P2Y12

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
Gene location (Human)
Chr.Chromosome 3 (human)[1]
BandNo data availableStart151,337,380 bp[1]
End151,384,812 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

64805

70839

Ensembl

ENSG00000169313

ENSMUSG00000036353

UniProt

Q9H244

Q9CPV9

RefSeq (mRNA)

NM_176876
NM_022788

NM_027571

RefSeq (protein)

NP_073625
NP_795345

NP_081847

Location (UCSC)Chr 3: 151.34 – 151.38 MbChr 3: 59.22 – 59.26 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] 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.[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). 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.[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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000169313 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036353 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  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. PMC 324551 Freely accessible. PMID 14755328. doi:10.1172/JCI20986.
  6. ↑ Murugappa S, Kunapuli SP (2006). "The role of ADP receptors in platelet function". Frontiers in Bioscience. 11 (1): 1977–86. PMID 16368572. doi:10.2741/1939.
  7. 1 2 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. PMID 11196645. doi:10.1038/35051599.
  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. PMC 4208629 Freely accessible. PMID 25954988. doi:10.1136/bmj.g6269.
  11. ↑ 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. PMID 16143698. doi:10.1001/jama.294.10.1224.

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.