Jump to content

P2Y12: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m Journal cites:, added 1 PMC using AWB (12061)
Line 1: Line 1:
{{Infobox_gene}}
{{Infobox_gene}}
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/JCI200420986 }}</ref>
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/JCI200420986 }}</ref>


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> 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>
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> 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>


== Clinical significance ==
== Clinical significance ==
Line 8: Line 8:
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" />


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]]). 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 }}</ref>
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]]). 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>


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>
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 ==

Revision as of 17:56, 31 July 2016

P2RY12
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesP2RY12, ADPG-R, BDPLT8, HORK3, P2T(AC), P2Y(12)R, P2Y(AC), P2Y(ADP), P2Y(cyc), P2Y12, SP1999, purinergic receptor P2Y12
External IDsOMIM: 600515; MGI: 1918089; HomoloGene: 11260; GeneCards: P2RY12; OMA:P2RY12 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

64805

70839

Ensembl

ENSG00000169313

ENSMUSG00000036353

UniProt

Q9H244

Q9CPV9

RefSeq (mRNA)

NM_176876
NM_022788

NM_027571
NM_001357007
NM_001357008
NM_001357010

RefSeq (protein)

NP_073625
NP_795345

NP_081847
NP_001343936
NP_001343937
NP_001343939

Location (UCSC)Chr 3: 151.34 – 151.38 MbChr 3: 59.12 – 59.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

P2Y12 belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors[6] and is a chemoreceptor for adenosine diphosphate (ADP).[7][8] The P2Y family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.[9]

Clinical significance

The drugs, clopidogrel (Plavix), prasugrel (Efient, Effient), ticagrelor (Brilinta), and cangrelor (Kengreal) bind to this receptor and are marketed as antiplatelet agents.[7]

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). 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.[10]

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.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000169313 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036353 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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/JCI200420986. PMC 324551. PMID 14755328.
  6. ^ 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.
  7. ^ a b 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.
  8. ^ 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.
  9. ^ "Entrez Gene: P2RY12 purinergic receptor P2Y, G-protein coupled, 12".
  10. ^ 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.
  11. ^ Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E (Sep 2005). "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). Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators: 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698.

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

Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=P2Y12&oldid=732393259"