P2Y receptor

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P2Y receptors are a family of purinergic receptors, 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

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:

Type Coupling Nucleotide
P2RY1 Gq/11 ADP
P2RY2 Gq/11 ATP, UTP
P2RY4 Gi and Gq/11 UTP
P2RY5 Lysophosphatidic acid[2]
P2RY6 Gq/11 UDP
P2RY8 orphan receptor
P2RY9 or GPR23 Lysophosphatidic acid
P2RY10 orphan receptor
P2RY11 Gs and Gq/11 ATP
P2RY12 Gi ADP
P2RY13 Gi ADP
P2RY14 Gq/11 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.

P2Y3 is the avian homologue of the mammalian P2Y6.[3]

Clinical significance

  • P2Y11 is a regulator of immune response, and a common polymorphism caried 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.[5]

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. doi:10.1124/pr.58.3.3. PMID 16968944. 
  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. ^ Li Q, Olesky M, Palmer RK, Harden TK, Nicholas RA. Evidence that the P2Y3 receptor is the avian homologue of the mammalian P2Y6 receptor. Mol Pharmacol. 1998 Sep;54(3):541-6. PMID: 9730913 [PubMed - indexed for MEDLINE]
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 

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v • d • e
Transmembrane receptor: G protein-coupled receptors
Class A: Rhodopsin like
Acetylcholine (M1, M2, M3, M4, M5) - Adrenergic (α1 (A, B, D), α2 (A, B, C), β1, β2, β3) - Adrenomedullin - Anaphylatoxin (C3a, C5a) - Angiotensin (1, 2) - Apelin - Bile acid - Bombesin (BRS3, GRPR, NMBR) - Bradykinin (B1, B2) - Cannabinoid (CB1, CB2) - Chemokine - Cholecystokinin (A, B) - Dopamine (D1, D2, D3, D4, D5) - Eicosanoid (CysLT (1, 2), LTB4 (1, 2), FPRL1, OXE, Prostaglandin ((DP (1, 2), EP (1, 2, 3, 4), PGF, Prostacyclin, Thromboxane) - EBI2 - Endothelin (A, B) - Estrogen - Formyl peptide (1, L1, L2) - Free fatty acid (1, 2, 3, 4) - FSH - Galanin (1, 2, 3) - Gonadotropin-releasing hormone (1, 2) - GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182) - Ghrelin - Histamine (H1, H2, H3, H4) - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) - MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) - Melanocortin (1, 2, 3, 4, 5) - MCHR (1, 2) - Melatonin (1A, 1B)- Motilin - neuromedin (B, U (1, 2)) - Neuropeptide (B/W (1, 2), FF (1, 2), S, Y (1, 2, 4, 5)) - Neurotensin (1, 2) - Opioid (Delta, Kappa, Mu, Nociceptin, but not Sigma) - Olfactory - Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) - Orexin (1, 2) - Oxytocin - Oxoglutarate - PAF - Prokineticin (1, 2) - Prolactin-releasing peptide - Protease-activated (1, 2, 3, 4) - Purinergics (Adenosine (A1, A2a, A2b, A3), P2Y, (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)) - Relaxin (1, 2, 3, 4) - Somatostatin (1, 2, 3, 4, 5) - Serotonin, all but 5-HT3 (5-HT1 (A, B, D, E, F), 5-HT2 (A, B, C), 5-HT (4, 5A, 6, 7)) - SREB - Succinate - TAAR (1, 2, 3, 5, 6, 8, 9) - Tachykinin (1, 2, 3) - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin (1A, 1B, 2)
Class B: Secretin like
Class C: Metabotropic
glutamate / pheromone
Calcium-sensing receptor - GABA B (1, 2) - Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) - GPRC6A - GPR (156, 158, 179) - RAIG (1, 2, 3, 4) - Taste receptors (TAS1R (1, 2, 3) TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50))
Frizzled / Smoothened
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - Smoothened

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