Top ▲
Gene and Protein Information  |
||||||
| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 377 | 11q13.4 | P2RY2 | purinergic receptor P2Y2 | 60 |
| Mouse | 7 | 373 | 7 E2 | P2ry2 | purinergic receptor P2Y, G-protein coupled 2 | 54 |
| Rat | 7 | 374 | 1q32 | P2ry2 | purinergic receptor P2Y2 | 32,72 |
| Previous and Unofficial Names |
| ATP receptor | P2U purinoceptor 1 | P2Y ATP receptor 2 | P2Y purinoceptor 2 | purinergic receptor P2Y |
| Database Links |
|
| Specialist databases | |
| GPCRdb | p2ry2_human (Hs), p2ry2_mouse (Mm), p2ry2_rat (Rn) |
| Other databases | |
| Alphafold | P41231 (Hs), P35383 (Mm), P41232 (Rn) |
| ChEMBL Target | CHEMBL4398 (Hs), CHEMBL1075298 (Mm), CHEMBL4419 (Rn) |
| DrugBank Target | P41231 (Hs) |
| Ensembl Gene | ENSG00000175591 (Hs), ENSMUSG00000032860 (Mm), ENSRNOG00000019283 (Rn) |
| Entrez Gene | 5029 (Hs), 18442 (Mm), 29597 (Rn) |
| Human Protein Atlas | ENSG00000175591 (Hs) |
| KEGG Gene | hsa:5029 (Hs), mmu:18442 (Mm), rno:29597 (Rn) |
| OMIM | 600041 (Hs) |
| Pharos | P41231 (Hs) |
| RefSeq Nucleotide | NM_002564 (Hs), NM_008773 (Mm), NM_017255 (Rn) |
| RefSeq Protein | NP_002555 (Hs), NP_032799 (Mm), NP_058951 (Rn) |
| UniProtKB | P41231 (Hs), P35383 (Mm), P41232 (Rn) |
| Wikipedia | P2RY2 (Hs) |
| Natural/Endogenous Ligands |
| ATP |
| UTP |
| Potency order of endogenous ligands (Human) |
| UTP > ATP |
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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PSB1114 is a potent, selective P2Y2 agonist with >60-fold selectivity for versus P2Y4 and P2Y6 receptors [24]. Reference [49] EC50 values are found using IP3 functional assays. References [62,81] 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 [77]. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immuno Process Associations | ||
|
||
|
| 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 [21,30,80] | |
| References: 76,80 | |
| 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 [52]. Coupling of P2Y2 receptor to hematopoietic cell specific Gα16, belonging to the Gq family, was found in human erythroleukemia cells [46]. 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: 6,52 | |
| Tissue Distribution
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
| Expression Datasets |
|
|
| Functional Assays
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
| Physiological Functions
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
| Physiological Consequences of Altering Gene Expression
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
| Phenotypes, Alleles and Disease Models
|
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Biologically Significant Variants
|
||||||||
|
| General Comments |
| The three human transcript variants encode for the same 377 aa protein sequence [60]. P2Y2 receptors have been localized in mitochondria in rat astrocytes, C6 glioma cells and liver, suggesting their role in regulating mitochondrial calcium transport [8,47]. 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). |
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, Martínez-Torres A, Garay E. (2002) Ionic currents activated via purinergic receptors in the cumulus cell-enclosed mouse oocyte. Biol Reprod, 67 (3): 837-46. [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 USA, 102 (52): 19138-43. [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 Commun, 347 (3): 678-82. [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 Neurosci, 26 (14): 3798-804. [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 Chem, 280 (47): 39050-7. [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 ONE, 6 (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 Biochem, 99: 1165-1174. [PMID:16795051]
9. Brunschweiger A, Müller CE. (2006) P2 receptors activated by uracil nucleotides--an update. Curr Med Chem, 13 (3): 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 Genomics, 16 (3): 199-205. [PMID:16495779]
11. Camden JM, Schrader AM, Camden RE, González FA, Erb L, Seye CI, Weisman GA. (2005) P2Y2 nucleotide receptors enhance alpha-secretase-dependent amyloid precursor protein processing. J Biol Chem, 280 (19): 18696-702. [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. Science, 314 (5806): 1792-5. [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 Res, 209 (1-2): 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, 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]
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 Chem, 274 (37): 26461-8. [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 Lett, 17 (2): 558-61. [PMID:17079144]
19. Davis CW, Lazarowski E. (2008) Coupling of airway ciliary activity and mucin secretion to mechanical stresses by purinergic signaling. Respir Physiol Neurobiol, 163 (1-3): 208-13. [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 et al.. (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 Pulmonol, 39 (4): 339-48. [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 Pharmacol, 127 (7): 1680-6. [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 (24): 7076-87. [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. Nature, 461 (7261): 282-6. [PMID:19741708]
26. Erb L, Lustig KD, Sullivan DM, Turner JT, Weisman GA. (1993) Functional expression and photoaffinity labeling of a cloned P2U purinergic receptor. Proc Natl Acad Sci USA, 90 (22): 10449-53. [PMID:8248130]
27. Gallagher CJ, Salter MW. (2003) Differential properties of astrocyte calcium waves mediated by P2Y1 and P2Y2 receptors. J Neurosci, 23 (17): 6728-39. [PMID:12890765]
28. Gayle S, Burnstock G. (2005) Immunolocalisation of P2X and P2Y nucleotide receptors in the rat nasal mucosa. Cell Tissue Res, 319 (1): 27-36. [PMID:15558320]
29. 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 Physiol, 289 (5): L890-5. [PMID:16024720]
30. Ghanem E, Robaye B, Leal T, Leipziger J, Van Driessche W, Beauwens R, Boeynaems JM. (2005) The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion. Br J Pharmacol, 146 (3): 364-9. [PMID:16056234]
31. Guns PJ, Van Assche T, Fransen P, Robaye B, Boeynaems JM, Bult H. (2006) Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice. Br J Pharmacol, 147 (5): 569-74. [PMID:16415908]
32. 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 (2 Pt 1): C570-7. [PMID:8779921]
33. Hillmann P, Ko GY, Spinrath A, Raulf A, von Kügelgen I, Wolff SC, Nicholas RA, Kostenis E, Höltje HD, Müller CE. (2009) Key determinants of nucleotide-activated G protein-coupled P2Y(2) receptor function revealed by chemical and pharmacological experiments, mutagenesis and homology modeling. J Med Chem, 52 (9): 2762-75. [PMID:19419204]
34. 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 Chem, 274 (37): 26454-60. [PMID:10473605]
35. Ivanov AA, Fricks I, Kendall Harden T, Jacobson KA. (2007) Molecular dynamics simulation of the P2Y14 receptor. Ligand docking and identification of a putative binding site of the distal hexose moiety. Bioorg Med Chem Lett, 17: 761-766. [PMID:17088057]
36. 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 Chem, 50 (6): 1166-76. [PMID:17302398]
37. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem, 45 (19): 4057-93. [PMID:12213051]
38. Janssens R, Paindavoine P, Parmentier M, Boeynaems JM. (1999) Human P2Y2 receptor polymorphism: identification and pharmacological characterization of two allelic variants. Br J Pharmacol, 127 (3): 709-16. [PMID:10401562]
39. 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]
40. 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]
41. Kim HS, Ravi RG, Marquez VE, Maddileti S, Wihlborg AK, Erlinge D, Malmsjö 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 Chem, 45 (1): 208-18. [PMID:11754592]
42. 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 (6): F1164-72. [PMID:15687250]
43. 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]
44. Kobayashi K, Fukuoka T, Yamanaka H, Iyamanaka 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 Neurol, 498 (4): 443-54. [PMID:16874807]
45. 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]
46. 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 Signal, 17 (7): 869-80. [PMID:15763429]
47. Krzeminski P, Misiewicz I, Pomorski P, Kasprzycka-Guttman T, Barańska J, Brańska J. (2007) Mitochondrial localization of P2Y1, P2Y2 and P2Y12 receptors in rat astrocytes and glioma C6 cells. Brain Res Bull, 71 (6): 587-92. [PMID:17292801]
48. 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 J, 19 (1): 142-3. [PMID:15504951]
49. 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 (1): 1619-27. [PMID:8564228]
50. Lazarowski ER, Watt WC, Stutts MJ, Brown HA, Boucher RC, Harden TK. (1996) Enzymatic synthesis of UTP gamma S, a potent hydrolysis resistant agonist of P2U-purinoceptors. Br J Pharmacol, 117 (1): 203-9. [PMID:8825364]
51. 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 J, 88 (3): 1507-23. [PMID:15556987]
52. 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 (Pt 9): 1654-62. [PMID:17452627]
53. 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]
54. Lustig KD, Shiau AK, Brake AJ, Julius D. (1993) Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc Natl Acad Sci USA, 90 (11): 5113-7. [PMID:7685114]
55. 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. Pain, 138 (3): 484-96. [PMID:18343036]
56. Matos JE, Robaye B, Boeynaems JM, Beauwens R, Leipziger J. (2005) K+ secretion activated by luminal P2Y2 and P2Y4 receptors in mouse colon. J Physiol (Lond.), 564 (Pt 1): 269-79. [PMID:15718265]
57. 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]
58. 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]
59. 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. Endocrinology, 148 (9): 4208-16. [PMID:17569759]
60. 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 USA, 91 (8): 3275-9. [PMID:8159738]
61. 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 Pharmacol, 430 (2-3): 203-10. [PMID:11711032]
62. Pendergast W, Yerxa BR, Douglass 3rd 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 Lett, 11 (2): 157-60. [PMID:11206448]
63. 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 Chem, 283 (52): 36599-607. [PMID:18981175]
64. 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]
65. 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 (13): 3717-26. [PMID:17575258]
66. 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 (27): 6286-95. [PMID:16000618]
67. Sabala P, Czajkowski R, Przybyłek K, Kalita K, Kaczmarek L, Barańska 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 Pharmacol, 132 (2): 393-402. [PMID:11159687]
68. 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]
69. Schachter JB, Harden TK. (1997) An examination of deoxyadenosine 5'(alpha-thio)triphosphate as a ligand to define P2Y receptors and its selectivity as a low potency partial agonist of the P2Y1 receptor. Br J Pharmacol, 121 (2): 338-44. [PMID:9154346]
70. Schachter JB, Sromek SM, Nicholas RA, Harden TK. (1997) HEK293 human embryonic kidney cells endogenously express the P2Y1 and P2Y2 receptors. Neuropharmacology, 36 (9): 1181-7. [PMID:9364473]
71. 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]
72. 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 Biol, 17 (12): 3602-10. [PMID:9437211]
73. 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]
74. 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 Physiol, 289 (3): F585-92. [PMID:15840771]
75. 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. Am J Physiol Renal Physiol, 289 (4): F768-76. [PMID:15914777]
76. 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 J, 21 (14): 4047-58. [PMID:17609252]
77. 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 Lett, 18 (1): 223-7. [PMID:18006312]
78. 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 Res, 98 (7): 970-6. [PMID:16543499]
79. Wong AM, Chow AW, Au SC, Wong CC, Ko WH. (2009) Apical versus basolateral P2Y(6) receptor-mediated Cl(-) secretion in immortalized bronchial epithelia. Am J Respir Cell Mol Biol, 40 (6): 733-45. [PMID:19011163]
80. 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 Sci, 57 (2): 85-94. [PMID:17291397]
81. Yerxa BR, Sabater JR, Davis CW, Stutts MJ, Lang-Furr M, Picher M, Jones AC, Cowlen M, Dougherty R, Boyer J et al.. (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 Ther, 302 (3): 871-80. [PMID:12183642]
82. 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 Res, 102 (5): 581-8. [PMID:18202316]
83. 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]
84. 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, 295 (6): F1715-24. [PMID:18829742]
