P2Y12
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] 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.[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). 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
- ↑ 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.
- ↑ 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.
- 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. doi:10.1038/35051599. PMID 11196645.
- ↑ 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.
- ↑ "Entrez Gene: P2RY12 purinergic receptor P2Y, G-protein coupled, 12".
- ↑ 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. PMID 25954988.
- ↑ Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E, Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators (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): 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698.
External links
- "P2Y Receptors: P2Y12". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- purinoceptor P2Y12 at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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