Nomenclature: P2Y12 receptor

Family: P2Y receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 342 3q24-q25 P2RY12 purinergic receptor P2Y, G-protein coupled, 12 5,22
Mouse 7 347 3 D P2ry12 purinergic receptor P2Y, G-protein coupled 12 34
Rat 7 343 2q31 P2ry12 purinergic receptor P2Y, G-protein coupled, 12 22,38
Previous and Unofficial Names
P2T
P2YAC
P2TAC
P2Y?
P2Ycyc
SP1999
P2YADP
P2T
P2Y12
HORK3
P2Y purinoceptor 12
P2Y12 platelet ADP receptor
purinergic receptor P2Y, G-protein coupled 12
purinergic receptor P2Y, G-protein coupled, 12
2900079B22Rik
4921504D23Rik
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
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human P2Y12 receptor in complex with an antithrombotic drug
PDB Id:  4NTJ
Ligand:  AZD1283
Resolution:  2.62Å
Species:  Human
References:  45
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of P2Y12 receptor in complex with 2MeSATP
PDB Id:  4PY0
Ligand:  2MeSATP
Resolution:  3.1Å
Species:  Human
References:  44
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of P2Y12 receptor in complex with 2MeSADP
PDB Id:  4PXZ
Ligand:  2MeSADP
Resolution:  2.5Å
Species:  Human
References:  44
Natural/Endogenous Ligands
ADP
ATP
Rank order of potency (Human)
ADP>>ATP
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
2MeSADP Hs Full agonist 9.2 pKi 20
pKi 9.2 [20]
2MeSATP Hs Full agonist 8.7 pKi 20
pKi 8.7 [20]
ADP Hs Full agonist 5.9 pKi 20
pKi 5.9 [20]
ATPγS Hs Full agonist 5.5 pKi 20
pKi 5.5 [20]
ATP Hs Full agonist 5.2 pKi 20
pKi 5.2 [20]
ADPβS Hs Full agonist 8.6 pIC50 40
pIC50 8.6 [40]
[3H]2MeSADP Hs Full agonist 7.5 – 9.6 pIC50 40
pIC50 7.5 – 9.6 (IC50 2.5x10-10 – 3.16x10-8 M) [40]
Agonist Comments
An in silico screening for endogenous ligands acting on the human P2Y12 receptor revealed cysteinylleukotrienes (CysLTs) and 5-phosphoribosyl 1-pyrophosphate (PRPP) as potential ligands, in addition to the already known P2Y12 ligands such as 2MeSADP and ADP. In CHO cells stably expressing P2Y12-Gα16 fusion proteins, CysLTE4 and PRPP acted on the P2Y12 receptor as agonists with EC50 values of 1.3 and 7.8 nM, respectively [31].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PSB-0739 Hs Antagonist 9.8 pA2 21
pA2 9.8 [21]
[3H]PSB-0413 Hs Antagonist 8.3 – 8.5 pKd 12,32
pKd 8.3 – 8.5 (Kd 3.16x10-9 – 4.57x10-9 M) [12,32]
AR-C67085 Hs Antagonist 8.2 pKd 27
pKd 8.2 [27]
compound 20o [PMID:22984835] Hs Antagonist 8.1 pKi 43
pKi 8.1 (Ki 7.7x10-9 M) [43]
PSB-0739 Hs Antagonist 7.6 pKi 2
pKi 7.6 (Ki 2.49x10-8 M) [2]
clopidogrel (active metabolite) Hs Antagonist 6.9 pKi 20
pKi 6.9 [20]
compound 4 [PMID:22984835] Hs Antagonist 6.9 pKi 43
pKi 6.9 (Ki 1.39x10-7 M) [43]
pCMPS Hs Antagonist 5.9 pKi 20
pKi 5.9 [20]
cangrelor Hs Antagonist 8.0 – 9.4 pIC50 25,40
pIC50 9.4 (IC50 4x10-10 M) [25]
pIC50 8.0 [40]
INS50589 Hs Antagonist 7.95 pIC50 11
pIC50 7.95 [11]
ARL66096 Hs Antagonist 7.95 pIC50 23-24
pIC50 7.95 [23-24]
BX 667 Hs Antagonist 7.0 pIC50 35
pIC50 7.0 [35]
compound 4 [PMID:23083103] Hs Antagonist 6.9 pIC50 10
pIC50 6.9 [10]
BX 048 Hs Antagonist 6.5 pIC50 35
pIC50 6.5 [35]
INS49266 Hs Antagonist 6.28 pIC50 11
pIC50 6.28 [11]
2MeSAMP Hs Antagonist 5.4 pIC50 40
pIC50 5.4 [40]
R-138727 Hs Antagonist 4.7 – 5.7 pIC50 18
pIC50 4.7 – 5.7 [18]
Antagonist Comments
A recent paper analysed the molecular mechanisms by which 2MeSAMP and Cangrelor (ARC69931MX), two widely used P2Y12 antagonists, inhibit human platelet activation. 2MeSAMP and ARC69931MX interacted with an unidentified platelet G protein-coupled receptor inducing cAMP-mediated inhibition of platelet function. This inhibition is in addition to that derived from antagonism of P2Y16 receptors [39]. PRT060128 is a patented high affinity antagonist [17].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
ticagrelor Hs Negative 7.85 pKi 43
pKi 7.85 (Ki 1.4x10-8 M) [43]
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  38
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Other - See Comments
Comments:  The intracellular pathways through which P2Y12 amplifies platelet responses include inhibition of cyclic AMP production, vasodilator-stimulated phosphoprotein (VASP) dephosphorylation, phosphoinositide 3 kinase (PI 3-K) and small GTPase Rap1b activation [16,37]. In some experimental systems, P2Y12/P2Y13 receptors were found to be coupled to [Ca2+]i increases. In particular, in microglial and satellite glial cells from trigeminal ganglia, the ADP-induced [Ca2+]i responses were significantly reduced after pretreatement with Cangrelor, an antagonist selective for P2Y12 and P2Y13, thus suggesting their activation may also contribute to ADP-mediated effects [4,9].
References: 
Tissue Distribution
Platelets and brain tissues.
Species:  Human
Technique:  Northern blotting.
References:  22
Vascular smooth muscle cells
Species:  Human
Technique:  real-time PCR
References:  42
Brain, heart, spleen, lung, liver and macrophages.
Species:  Rat
Technique:  Northern blotting.
References:  36
Brain (in particular glial cells).
Species:  Rat
Technique:  In situ hybridisation and immunocytochemistry.
References:  36
Spinal cord microglia
Species:  Rat
Technique:  Immunohistochemistry
References:  28
Epithelial cells lining intrahepatic bile ducts (cholangiocytes)
Species:  Rat
Technique:  RT-PCR, western blot
References:  29
Expression Datasets

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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
Measurement of IP levels in COS-7 cells transfected with the human P2Y12 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  IP accumulation.
References:  5
Measurement of cAMP levels in 1321N1 cells transfected with the rat P2Y12 receptor.
Species:  Rat
Tissue:  1321N1 cells.
Response measured:  Inhibition of cAMP accumulation (PTX-sensitive).
References:  38
Measurement of K+ current using patch-clamping of SCG cells transfected with the P2Y12 receptor and GIRK1 and GIRK2 channels.
Species:  Rat
Tissue:  SCG neurons.
Response measured:  Near-stable activation of GIRK.
References:  38
Measurement of Ca2+ current in SCG neurons transfected with the rat P2Y12 receptor and endogenously expressing N-type Ca2+ channels.
Species:  Rat
Tissue:  SCG neurons.
Response measured:  Inhibition of ICa(N).
References:  38
Measurement of cAMP levels in CHO cells transfected with the human P2Y12 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  22
Measurement of VASP phosphorylation in human platelets endogenously expressing the P2Y12 receptor.
Species:  Human
Tissue:  Platelets.
Response measured:  Inhibition of cAMP-dependent PKA activity.
References:  3
Measurement of cAMP levels in human platelets endogenously expressing the P2Y12 receptor.
Species:  Human
Tissue:  Platelets
Response measured:  inhibition of PGE1-induced platelet cAMP accumulation
References:  7
Physiological Functions
Role in the vessel wall response to arterial injury and thrombosis
Species:  Mouse
Tissue:  Platelets
References:  13
Role in sustaining platelet aggregation and in promoting thrombus growth and stabilization. Role in dense and alpha granule secretion, P-selectin expression and microparticle formation.
Species:  Human
Tissue:  Platelets
References:  16,26
Role in microglial chemotaxis
Species:  Mouse
Tissue:  hippocampal tissue slices
References:  19,33
Physiological Consequences of Altering Gene Expression
P2Y12 receptor knockout mice show impaired platelet activation/adhesion in in vivo mesenteric arteries when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  1
Microglia in P2Y12 knock-out mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  19
In spinal microglia, after partial sciatic nerve transection, antisense knockdown of P2Y12 expression suppressed the development of pain behaviors.
Species:  Rat
Tissue: 
Technique:  Antisense oligonucleotide
References:  28
Mice lacking P2Y12 displayed impaired tactile allodynia after nerve injury
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  41
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
P2ry12tm1Pcon P2ry12tm1Pcon/P2ry12tm1Pcon
involves: 129P2/OlaHsd * C57BL/6
MGI:1918089  MP:0002551 abnormal blood coagulation PMID: 12897207 
P2ry12tm1Pcon P2ry12tm1Pcon/P2ry12tm1Pcon
involves: 129P2/OlaHsd * C57BL/6
MGI:1918089  MP:0005464 abnormal platelet physiology PMID: 12897207 
P2ry12tm1Pcon P2ry12tm1Pcon/P2ry12tm1Pcon
involves: 129P2/OlaHsd * C57BL/6
MGI:1918089  MP:0009549 decreased platelet aggregation PMID: 12897207 
P2ry12tm1Cjf P2ry12tm1Cjf/P2ry12tm1Cjf
involves: 129/Sv
MGI:1918089  MP:0009549 decreased platelet aggregation PMID: 11413167 
P2ry12tm1Pcon P2ry12tm1Pcon/P2ry12tm1Pcon
involves: 129P2/OlaHsd * C57BL/6
MGI:1918089  MP:0005606 increased bleeding time PMID: 12897207 
P2ry12tm1Cjf P2ry12tm1Cjf/P2ry12tm1Cjf
involves: 129/Sv
MGI:1918089  MP:0005606 increased bleeding time PMID: 11413167 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Platelet-type bleeding disorder
OMIM:  609821
Orphanet:  36355
Comments: 
References:  6-7
Click column headers to sort
Type Species Molecular location Description Reference
single nucleotide polymorphism Human R256Q 6-7
single nucleotide polymorphism Human R265W 6-7
Biologically Significant Variants
Type:  Naturally occuring mutations
Species:  Human
Description:  A group of single nucleotide polymorphisms in the P2Y12 gene, forming the so called P2Y12 H2 haplotype, has been associated with increased platelet responsiveness to ADP, increased risk of pheripheral arterial disease and with coronary artery disease.
References:  8,14-15,46
General Comments
Clopidogrel has a well-established role as an antithrombotic agent in the settings of percutaneous coronary intervention and acute coronary syndromes. However, it has a relatively slow onset of action and a significant number of patients show variable degrees of responsiveness or "resistance" to it. Novel P2Y12 antagonists, including Cangrelor, Prasugrel and AZD6140, all currently in phase 3 trials, have a faster onset of action, as well as more potent and less variable inhibition of platelet function ex vivo [30]. PRT060128, an investigational, direct-acting, reversible P2Y12 antagonist with a novel structure (not disclosed) has completed phase 1 clinical studies [30].
Available Assays
DiscoveRx PathHunter® CHO-K1 P2RY12 β-Arrestin Cell Line (Cat no. 93-0262C2)
PathHunter® eXpress P2RY12 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0262E2CP0M)
more info

REFERENCES

1. Andre P, Delaney SM, LaRocca T, Vincent D, DeGuzman F, Jurek M, Koller B, Phillips DR, Conley PB. (2003) P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. J Clin Invest112: 398-406. [PMID:12897207]

2. Baqi Y, Atzler K, Köse M, Glänzel M, Müller CE. (2009) High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors. J. Med. Chem.52 (12): 3784-93. [PMID:19463000]

3. Barragan P, Bouvier JL, Roquebert PO, Macaluso G, Commeau P, Comet B, Lafont A, Camoin L, Walter U, Eigenthaler M. (2003) Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv59: 295-302. [PMID:12822144]

4. Bianco F, Fumagalli M, Pravettoni E, D'Ambrosi N, Volonté C, Matteoli M, Abbracchio MP, Verderio C. (2005) Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia. Brain Res Brain Res Rev48: 144-156. [PMID:15850653]

5. Bodor ET, Waldo GL, Hooks SB, Corbitt J, Boyer JL, Harden TK. (2003) Purification and functional reconstitution of the human P2Y12 receptor. Mol Pharmacol64: 1210-1216. [PMID:14573771]

6. Cattaneo M, Lecchi A, Randi AM, McGregor JL, Mannucci PM. (1992) Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate. Blood80 (11): 2787-96. [PMID:1333302]

7. Cattaneo M, Zighetti ML, Lombardi R, Martinez C, Lecchi A, Conley PB, Ware J, Ruggeri ZM. (2003) Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci U S A100: 1978-1983. [PMID:12578987]

8. Cavallari U, Trabetti E, Malerba G, Biscuola M, Girelli D, Olivieri O, Martinelli N, Angiolillo DJ, Corrocher R, Pignatti PF. (2007) Gene sequence variations of the platelet P2Y12 receptor are associated with coronary artery disease. BMC Med Genet8: 59-59. [PMID:17803810]

9. Ceruti S, Fumagalli M, Villa G, Verderio C, Abbracchio MP. (2008) Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium.43: 576-590. [PMID:18031810]

10. Chang H, Yanachkov IB, Dix EJ, Li YF, Barnard MR, Wright GE, Michelson AD, Frelinger 3rd AL. (2012) Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation. J. Thromb. Haemost.10 (12): 2573-80. [PMID:23083103]

11. Douglass JG, Patel RI, Yerxa BR, Shaver SR, Watson PS, Bednarski K, Plourde R, Redick CC, Brubaker K, Jones AC, Boyer JL. (2008) Lipophilic modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor. J Med Chem51: 1007-1025. [PMID:18232657]

12. El-Tayeb A, Griessmeier KJ, Müller CE. (2005) Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors. Bioorg. Med. Chem. Lett.15 (24): 5450-2. [PMID:16213725]

13. Evans DJ, Jackman LE, Chamberlain J, Crosdale DJ, Judge HM, Jetha K, Norman KE, Francis SE, Storey RF. (2009) Platelet P2Y(12) receptor influences the vessel wall response to arterial injury and thrombosis. Circulation119: 116-122. [PMID:19103996]

14. Fontana P, Dupont A, Gandrille S, Bachelot-Loza C, Reny JL, Aiach M, Gaussem P. (2003) Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation108: 989-995. [PMID:12912815]

15. Fontana P, Gaussem P, Aiach M, Fiessinger JN, Emmerich J, Reny JL. (2003) P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control study. Circulation108: 2971-2973. [PMID:14662702]

16. Gachet C. (2008) P2 receptors, platelet function and pharmacological implications. Thromb Haemost99: 466-472. [PMID:18327393]

17. Gretler DD, Conley PB, Andre P, Jurek M, Pandey A, Ronanko K, Leese PT, Hutchaleelaha A, Phillips DR. (2007) "First in human" experience with PRT060128, a new direct-acting, reversible, P2Y12 inhibitor for IV and oral use. J Am Coll Cardiol49: 326.

18. Hasegawa M, Sugidachi A, Ogawa T, Isobe T, Jakubowski JA, Asai F. (2005) Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thrombosis and haemostasis94 (3): 593-598. [PMID:16268477]

19. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WE, Julius D. (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nature Neuroscience19: 1512-1519. [PMID:17115040]

20. Herbert JM, Savi P. (2003) P2Y12, a new platelet ADP receptor, target of clopidogrel. Semin Vasc Med3: 113-122. [PMID:15199474]

21. Hoffmann K, Baqi Y, Morena MS, Glänzel M, Müller CE, von Kügelgen I. (2009) Interaction of new, very potent non-nucleotide antagonists with Arg256 of the human platelet P2Y12 receptor. J. Pharmacol. Exp. Ther.331 (2): 648-55. [PMID:19690189]

22. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB. (2001) Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature409: 202-207. [PMID:11196645]

23. Humphries RG, Tomlinson W, Clegg JA, Ingall AH, Kindon ND, Leff P. (1995) Pharmacological profile of the novel P2T-purinoceptor antagonist, FPL 67085 in vitro and in the anaesthetized rat in vivo. Br. J. Pharmacol.115 (6): 1110-6. [PMID:7582510]

24. Humphries RG, Tomlinson W, Ingall AH, Cage PA, Leff P. (1994) FPL 66096: a novel, highly potent and selective antagonist at human platelet P2T-purinoceptors. Br. J. Pharmacol.113 (3): 1057-63. [PMID:7858849]

25. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J. Med. Chem.45 (19): 4057-93. [PMID:12213051]

26. Kahner BN, Dorsam RT, Kunapuli SP. (2008) Role of P2Y receptor subtypes in platelet-derived microparticle generation. Front Biosci1: 433-439. [PMID:17981558]

27. Kennedy C, Chootip K, Mitchell C, Syed NI, Tengah A. (2013) P2X and P2Y nucleotide receptors as targets in cardiovascular disease. Future Med Chem5 (4): 431-49. [PMID:23495690]

28. Kobayashi K, Yamanaka H, Fukuoka T, Dai Y, Obata K, Noguchi K. (2008) P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain. J Neurosi28: 2892-2902. [PMID:18337420]

29. Masyuk AI, Gradilone SA, Banales JM, Huang BQ, Masyuk TV, Lee SO, Splinter PL, Stroope AJ, Larusso NF. (2008) Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am J Physiol Gastrointest Liver Physiol295: 725-734. [PMID:18687752]

30. Michelson AD. (2008) P2Y12 antagonism: promises and challenges. Arterioscler Thromb Vasc Biol28: s33-s38. [PMID:18174449]

31. Nonaka Y, Hiramoto T, Fujita N. (2005) Identification of endogenous surrogate ligands for human P2Y12 receptors by in silico and in vitro methods. Biochem Biophys Res Commun337: 281-288. [PMID:16185654]

32. Ohlmann P, Lecchi A, El-Tayeb A, Müller CE, Cattaneo M, Gachet C. (2013) The platelet P2Y(12) receptor under normal and pathological conditions. Assessment with the radiolabeled selective antagonist [(3)H]PSB-0413. Purinergic Signal.9 (1): 59-66. [PMID:22892887]

33. Ohsawa K, Irino Y, Nakamura Y, Akazawa C, Inoue K, Kohsaka S. (2007) Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia55: 604-616. [PMID:17299767]

34. Pausch MH, Lai M, Tseng E, Paulsen J, Bates B, Kwak S. (2004) Functional expression of human and mouse P2Y12 receptors in Saccharomyces cerevisiae. Biochem Biophys Res Commun324: 171-177. [PMID:15464998]

35. Post JM, Alexander S, Wang YX, Vincelette J, Vergona R, Kent L, Bryant J, Sullivan ME, Dole WP, Morser J, Subramanyam B. (2008) Novel P2Y12 adenosine diphosphate receptor antagonists for inhibition of platelet aggregation (II): pharmacodynamic and pharmacokinetic characterization. Thromb Res122: 533-540. [PMID:18539312]

36. Sasaki Y, Hoshi M, Akazawa C, Nakamura Y, Tsuzuki H, Inoue K, Kohsaka S. (2003) Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia44: 242-250. [PMID:14603465]

37. Schoenwaelder SM, Ono A, Sturgeon S, Chan SM, Mangin P, Maxwell MJ, Turnbull S, Mulchandani M, Anderson K, Kauffenstein G, Rewcastle GW, Kendall J, Gachet C, Salem HH, Jackson SP. (2007) Identification of unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets. J Biol Chem282: 28648-28658. [PMID:17673465]

38. Simon J, Filippov AK, Goransson S, Wong YH, Frelin C, Michel AD, Brown DA, Barnard EA. (2002) Characterization and channel coupling of the P2Y(12) nucleotide receptor of brain capillary endothelial cells. J Biol Chem277: 31390-31400. [PMID:12080041]

39. Srinivasan S, Mir F, Huang JS, Khasawneh F, Lam SC, Le Breton GC. (2009) The P2Y12 antagonists, 2MeSAMP and cangrelor (ARC69931MX) can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels. J Biol Chem, : -. [PMID:19346255]

40. Takasaki J, Kamohara M, Saito T, Matsumoto M, Matsumoto S, Ohishi T, Soga T, Matsushime H, Furuichi K. (2001) Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y(1) receptor. Mol Pharmacol60: 432-439. [PMID:11502873]

41. Tozaki-Saitoh H, Tsuda M, Ueda K, , and Inoue K. (2008) P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J Neurosi28: 4949-4956. [PMID:18463248]

42. Wihlborg AK, Wang L, Braun OO, Eyjolfsson A, Gustafsson R, Gudbjartsson T, Erlinge D. (2004) ADP receptor P2Y12 is expressed in vascular smooth muscle cells and stimulates contraction in human blood vessels. Arterioscler Thromb Vasc Biol24: 1810-1815. [PMID:15308557]

43. Zech G, Hessler G, Evers A, Weiss T, Florian P, Just M, Czech J, Czechtizky W, Görlitzer J, Ruf S et al.. (2012) Identification of high-affinity P2Y₁₂ antagonists based on a phenylpyrazole glutamic acid piperazine backbone. J. Med. Chem.55 (20): 8615-29. [PMID:22984835]

44. Zhang J, Zhang K, Gao Z-G, Paoletta S, Zhang D, Han GW, Li T, Ma, L, Zhang W, Müller CE et al.. (2014) Agonist-bound structure of the human P2Y12 receptor. Nature,  (509): 119-122.

45. Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L, Han GW, Moss SM, Paoletta S, Kiselev E, Lu W et al.. (2014) Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature,  [Epub ahead of print]. [PMID:24670650]

46. Ziegler S, Schillinger M, Funk M, Felber K, Exner M, Mlekusch W, Sabeti S, Amighi J, Minar E, Brunner M, Müller M, Mannhalter C. (2005) Association of a functional polymorphism in the clopidogrel target receptor gene, P2Y12, and the risk for ischemic cerebrovascular events in patients with peripheral artery disease. Stroke36: 1394-1399. [PMID:15933261]

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: P2Y12 receptor. Last modified on 10/06/2014. Accessed on 22/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=328.

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