P2Y receptor

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.

Coupling

The biological effects of P2Y receptor activation depends on how they couple to downstream signalling pathways, either via G_i, G_q/11 or G_s 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	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.

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

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. ^ 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. 
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. doi:10.1093/eurheartj/ehl410. PMID 17135283. 
5. ^ 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. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1294. 
• MeSH Purinergic+P2+receptors