P2Y12: Difference between revisions

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In the field of [[purinergic signaling]], the '''P2Y<sub>12</sub>''' [[protein]] 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 = Feb 2004 | pmid = 14755328 | pmc = 324551 | doi = 10.1172/JCI20986 | url = http://www.jci.org/articles/view/20986/files/pdf }}</ref>
{{CMG}}


==OVerview==
P2Y<sub>12</sub> belongs to the Gi 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 | year = 2006 | pmid = 16368572 | doi = 10.2741/1939 }}</ref> and 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 = Jan 2001 | pmid = 11196645 | doi = 10.1038/35051599 }}</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 = Sep 2001 | pmid = 11502870 | doi =  | url = http://molpharm.aspetjournals.org/cgi/content/full/60/3/416 }}</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 P2Y12 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| accessdate = }}</ref>


In the field of [[molecular biology]], the '''P2Y<sub>12</sub>''' [[protein]] 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 | author = Dorsam RT, Kunapuli SP | title = Central role of the P2Y12 receptor in platelet activation | journal = J. Clin. Invest. | volume = 113 | issue = 3 | pages = 340–5 | year = 2004 | pmid = 14755328 | doi = 10.1172/JCI200420986 | pmc = 324551 }}</ref>
== Clinical significance ==


P2Y<sub>12</sub> belongs to the Gi class of a group of [[G protein-coupled receptor|G protein-coupled]] (GPCR) [[purinergic receptors]]<ref name="pmid16368572">{{cite journal | author = Murugappa S, Kunapuli SP | title = The role of ADP receptors in platelet function | journal = Front. Biosci. | volume = 11 | issue = 1| pages = 1977–86 | year = 2006 | pmid = 16368572 | doi = 10.2741/1939 }}</ref> and is a [[chemoreceptor]] for [[adenosine diphosphate]] (ADP).<ref name="pmid11196645">{{cite journal | author = 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 | year = 2001 | pmid = 11196645 | doi = 10.1038/35051599 }}</ref><ref name="pmid11502870">{{cite journal | author = Nicholas RA | title = Identification of the P2Y(12) receptor: a novel member of the P2Y family of receptors activated by extracellular nucleotides | journal = Mol. Pharmacol. | volume = 60 | issue = 3 | pages = 416–20 | year = 2001 | pmid = 11502870 | doi = | issn = | url = http://molpharm.aspetjournals.org/cgi/content/full/60/3/416}}</ref> The P2Y family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various [[adenosine]] and [[uridine]] [[nucleotide]]s. This receptor is involved in [[platelet_aggregation#Adhesion_and_aggregation|platelet aggregation]], and is a potential 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 = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64805| accessdate = }}</ref>
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" />


==Clinical significance==
P2Y<sub>12</sub> inhibitors do not change the risk of death when given as a pretreatment prior to routine [[percutaneous coronary intervention]] (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.<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 | 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 | year = 2014 | pmid = 25954988 | doi = 10.1136/bmj.g6269 | pmc=4208629}}</ref>


The drugs [[clopidogrel]] (PLAVIX), [[prasugrel]] (Efient, Effient), [[ticagrelor]] (BRILINTA), and [[cangrelor]] bind to this receptor and are marketed as [[antiplatelet]] agents.<ref name="pmid11196645" />
In patients undergoing primary PCI for an ST-segment elevation myocardial infarction (STEMI), a P2Y<sub>12</sub> inhibitor should be administered as soon as possible. The use of clopidogrel in particular has been shown to improve morbidity and mortality endpoints including cardiovascular death, recurrent MI, and stroke at 30 days after PCI.<ref name =JAMAP2Y12>{{cite journal | vauthors = Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E |others = Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators | title = Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study | journal = JAMA | volume = 294 | issue = 10 | pages = 1224–32 | date = Sep 2005 | pmid = 16143698 | doi = 10.1001/jama.294.10.1224 }}</ref>
 
==References==


== References ==
{{Reflist|2}}
{{Reflist|2}}


==External links==
== External links ==
 
* {{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 = }}
*{{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2402 | title = P2Y Receptors: P2Y<sub>12</sub> | accessdate = | author = | authorlink = | coauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
* {{MeshName|purinoceptor+P2Y12}}
* {{MeshName|purinoceptor+P2Y12}}


{{NLM content}}
{{NLM content}}
{{G protein-coupled receptors}}
{{G protein-coupled receptors}}
[[Category:G protein coupled receptors]]
{{Purinergics}}


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Latest revision as of 14:02, 4 November 2018

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In the field of purinergic signaling, the P2Y12 protein is found mainly but not exclusively on the surface of blood platelets, and is an important regulator in blood clotting.[1]

P2Y12 belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors[2] and is a chemoreceptor for adenosine diphosphate (ADP).[3][4] 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.[5]

Clinical significance

The drugs clopidogrel (Plavix), prasugrel (Efient, Effient), ticagrelor (Brilinta), and cangrelor (Kengreal) bind to this receptor and are marketed as antiplatelet agents.[3]

P2Y12 inhibitors do not change the risk of death when given as a pretreatment prior to routine percutaneous coronary intervention (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.[6]

In patients undergoing primary PCI for an ST-segment elevation myocardial infarction (STEMI), a P2Y12 inhibitor should be administered as soon as possible. The use of clopidogrel in particular has been shown to improve morbidity and mortality endpoints including cardiovascular death, recurrent MI, and stroke at 30 days after PCI.[7]

References

  1. ↑ Dorsam RT, Kunapuli SP (Feb 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.
  2. ↑ Murugappa S, Kunapuli SP (2006). "The role of ADP receptors in platelet function". Frontiers in Bioscience. 11 (1): 1977–86. doi:10.2741/1939. PMID 16368572.
  3. ↑ 3.0 3.1 Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB (Jan 2001). "Identification of the platelet ADP receptor targeted by antithrombotic drugs". Nature. 409 (6817): 202–7. doi:10.1038/35051599. PMID 11196645.
  4. ↑ Nicholas RA (Sep 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.
  5. ↑ "Entrez Gene: P2RY12 purinergic receptor P2Y, G-protein coupled, 12".
  6. ↑ Bellemain-Appaix A, Kerneis M, O'Connor SA, Silvain J, Cucherat M, Beygui F, Barthélémy O, Collet JP, Jacq L, Bernasconi F, Montalescot G (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.
  7. ↑ Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E (Sep 2005). Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. "Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study". JAMA. 294 (10): 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698.

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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