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P2Y receptor

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Title: P2Y receptor  
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Subject: Lysophosphatidic acid receptor, P2Y12, Adenosine receptor, Purinergic receptor, Bombesin receptor
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P2Y receptor

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.

Contents

  • Coupling 1
  • Clinical significance 2
  • References 3
  • External links 4

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

  • 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]

References

  1. ^ 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.  
  2. ^ 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
  3. ^ 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.  
  4. ^ 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.  
  5. ^ Herbert JM, Savi P (2003). "P2Y12, a new platelet ADP receptor, target of clopidogrel". Seminars in vascular medicine 3 (2): 113–22.  

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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