P2Y receptor
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P2Y receptors are a family of purinergic G protein-coupled receptors, stimulated by nucleotides such as ATP, ADP, UTP, UDP and UDP-glucose. To date, 12 P2Y receptors have been cloned in humans: P2Y1, P2Y2, P2Y4, P2Y5, P2Y6, P2Y8, P2Y9 (present in NCBI as GPR23), P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14.[1]
P2Y receptors are present in almost all human tissues where they exert various biological functions based on their G-protein coupling.
Coupling
The biological effects of P2Y receptor activation depends on how they couple to downstream signalling pathways, either via Gi, Gq/11 or Gs G proteins. Human P2Y receptors have the following G protein coupling:
| Protein | Gene | Coupling | Nucleotide |
| P2RY1 | P2RY1 | Gq/11 | ADP |
| P2RY2 | P2RY2 | Gq/11 | ATP, UTP |
| P2RY4 | P2RY4 | Gi and Gq/11 | UTP |
| P2RY5 / LPA6 | LPAR6 | Lysophosphatidic acid[2] | |
| P2RY6 | P2RY6 | Gq/11 | UDP |
| P2RY8 | P2RY8 | orphan receptor | |
| P2RY9 / LPAR4 / GPR23 | LPAR4 | Lysophosphatidic acid | |
| P2RY10 | P2RY10 | orphan receptor | |
| P2RY11 | P2RY11 | Gs and Gq/11 | ATP |
| P2RY12 | P2RY12 | Gi | ADP |
| P2RY13 | P2RY13 | Gi | ADP |
| P2RY14 | P2RY14 | Gi | UDP-glucose |
The gaps in P2Y receptor numbering is due to that several receptors (P2Y3, P2Y5, P2Y7, P2Y8, P2Y9, P2Y10) were thought to be P2Y receptors when they were cloned, when in fact they are not.
Clinical significance
- P2Y2 is a potential drug target for treating cystic fibrosis.[3]
- P2Y11 is a regulator of immune response, and a common polymorphism carried by almost 20% of North European caucasians give increased risk of myocardial infarction, making P2Y11 an interesting drug target candidate for treatment of myocardial infarction.[4]
- P2Y12 is the target of the anti-platelet drug clopidogrel[5] and other thienopyridines.
References
- ↑ Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA (2006). "International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy". Pharmacol. Rev. 58 (3): 281–341. doi:10.1124/pr.58.3.3. PMC 3471216. PMID 16968944.
- ↑ Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC. "G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth." Nature Genetics 2008 Mar;40(3):329-34. PMID 18297070
- ↑ Kellerman D, Evans R, Mathews D, Shaffer C (2002). "Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease". Adv. Drug Deliv. Rev. 54 (11): 1463–74. doi:10.1016/S0169-409X(02)00154-0. PMID 12458155.
- ↑ Amisten S, Melander O, Wihlborg AK, Berglund G, Erlinge D (2007). "Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y11". Eur. Heart J. 28 (1): 13–8. doi:10.1093/eurheartj/ehl410. PMID 17135283.
- ↑ Herbert JM, Savi P (2003). "P2Y12, a new platelet ADP receptor, target of clopidogrel". Seminars in vascular medicine 3 (2): 113–22. doi:10.1055/s-2003-40669. PMID 15199474.
External links
- Ivar von Kügelgen: Pharmacology of mammalian P2X- and P2Y-receptors, BIOTREND Reviews No. 03, September 2008,© 2008 BIOTREND Chemicals AG
- "P2Y Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Purinergic P2 receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
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