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P2Y6 receptor

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Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 326

Nomenclature: P2Y6 receptor

Family: P2Y receptors

Annotation status:  image of a blue circle Annotated and reviewed, awaiting update  » Email us

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 7 328 11q13.4 P2RY6 pyrimidinergic receptor P2Y6 7,26
Mouse 7 328 7 E2 P2ry6 pyrimidinergic receptor P2Y, G-protein coupled, 6 25
Rat 7 328 1q32 P2ry6 pyrimidinergic receptor P2Y6 1
Previous and Unofficial Names Click here for help
uridine nucleotide receptor | P2Y6 | P2Y ATP receptor 6 | P2Y purinoceptor 6 | pyrimidinergic receptor P2Y
Database Links Click here for help
Specialist databases
GPCRdb p2ry6_human (Hs), p2ry6_mouse (Mm), p2ry6_rat (Rn)
Other databases
Alphafold Q15077 (Hs), Q9ERK9 (Mm), Q63371 (Rn)
ChEMBL Target CHEMBL4714 (Hs), CHEMBL3543 (Rn)
Ensembl Gene ENSG00000171631 (Hs), ENSMUSG00000048779 (Mm), ENSRNOG00000019270 (Rn)
Entrez Gene 5031 (Hs), 233571 (Mm), 117264 (Rn)
Human Protein Atlas ENSG00000171631 (Hs)
KEGG Gene hsa:5031 (Hs), mmu:233571 (Mm), rno:117264 (Rn)
OMIM 602451 (Hs)
Pharos Q15077 (Hs)
RefSeq Nucleotide NM_001277204 (Hs), NM_183168 (Mm), NM_057124 (Rn)
RefSeq Protein NP_001264133 (Hs), NP_898991 (Mm), NP_476465 (Rn)
UniProtKB Q15077 (Hs), Q9ERK9 (Mm), Q63371 (Rn)
Wikipedia P2RY6 (Hs)
Natural/Endogenous Ligands Click here for help
UDP
UTP
Potency order of endogenous ligands (Human)
UDP >> UTP > ADP

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
Rp-5-OMe-UDPαB Small molecule or natural product Hs Agonist 8.1 pEC50 13,16
⤷ pEC50 8.1 (EC50 8x10-9 M) [13,16]
MRS2957 Small molecule or natural product Hs Agonist 7.9 pEC50 32
⤷ pEC50 7.9 (EC50 1.2x10-8 M) [32]
MRS2693 Small molecule or natural product Hs Full agonist 7.8 pEC50 3
⤷ pEC50 7.8 (EC50 1.5x10-8 M) [3]
MRS4162-BODIPY conjugate Small molecule or natural product Ligand is labelled Hs Agonist 7.6 pEC50 19
⤷ pEC50 7.6 (EC50 2.3x10-8 M) [19]
UDP-β-S Small molecule or natural product Hs Full agonist 7.6 pEC50 4
⤷ pEC50 7.6 [4]
3-phenacyl-UDP Small molecule or natural product Hs Full agonist 7.2 pEC50 10
⤷ pEC50 7.2 [10]
INS48823 Small molecule or natural product Hs Full agonist 6.9 pEC50 4
⤷ pEC50 6.9 [4]
Up3U Small molecule or natural product Hs Full agonist 6.7 pEC50 4
⤷ pEC50 6.7 [4]
UDP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 6.5 pEC50 7
⤷ pEC50 6.5 [7]
MRS2782 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 6.2 pEC50 21
⤷ pEC50 6.2 [21]
5BrUTP Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 6.1 pEC50 7
⤷ pEC50 6.1 [7]
UTP Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 5.2 pEC50 7
⤷ pEC50 5.2 [7]
ADP Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 4.5 pEC50 7
⤷ pEC50 4.5 [7]
2MeSATP Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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 [23].

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 Value Parameter Reference
reactive blue-2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKB 49
⤷ pKB 6.0 (KB 1x10-6 M) [49]
PPADS Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.0 pKB 49
⤷ pKB 4.0 (KB 1x10-4 M) [49]
suramin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.0 pKB 49
⤷ pKB 4.0 (KB 1x10-4 M) [49]
MRS2578 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 7.4 pIC50 29
⤷ pIC50 7.4 [29]
MRS2567 Small molecule or natural product Rn Antagonist 7.0 pIC50 29
⤷ pIC50 7.0 [29]
MRS2578 Small molecule or natural product Immunopharmacology Ligand Rn Antagonist 7.0 pIC50 29
⤷ pIC50 7.0 [29]
MRS2567 Small molecule or natural product Hs Antagonist 6.9 pIC50 29
⤷ pIC50 6.9 [29]
MRS4841 Small molecule or natural product Hs Antagonist 5.5 pIC50 38
⤷ pIC50 5.5 (IC50 2.99x10-6 M) [38]
Description: Determined as inhibition of UDP-induced Ca2+ mobilization in hP2Y6R-expressing 1321N1 astrocytoma cells
TIM-38 Small molecule or natural product Hs Antagonist 5.4 pIC50 18
⤷ pIC50 5.4 (IC50 4.3x10-6 M) [18]
Description: Antagonism of UDP-induced [Ca2+]i elevation via P2Y6
MRS4841 Small molecule or natural product Mm Antagonist 4.8 pIC50 38
⤷ pIC50 4.8 (IC50 1.78x10-5 M) [38]
reactive blue-2 Small molecule or natural product Click here for species-specific activity table 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 [29]. In 1321N1 cells transfected with the human P2Y6receptor, cysLT1 antagonists were demonstrated to inhibit UDP-mediated PLC activation (pIC50 <6)[28]
Immunopharmacology Comments
P2Y6R expression on airway epithelial cells is up-regulated during acute and chronic allergic airway inflammation, and selective antagonism of P2Y6R reduces typical features of experimental asthma [48]. The P2Y6 antagonist MRS2578 has been used to show P2Y6 purinergic signaling is involved in neutrophil activation (and possibly migration) and neutrophil extracellular trap (NET) formation [33] in the inflammatory response to gout-associated monosodium urate crystals [46].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References: 
Secondary Transduction Mechanisms Click here for help
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) [36].
References:  36,52
Tissue Distribution Click here for help
Cardiomyocytes
Species:  Human
Technique:  Real-time PCR
References:  51
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:  34
Placenta, skeletal muscle > brain, heart, liver, pancreas.
Species:  Human
Technique:  Northern blotting.
References:  26
Bone.
Species:  Human
Technique:  RT-PCR.
References:  26
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:  34
Spleen > placenta > lung, thymus, small intestine, blood leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  7
Bronchial epithelium
Species:  Human
Technique:  Real-time PCR
References:  52
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:  41
Bone marrow stromal cells
Species:  Human
Technique:  RT-PCR and Western blotting
References:  37,54
Atherosclerotic plaques in aorta
Species:  Mouse
Technique:  RT-PCR
References:  15
Gallbladder.
Species:  Mouse
Technique:  in situ hybridisation.
References:  25
Skeletal muscle
Species:  Mouse
Technique:  RT-PCR and Western blotting, immunofluorescence
References:  6
Microvascular endothelial cells
Species:  Mouse
Technique:  RT-PCR and Western blotting, immunofluorescence
References:  41
Isolated pancreatic islets and purified beta-cells
Species:  Mouse
Technique:  Real-time PCR
References:  40
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
Endolymphatic sac epithelia
Species:  Rat
Technique:  RT-PCR
References:  35
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 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:  7,25
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:  25
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 Click here for help
Contraction of smooth muscle.
Species:  Human
Tissue:  Cerebral arteries.
References:  27
NaCl secretion mediated via an increase in [Ca2+] and cAMP.
Species:  Rat
Tissue:  Basolateral membrane of colonic epithelium.
References:  24
DNA synthesis.
Species:  Rat
Tissue:  Aorta smooth muscle cells.
References:  17
Interleukin-8 release.
Species:  Human
Tissue:  THP-1 monocyte cells.
References:  50
Cl- secretion.
Species:  Mouse
Tissue:  Trachea.
References:  44
Proliferation of tumour cells.
Species:  Human
Tissue:  Lung epithelial tumour cells.
References:  43
Modulation of microglial phagocytosis
Species:  Rat
Tissue:  Brain
References:  22
Modulation of insulin and glucagone secretion
Species:  Mouse
Tissue:  Isolated pancreatic islets and purified β-cells
References:  40
Cross-talk with complement component 5a (C5a) in modulating calcium release from intracellular stores, through PLCβ3
Species:  Mouse
Tissue:  Macrophages
References:  42
Protection from apoptosis both in vitro and in vivo
Species:  Mouse
Tissue:  Skeletal muscle
References:  30
Positive inotropic effect
Species:  Mouse
Tissue:  Cardiomyocytes
References:  51
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:  52
Increased expression and release of CCL2
Species:  Mouse
Tissue:  Macrophages
References:  53
Increased expression of CCL2 and CCL3
Species:  Rat
Tissue:  Microglia
References:  20
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:  36
Inhibition of IFN-α production and induction of immune tolerance
Species:  Human
Tissue:  Plasmacytoid dendritic cells
References:  31,45
Release of IL-1, IL-6 and IL-8 in response to urate crystals
Species:  Human
Tissue:  Keratinocytes
References:  47
Physiological Consequences of Altering Gene Expression Click here for help
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 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:  48
P2Y6 knock-out mice exhibit attenuated inflammatory responses during LPS-induced vascular inflammation
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  41
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:  39
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 [21].

References

Show »

1. Bailey MA, Imbert-Teboul M, Turner C, Srai SK, Burnstock G, Unwin RJ. (2001) Evidence for basolateral P2Y(6) receptors along the rat proximal tubule: functional and molecular characterization. J Am Soc Nephrol, 12 (8): 1640-7. [PMID:11461936]

2. Bar I, Guns PJ, Metallo J, Cammarata D, Wilkin F, Boeynams JM, Bult H, Robaye B. (2008) Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. Mol Pharmacol, 74 (3): 777-84. [PMID:18523137]

3. Besada P, Shin DH, Costanzi S, Ko H, Mathé C, Gagneron J, Gosselin G, Maddileti S, Harden TK, Jacobson KA. (2006) Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor. J Med Chem, 49 (18): 5532-43. [PMID:16942026]

4. Brunschweiger A, Müller CE. (2006) P2 receptors activated by uracil nucleotides--an update. Curr Med Chem, 13 (3): 289-312. [PMID:16475938]

5. Ceruti S, Fumagalli M, Villa G, Verderio C, Abbracchio MP. (2008) Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium, 43 (6): 576-90. [PMID:18031810]

6. Chen D, Wang W, Guo W, Yu Q, Burnstock G, He C, Xiang Z, Zheng H. (2011) Expression of P2Y(6) receptors in the developing mouse skeletal muscle and after injury and repair. J Anat, 218 (6): 643-51. [PMID:21413988]

7. Communi D, Parmentier M, Boeynaems JM. (1996) Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem Biophys Res Commun, 222 (2): 303-8. [PMID:8670200]

8. Costanzi S, Joshi BV, Maddileti S, Mamedova L, Gonzalez-Moa MJ, Marquez VE, Harden TK, Jacobson KA. (2005) Human P2Y(6) receptor: molecular modeling leads to the rational design of a novel agonist based on a unique conformational preference. J Med Chem, 48 (26): 8108-11. [PMID:16366591]

9. Coutinho-Silva R, Ojcius DM, Górecki 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 Pharmacol, 69 (4): 641-55. [PMID:15670583]

10. 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 (24): 7076-87. [PMID:17125260]

11. Fries JE, Goczalik IM, Wheeler-Schilling TH, Kohler K, Guenther E, Wolf S, Wiedemann P, Bringmann A, Reichenbach A, Francke M et al.. (2005) Identification of P2Y receptor subtypes in human muller glial cells by physiology, single cell RT-PCR, and immunohistochemistry. Invest Ophthalmol Vis Sci, 46 (8): 3000-7. [PMID:16043877]

12. Giannattasio G, Ohta S, Boyce JR, Xing W, Balestrieri B, Boyce JA. (2011) The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonary inflammation. J Immunol, 187 (3): 1486-95. [PMID:21724990]

13. Ginsburg-Shmuel T, Haas M, Grbic D, Arguin G, Nadel Y, Gendron FP, Reiser G, Fischer B. (2012) UDP made a highly promising stable, potent, and selective P2Y6-receptor agonist upon introduction of a boranophosphate moiety. Bioorg Med Chem, 20 (18): 5483-95. [PMID:22901672]

14. Grbic DM, Degagné E, Langlois C, Dupuis AA, Gendron FP. (2008) Intestinal inflammation increases the expression of the P2Y6 receptor on epithelial cells and the release of CXC chemokine ligand 8 by UDP. J Immunol, 180 (4): 2659-68. [PMID:18250478]

15. Guns PJ, Hendrickx J, Van Assche T, Fransen P, Bult H. (2010) P2Y receptors and atherosclerosis in apolipoprotein E-deficient mice. Br J Pharmacol, 159 (2): 326-36. [PMID:20050854]

16. Haas M, Ginsburg-Shmuel T, Fischer B, Reiser G. (2014) 5-OMe-uridine-5'-O-(α-boranodiphosphate), a novel nucleotide derivative highly active at the human P2Y(6) receptor protects against death-receptor mediated glial apoptosis. Neurosci Lett, 578: 80-4. [PMID:24970757]

17. Hou M, Harden TK, Kuhn CM, Baldetorp B, Lazarowski E, Pendergast W, Möller S, Edvinsson L, Erlinge D. (2002) UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors. Am J Physiol Heart Circ Physiol, 282 (2): H784-92. [PMID:11788430]

18. Ito M, Egashira SI, Yoshida K, Mineno T, Kumagai K, Kojima H, Okabe T, Nagano T, Ui M, Matsuoka I. (2017) Identification of novel selective P2Y6 receptor antagonists by high-throughput screening assay. Life Sci, 180: 137-142. [PMID:28527783]

19. Jayasekara PS, Barrett MO, Ball CB, Brown KA, Hammes E, Balasubramanian R, Harden TK, Jacobson KA. (2014) 4-Alkyloxyimino derivatives of uridine-5'-triphosphate: distal modification of potent agonists as a strategy for molecular probes of P2Y2, P2Y4, and P2Y6 receptors. J Med Chem, 57 (9): 3874-83. [PMID:24712832]

20. Kim B, Jeong HK, Kim JH, Lee SY, Jou I, Joe EH. (2011) Uridine 5'-diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6 receptor. J Immunol, 186 (6): 3701-9. [PMID:21317391]

21. Ko H, Carter RL, Cosyn L, Petrelli R, de Castro S, Besada P, Zhou Y, Cappellacci L, Franchetti P, Grifantini M et al.. (2008) Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorg Med Chem, 16 (12): 6319-32. [PMID:18514530]

22. Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K. (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature, 446 (7139): 1091-5. [PMID:17410128]

23. Korcok J, Raimundo LN, Du X, Sims SM, Dixon SJ. (2005) P2Y6 nucleotide receptors activate NF-kappaB and increase survival of osteoclasts. J Biol Chem, 280 (17): 16909-15. [PMID:15722352]

24. Köttgen M, Löffler T, Jacobi C, Nitschke R, Pavenstädt H, Schreiber R, Frische S, Nielsen S, Leipziger J. (2003) P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport. J Clin Invest, 111 (3): 371-9. [PMID:12569163]

25. Lazarowski ER, Rochelle LG, O'Neal WK, Ribeiro CM, Grubb BR, Zhang V, Harden TK, Boucher RC. (2001) Cloning and functional characterization of two murine uridine nucleotide receptors reveal a potential target for correcting ion transport deficiency in cystic fibrosis gallbladder. J Pharmacol Exp Ther, 297 (1): 43-9. [PMID:11259526]

26. Maier R, Glatz A, Mosbacher J, Bilbe G. (1997) Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues. Biochem Biophys Res Commun, 240 (2): 298-302. [PMID:9412455]

27. Malmsjö M, Hou M, Pendergast W, Erlinge D, Edvinsson L. (2003) Potent P2Y6 receptor mediated contractions in human cerebral arteries. BMC Pharmacol, 3: 4. [PMID:12737633]

28. 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 Pharmacol, 71 (1-2): 115-25. [PMID:16280122]

29. Mamedova LK, Joshi BV, Gao ZG, von Kügelgen I, Jacobson KA. (2004) Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors. Biochem Pharmacol, 67 (9): 1763-70. [PMID:15081875]

30. Mamedova LK, Wang R, Besada P, Liang BT, Jacobson KA. (2008) Attenuation of apoptosis in vitro and ischemia/reperfusion injury in vivo in mouse skeletal muscle by P2Y6 receptor activation. Pharmacol Res, 58 (3-4): 232-9. [PMID:18805489]

31. Mao C, Wang S, Xiao Y, Xu J, Jiang Q, Jin M, Jiang X, Guo H, Ning G, Zhang Y. (2011) Impairment of regulatory capacity of CD4+CD25+ regulatory T cells mediated by dendritic cell polarization and hyperthyroidism in Graves' disease. J Immunol, 186 (8): 4734-43. [PMID:21398613]

32. Maruoka H, Barrett MO, Ko H, Tosh DK, Melman A, Burianek LE, Balasubramanian R, Berk B, Costanzi S, Harden TK et al.. (2010) Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5'-triphosphate gamma-ester modifications. J Med Chem, 53 (11): 4488-501. [PMID:20446735]

33. Maueröder C, Kienhöfer D, Hahn J, Schauer C, Manger B, Schett G, Herrmann M, Hoffmann MH. (2015) How neutrophil extracellular traps orchestrate the local immune response in gout. J Mol Med, 93 (7): 727-34. [PMID:26002146]

34. 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 Acta, 1521 (1-3): 107-19. [PMID:11690642]

35. 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. Neuroreport, 20 (4): 419-23. [PMID:19223794]

36. Nishida M, Sato Y, Uemura A, Narita Y, Tozaki-Saitoh H, Nakaya M, Ide T, Suzuki K, Inoue K, Nagao T et al.. (2008) P2Y6 receptor-Galpha12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis. EMBO J, 27 (23): 3104-15. [PMID:19008857]

37. Noronha-Matos JB, Costa MA, Magalhães-Cardoso MT, Ferreirinha F, Pelletier J, Freitas R, Neves JM, Sévigny J, Correia-de-Sá P. (2012) Role of ecto-NTPDases on UDP-sensitive P2Y(6) receptor activation during osteogenic differentiation of primary bone marrow stromal cells from postmenopausal women. J Cell Physiol, 227 (6): 2694-709. [PMID:21898410]

38. Oliva P, Pramanik A, Jung YH, Lewicki SA, Mwendwa JM, Park JH, Jacobson KA. (2024) Functionalized Congeners of 2H-Chromene P2Y6 Receptor Antagonists. Cells, 13 (16). [PMID:39195256]

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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.

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