD, Martin CF, Carlson NG, Kamerath CD, Ge Y, Klein JD, Kishore BK. (2008) Potential role of purinergic signaling in urinary concentration in inner medulla: insights from P2Y2 receptor gene knockout mice. Am J Physiol Renal Physiol, : 1715-1724. [PMID:18829742]

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: P2Y2 receptor. Last modified on 13/08/2013. Accessed on 27/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=324.

Contact us | Print | Back to top | Help
Copyright © 2014 IUPHAR