In the field of purinergic signaling, the P2Y12protein on the periphery is found mainly but not exclusively on the surface of bloodplatelets, and is an important regulator in blood clotting.[9] In the central nervous system, this receptor has been found expressed exclusively on microglia, where it is necessary for physiological and pathological microglial actions, such as monitoring neuronal functions and microglial neuroprotection.[10]
The combination of a P2Y12 inhibitor and aspirin, called dual antiplatelet treatment, remains the first-line treatment for acute coronary syndrome. A 2019 randomized trial suggested that prasugrel is superior to ticagrelor.[11]
Antiplatelet treatment of STEMIedit
In patients undergoing primary percutaneous coronary intervention (PCI) for an ST-segment elevation myocardial infarction (STEMI), US,[12] European,[13] and Canadian[14] guidelines recommend that a P2Y12 inhibitor should be administered as soon as possible, although it is unclear whether administration of these medications before the patient arrives at the hospital confers additional benefits compared with in-hospital administration.[14]
On the other hand, P2Y12 inhibitors do not change the risk of death when given as a pretreatment prior to routine PCI in people who have had a non-ST-elevation myocardial infarction (NSTEMI). Though, a P2Y12 inhibitor in addition to aspirin should be administered for up to 12 months to most patients with non-ST-elevation acute coronary syndrome. They do however increase the risk of bleeding and decrease the risk of further cardiovascular problems. Thus their routine use in this context is of questionable value.[15]
A network meta-analysis of 37 studies involving 88,402 STEMI patients and 5,077 major adverse cardiac events (MACE) patients found that use of prasugrel was associated with lower mortality and MACE than other drugs in this class (clopidogrel and ticagrelor).[16]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000169313 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000036353 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abHollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, et al. (January 2001). "Identification of the platelet ADP receptor targeted by antithrombotic drugs". Nature. 409 (6817): 202–7. Bibcode:2001Natur.409..202H. doi:10.1038/35051599. PMID 11196645. S2CID 4423579.
^Nicholas RA (September 2001). "Identification of the P2Y(12) receptor: a novel member of the P2Y family of receptors activated by extracellular nucleotides". Molecular Pharmacology. 60 (3): 416–20. PMID 11502870.
^Murugappa S, Kunapuli SP (May 2006). "The role of ADP receptors in platelet function". Frontiers in Bioscience. 11 (1): 1977–86. doi:10.2741/1939. PMID 16368572.
^Dorsam RT, Kunapuli SP (February 2004). "Central role of the P2Y12 receptor in platelet activation". The Journal of Clinical Investigation. 113 (3): 340–5. doi:10.1172/JCI20986. PMC324551. PMID 14755328.
^Cserép C, Pósfai B, Lénárt N, Fekete R, László ZI, Lele Z, et al. (January 2020). "Microglia monitor and protect neuronal function through specialized somatic purinergic junctions". Science. 367 (6477): 528–537. Bibcode:2020Sci...367..528C. doi:10.1126/science.aax6752. PMID 31831638. S2CID 209343260.
^Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, et al. (October 2019). "Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes". The New England Journal of Medicine. 381 (16): 1524–1534. doi:10.1056/NEJMoa1908973. PMID 31475799.
^O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, et al. (American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines) (January 2013). "2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 127 (4): e362-425. doi:10.1161/CIR.0b013e3182742cf6. PMID 23247304.
^Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. (ESC Scientific Document Group) (January 2018). "2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)". European Heart Journal. 39 (2): 119–177. doi:10.1093/eurheartj/ehx393. PMID 28886621.
^ abWong GC, Welsford M, Ainsworth C, Abuzeid W, Fordyce CB, Greene J, et al. (members of the Secondary Panel) (February 2019). "2019 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Guidelines on the Acute Management of ST-Elevation Myocardial Infarction: Focused Update on Regionalization and Reperfusion". The Canadian Journal of Cardiology. 35 (2): 107–132. doi:10.1016/j.cjca.2018.11.031. PMID 30760415.
^Bellemain-Appaix A, Kerneis M, O'Connor SA, Silvain J, Cucherat M, Beygui F, et al. (October 2014). "Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis". BMJ. 349 (aug 06 2): g6269. doi:10.1136/bmj.g6269. PMC4208629. PMID 25954988.
^Rafique AM, Nayyar P, Wang TY, Mehran R, Baber U, Berger PB, et al. (May 2016). "Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta-Analysis". JACC. Cardiovascular Interventions. 9 (10): 1036–46. doi:10.1016/j.jcin.2016.02.013. PMID 27198684.
this, article, about, receptor, class, medications, adenosine, diphosphate, receptor, inhibitor, p2y12, chemoreceptor, adenosine, diphosphate, that, belongs, class, group, protein, coupled, gpcr, purinergic, receptors, this, receptor, family, several, receptor. This article is about the receptor For the class of medications see Adenosine diphosphate receptor inhibitor P2Y12 is a chemoreceptor for adenosine diphosphate ADP 5 6 that belongs to the Gi class of a group of G protein coupled GPCR purinergic receptors 7 This P2Y receptor family has several receptor subtypes with different pharmacological selectivity which overlaps in some cases for various adenosine and uridine nucleotides The P2Y12 receptor is involved in platelet aggregation and is thus a biological target for the treatment of thromboembolisms and other clotting disorders Two transcript variants encoding the same isoform have been identified for this gene 8 P2RY12Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4NTJ 4PXZ 4PY0IdentifiersAliasesP2RY12 ADPG R BDPLT8 HORK3 P2T AC P2Y 12 R P2Y AC P2Y ADP P2Y cyc P2Y12 SP1999 purinergic receptor P2Y12External IDsOMIM 600515 MGI 1918089 HomoloGene 11260 GeneCards P2RY12Gene location Human Chr Chromosome 3 human 1 Band3q25 1Start151 336 843 bp 1 End151 384 753 bp 1 Gene location Mouse Chr Chromosome 3 mouse 2 Band3 3 DStart59 123 693 bp 2 End59 170 292 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed ininferior ganglion of vagus nervesuperior vestibular nucleusventral tegmental areasubthalamic nucleusBrodmann area 46monocytecorpus callosumspinal gangliaspinal cordsubstantia nigraTop expressed inglobus pallidusbloodsuperior frontal gyrusmorulaoptic nerveolfactory tubercleRegion I of hippocampus properprimary motor cortexhippocampus propercarotid bodyMore reference expression dataBioGPSn aGene ontologyMolecular functionG protein coupled adenosine receptor activity G protein coupled receptor activity guanyl nucleotide exchange factor activity G protein coupled purinergic nucleotide receptor activity signal transducer activity G protein coupled ADP receptor activityCellular componentintegral component of membrane membrane plasma membrane integral component of plasma membrane cell surface basal plasma membrane mitochondrion caveola intrinsic component of membrane external side of plasma membraneBiological processhemostasis G protein coupled adenosine receptor signaling pathway regulation of calcium ion transport adenylate cyclase inhibiting G protein coupled receptor signaling pathway protein kinase B signaling adenylate cyclase modulating G protein coupled receptor signaling pathway negative regulation of cell differentiation substrate dependent cell migration cell extension cellular response to organic cyclic compound negative regulation of norepinephrine secretion G protein coupled purinergic nucleotide receptor signaling pathway regulation of microglial cell migration cell projection organization calcium ion transmembrane transport positive regulation of ion transport potassium ion transmembrane transport cellular response to ATP platelet aggregation glial cell migration signal transduction blood coagulation platelet activation G protein coupled receptor signaling pathway regulation of molecular functionSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez6480570839EnsemblENSG00000169313ENSMUSG00000036353UniProtQ9H244Q9CPV9RefSeq mRNA NM 176876NM 022788NM 027571NM 001357007NM 001357008NM 001357010RefSeq protein NP 073625NP 795345NP 081847NP 001343936NP 001343937NP 001343939Location UCSC Chr 3 151 34 151 38 MbChr 3 59 12 59 17 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseIn the field of purinergic signaling the P2Y12 protein on the periphery is found mainly but not exclusively on the surface of blood platelets and is an important regulator in blood clotting 9 In the central nervous system this receptor has been found expressed exclusively on microglia where it is necessary for physiological and pathological microglial actions such as monitoring neuronal functions and microglial neuroprotection 10 Contents 1 P2Y12 antagonists 1 1 For acute coronary syndrome 1 2 Antiplatelet treatment of STEMI 2 References 3 External linksP2Y12 antagonists editThe drugs clopidogrel Plavix prasugrel Efient Effient ticagrelor Brilinta and cangrelor Kengreal bind to this receptor and are marketed as antiplatelet agents 5 For acute coronary syndrome edit The combination of a P2Y12 inhibitor and aspirin called dual antiplatelet treatment remains the first line treatment for acute coronary syndrome A 2019 randomized trial suggested that prasugrel is superior to ticagrelor 11 Antiplatelet treatment of STEMI edit In patients undergoing primary percutaneous coronary intervention PCI for an ST segment elevation myocardial infarction STEMI US 12 European 13 and Canadian 14 guidelines recommend that a P2Y12 inhibitor should be administered as soon as possible although it is unclear whether administration of these medications before the patient arrives at the hospital confers additional benefits compared with in hospital administration 14 On the other hand P2Y12 inhibitors do not change the risk of death when given as a pretreatment prior to routine PCI in people who have had a non ST elevation myocardial infarction NSTEMI Though a P2Y12 inhibitor in addition to aspirin should be administered for up to 12 months to most patients with non ST elevation acute coronary syndrome They do however increase the risk of bleeding and decrease the risk of further cardiovascular problems Thus their routine use in this context is of questionable value 15 A network meta analysis of 37 studies involving 88 402 STEMI patients and 5 077 major adverse cardiac events MACE patients found that use of prasugrel was associated with lower mortality and MACE than other drugs in this class clopidogrel and ticagrelor 16 References edit a b c GRCh38 Ensembl release 89 ENSG00000169313 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000036353 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Hollopeter G Jantzen HM Vincent D Li G England L Ramakrishnan V et al January 2001 Identification of the platelet ADP receptor targeted by antithrombotic drugs Nature 409 6817 202 7 Bibcode 2001Natur 409 202H doi 10 1038 35051599 PMID 11196645 S2CID 4423579 Nicholas RA September 2001 Identification of the P2Y 12 receptor a novel member of the P2Y family of receptors activated by extracellular nucleotides Molecular Pharmacology 60 3 416 20 PMID 11502870 Murugappa S Kunapuli SP May 2006 The role of ADP receptors in platelet function Frontiers in Bioscience 11 1 1977 86 doi 10 2741 1939 PMID 16368572 Entrez Gene P2RY12 purinergic receptor P2Y G protein coupled 12 Dorsam RT Kunapuli SP February 2004 Central role of the P2Y12 receptor in platelet activation The Journal of Clinical Investigation 113 3 340 5 doi 10 1172 JCI20986 PMC 324551 PMID 14755328 Cserep C Posfai B Lenart N Fekete R Laszlo ZI Lele Z et al January 2020 Microglia monitor and protect neuronal function through specialized somatic purinergic junctions Science 367 6477 528 537 Bibcode 2020Sci 367 528C doi 10 1126 science aax6752 PMID 31831638 S2CID 209343260 Schupke S Neumann FJ Menichelli M Mayer K Bernlochner I Wohrle J et al October 2019 Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes The New England Journal of Medicine 381 16 1524 1534 doi 10 1056 NEJMoa1908973 PMID 31475799 O Gara PT Kushner FG Ascheim DD Casey DE Chung MK de Lemos JA et al American College of Cardiology Foundation American Heart Association Task Force on Practice Guidelines January 2013 2013 ACCF AHA guideline for the management of ST elevation myocardial infarction a report of the American College of Cardiology Foundation American Heart Association Task Force on Practice Guidelines Circulation 127 4 e362 425 doi 10 1161 CIR 0b013e3182742cf6 PMID 23247304 Ibanez B James S Agewall S Antunes MJ Bucciarelli Ducci C Bueno H et al ESC Scientific Document Group January 2018 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST segment elevation of the European Society of Cardiology ESC European Heart Journal 39 2 119 177 doi 10 1093 eurheartj ehx393 PMID 28886621 a b Wong GC Welsford M Ainsworth C Abuzeid W Fordyce CB Greene J et al members of the Secondary Panel February 2019 2019 Canadian Cardiovascular Society Canadian Association of Interventional Cardiology Guidelines on the Acute Management of ST Elevation Myocardial Infarction Focused Update on Regionalization and Reperfusion The Canadian Journal of Cardiology 35 2 107 132 doi 10 1016 j cjca 2018 11 031 PMID 30760415 Bellemain Appaix A Kerneis M O Connor SA Silvain J Cucherat M Beygui F et al October 2014 Reappraisal of thienopyridine pretreatment in patients with non ST elevation acute coronary syndrome a systematic review and meta analysis BMJ 349 aug 06 2 g6269 doi 10 1136 bmj g6269 PMC 4208629 PMID 25954988 Rafique AM Nayyar P Wang TY Mehran R Baber U Berger PB et al May 2016 Optimal P2Y12 Inhibitor in Patients With ST Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention A Network Meta Analysis JACC Cardiovascular Interventions 9 10 1036 46 doi 10 1016 j jcin 2016 02 013 PMID 27198684 External links editThis article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title P2Y12 amp oldid 1189253117, wikipedia, wiki, book, books, library,
