P2Y12: Difference between revisions
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{{Short description|Protein-coding gene in the species Homo sapiens}} |
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{{DISPLAYTITLE:P2Y<sub>12</sub>}} |
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{{About|the receptor|the class of medications|Adenosine diphosphate receptor inhibitor}} |
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{{Infobox_gene}} |
{{Infobox_gene}} |
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'''P2Y<sub>12</sub>''' is a [[chemoreceptor]] for [[adenosine diphosphate]] (ADP)<ref name="pmid11196645">{{cite journal | vauthors = Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB | title = Identification of the platelet ADP receptor targeted by antithrombotic drugs | journal = Nature | volume = 409 | issue = 6817 | pages = 202–7 | date = |
'''P2Y<sub>12</sub>''' is a [[chemoreceptor]] for [[adenosine diphosphate]] (ADP)<ref name="pmid11196645">{{cite journal | vauthors = Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB | s2cid = 4423579 | display-authors = 6 | title = Identification of the platelet ADP receptor targeted by antithrombotic drugs | journal = Nature | volume = 409 | issue = 6817 | pages = 202–7 | date = January 2001 | pmid = 11196645 | doi = 10.1038/35051599 | bibcode = 2001Natur.409..202H }}</ref><ref name="pmid11502870">{{cite journal | vauthors = Nicholas RA | title = Identification of the P2Y(12) receptor: a novel member of the P2Y family of receptors activated by extracellular nucleotides | journal = Molecular Pharmacology | volume = 60 | issue = 3 | pages = 416–20 | date = September 2001 | pmid = 11502870 | url = http://molpharm.aspetjournals.org/cgi/content/full/60/3/416 }}</ref> that belongs to the [[Gi alpha subunit|G<sub>i</sub>]] class of a group of [[G protein-coupled receptor|G protein-coupled]] (GPCR) [[purinergic receptors]].<ref name="pmid16368572">{{cite journal | vauthors = Murugappa S, Kunapuli SP | title = The role of ADP receptors in platelet function | journal = Frontiers in Bioscience | volume = 11 | issue = 1 | pages = 1977–86 | date = May 2006 | pmid = 16368572 | doi = 10.2741/1939 | doi-access = free }}</ref> This [[P2Y receptor]] family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various [[adenosine]] and [[uridine]] [[nucleotide]]s. The P2Y<sub>12</sub> receptor is involved in [[platelet aggregation#Adhesion and aggregation|platelet aggregation]] and is thus a [[biological target]] for the treatment of [[thrombosis|thromboembolism]]s and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: P2RY12 purinergic receptor P2Y, G-protein coupled, 12| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64805}}</ref> |
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In the field of [[purinergic signaling]], the '''P2Y<sub>12</sub>''' [[protein]] on the periphery is found mainly but not exclusively on the surface of [[blood]] [[platelet]]s, and is an important regulator in blood [[coagulation|clotting]].<ref name="pmid14755328">{{cite journal | vauthors = Dorsam RT, Kunapuli SP | title = Central role of the P2Y12 receptor in platelet activation | journal = The Journal of Clinical Investigation | volume = 113 | issue = 3 | pages = 340–5 | date = |
In the field of [[purinergic signaling]], the '''P2Y<sub>12</sub>''' [[protein]] on the periphery is found mainly but not exclusively on the surface of [[blood]] [[platelet]]s, and is an important regulator in blood [[coagulation|clotting]].<ref name="pmid14755328">{{cite journal | vauthors = Dorsam RT, Kunapuli SP | title = Central role of the P2Y12 receptor in platelet activation | journal = The Journal of Clinical Investigation | volume = 113 | issue = 3 | pages = 340–5 | date = February 2004 | pmid = 14755328 | pmc = 324551 | doi = 10.1172/JCI20986 }}</ref> 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.<ref>{{cite journal | vauthors = Cserép C, Pósfai B, Lénárt N, Fekete R, László ZI, Lele Z, Orsolits B, Molnár G, Heindl S, Schwarcz AD, Ujvári K, Környei Z, Tóth K, Szabadits E, Sperlágh B, Baranyi M, Csiba L, Hortobágyi T, Maglóczky Z, Martinecz B, Szabó G, Erdélyi F, Szipőcs R, Tamkun MM, Gesierich B, Duering M, Katona I, Liesz A, Tamás G, Dénes Á | s2cid = 209343260 | display-authors = 6 | title = Microglia monitor and protect neuronal function through specialized somatic purinergic junctions | journal = Science | volume = 367 | issue = 6477 | pages = 528–537 | date = January 2020 | pmid = 31831638 | doi = 10.1126/science.aax6752 | bibcode = 2020Sci...367..528C | url = https://epub.ub.uni-muenchen.de/76442/ }}</ref> |
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== |
== P2Y<sub>12</sub> antagonists == |
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The drugs [[clopidogrel]] (Plavix), [[prasugrel]] (Efient, Effient), [[ticagrelor]] (Brilinta), and [[cangrelor]] (Kengreal) bind to this receptor and are marketed as [[antiplatelet]] agents.<ref name="pmid11196645" /> |
The drugs [[clopidogrel]] (Plavix), [[prasugrel]] (Efient, Effient), [[ticagrelor]] (Brilinta), and [[cangrelor]] (Kengreal) bind to this receptor and are marketed as [[antiplatelet]] agents.<ref name="pmid11196645" /> |
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=== For acute coronary syndrome === |
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The combination of |
The combination of a P2Y<sub>12</sub> 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.<ref>{{cite journal | vauthors = Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, Richardt G, Liebetrau C, Witzenbichler B, Antoniucci D, Akin I, Bott-Flügel L, Fischer M, Landmesser U, Katus HA, Sibbing D, Seyfarth M, Janisch M, Boncompagni D, Hilz R, Rottbauer W, Okrojek R, Möllmann H, Hochholzer W, Migliorini A, Cassese S, Mollo P, Xhepa E, Kufner S, Strehle A, Leggewie S, Allali A, Ndrepepa G, Schühlen H, Angiolillo DJ, Hamm CW, Hapfelmeier A, Tölg R, Trenk D, Schunkert H, Laugwitz KL, Kastrati A | display-authors = 6 | title = Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes | journal = The New England Journal of Medicine | volume = 381 | issue = 16 | pages = 1524–1534 | date = October 2019 | pmid = 31475799 | doi = 10.1056/NEJMoa1908973 | doi-access =free }}</ref> |
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=== Antiplatelet treatment of STEMI === |
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In patients undergoing primary PCI for an ST-segment elevation myocardial infarction (STEMI), US,<ref name="AHAACCguideline">{{cite journal |vauthors=O'Gara PT, Kushner FG, Ascheim DD, Casey DE |
In patients undergoing primary [[percutaneous coronary intervention]] (PCI) for an ST-segment elevation myocardial infarction (STEMI), US,<ref name="AHAACCguideline">{{cite journal | vauthors = O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW | display-authors = 6 | title = 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 | journal = Circulation | volume = 127 | issue = 4 | pages = e362-425 | date = January 2013 | pmid = 23247304 | doi = 10.1161/CIR.0b013e3182742cf6 | collaboration = American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines | doi-access = free }}</ref> European,<ref name="ESCguideline">{{cite journal | vauthors = Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio AL, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P | display-authors = 6 | title = 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) | journal = European Heart Journal | volume = 39 | issue = 2 | pages = 119–177 | date = January 2018 | pmid = 28886621 | doi = 10.1093/eurheartj/ehx393 | collaboration = ESC Scientific Document Group | doi-access = free }}</ref> and Canadian<ref name="CCSguideline">{{cite journal | vauthors = Wong GC, Welsford M, Ainsworth C, Abuzeid W, Fordyce CB, Greene J, Huynh T, Lambert L, Le May M, Lutchmedial S, Mehta SR, Natarajan M, Norris CM, Overgaard CB, Perry Arnesen M, Quraishi A, Tanguay JF, Traboulsi M, van Diepen S, Welsh R, Wood DA, Cantor WJ | display-authors = 6 | title = 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 | journal = The Canadian Journal of Cardiology | volume = 35 | issue = 2 | pages = 107–132 | date = February 2019 | pmid = 30760415 | doi = 10.1016/j.cjca.2018.11.031 | collaboration = members of the Secondary Panel | doi-access = free }}</ref> guidelines recommend that a P2Y<sub>12</sub> 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.<ref name="CCSguideline"/> |
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On the other hand, P2Y<sub>12</sub> inhibitors do not change the risk of death when given as a pretreatment prior to routine |
On the other hand, P2Y<sub>12</sub> 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 P2Y<sub>12</sub> 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.<ref name=BMJP2Y12>{{cite journal | vauthors = Bellemain-Appaix A, Kerneis M, O'Connor SA, Silvain J, Cucherat M, Beygui F, Barthélémy O, Collet JP, Jacq L, Bernasconi F, Montalescot G | display-authors = 6 | title = Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis | journal = BMJ | volume = 349 | issue = aug 06 2 | pages = g6269 | date = October 2014 | pmid = 25954988 | pmc = 4208629 | doi = 10.1136/bmj.g6269 | doi-access = free }}</ref> |
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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).<ref name="Rafique2016">{{cite journal |vauthors=Rafique AM, Nayyar P, Wang TY, Mehran R, Baber U, Berger PB, Tobis J, Currier J, Dave RH, Henry TD |title=Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta-Analysis |journal=JACC |
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).<ref name="Rafique2016">{{cite journal | vauthors = Rafique AM, Nayyar P, Wang TY, Mehran R, Baber U, Berger PB, Tobis J, Currier J, Dave RH, Henry TD | display-authors = 6 | title = Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta-Analysis | journal = JACC. Cardiovascular Interventions | volume = 9 | issue = 10 | pages = 1036–46 | date = May 2016 | pmid = 27198684 | doi = 10.1016/j.jcin.2016.02.013 | doi-access = free }}</ref> |
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== References == |
== References == |
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== External links == |
== External links == |
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* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2402 | title = P2Y Receptors: P2Y<sub>12</sub> | accessdate = | author = | authorlink = | vauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }} |
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* {{MeshName|purinoceptor+P2Y12}} |
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* {{PDBe-KB2|Q9H244|Human P2Y purinoceptor 12}} |
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Latest revision as of 18:32, 10 December 2023
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]
In 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]
P2Y12 antagonists
[edit]The 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.
- ^ 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.
- ^ 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
[edit]This article incorporates text from the United States National Library of Medicine, which is in the public domain.