View source for P2Y receptor

'''P2Y receptors''' are a family of [[purinergic receptor]]s, [[G protein-coupled receptor]]s stimulated by [[nucleotide]]s such as [[Adenosine triphosphate|ATP]], [[Adenosine diphosphate|ADP]], [[Uridine triphosphate|UTP]], [[Uridine diphosphate|UDP]] and [[UDP-glucose]]. To date, 12 P2Y receptors have been cloned in humans: [[P2RY1| P2Y<sub>1</sub>]], [[P2RY2|P2Y<sub>2</sub>]], [[P2RY4|P2Y<sub>4</sub>]], [[P2RY5|P2Y<sub>5</sub>]], [[P2RY6|P2Y<sub>6</sub>]], [[P2RY8|P2Y<sub>8</sub>]], [[GPR23|P2Y<sub>9</sub>]] (present in NCBI as GPR23), [[P2RY10| P2Y<sub>10</sub>]], [[P2RY11|P2Y<sub>11</sub>]], [[P2RY12| P2Y<sub>12</sub>]], [[P2RY13|P2Y<sub>13</sub>]] and [[P2RY14|P2Y<sub>14</sub>]].<ref name="pmid16968944">{{cite journal | author = Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA | title = International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy | journal = Pharmacol. Rev. | volume = 58 | issue = 3 | pages = 281–341 | year = 2006 | pmid = 16968944 | doi = 10.1124/pr.58.3.3 }}</ref>

P2Y receptors are present in almost all [[human tissue]]s 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 alpha subunit|G<sub>i</sub>]], [[Gq protein|G<sub>q/11</sub>]] or [[G(s)alpha|G<sub>s</sub>]] G proteins. Human P2Y receptors have the following G protein coupling:

{| class="wikitable"
| width="160pt" | '''Protein''' || width="100pt" | '''Gene''' || width="100pt" | '''Coupling''' || '''[[Nucleotide]]'''
 |- 
 | [[P2RY1|P2RY<sub>1</sub>]] || {{Gene|P2RY1}} || G<sub>q/11</sub> || [[Adenosine diphosphate|ADP]]
 |- 
 | [[P2RY2|P2RY<sub>2</sub>]] || {{Gene|P2RY2}} || G<sub>q/11</sub> || [[Adenosine triphosphate|ATP]], [[Uridine triphosphate|UTP]]
 |- 
 | [[P2RY4|P2RY<sub>4</sub>]] || {{Gene|P2RY4}} || G<sub>i</sub> and G<sub>q/11</sub> || [[Uridine triphosphate|UTP]]
 |-
 | P2RY<sub>5</sub> / [[LPAR6|LPA<sub>6</sub>]] || {{Gene|LPAR6}} ||  || [[Lysophosphatidic acid]]<ref>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</ref>
 |- 
 | [[P2RY6|P2RY<sub>6</sub>]] || {{Gene|P2RY6}} || G<sub>q/11</sub> || [[Uridine diphosphate|UDP]]
 |- 
 | [[P2RY8|P2RY<sub>8</sub>]] || {{Gene|P2RY8}} ||  || [[orphan receptor]]
 |- 
 |  P2RY<sub>9</sub> /  [[LPAR4|LPAR<sub>4</sub>]] / GPR23  || {{Gene|LPAR4}} ||  || [[Lysophosphatidic acid]]
 |- 
 | [[P2RY10|P2RY<sub>10</sub>]] || {{Gene|P2RY10}} ||  || [[orphan receptor]]
 |- 
 | [[P2RY11|P2RY<sub>11</sub>]] || {{Gene|P2RY11}} || G<sub>s</sub> and G<sub>q/11</sub> || [[Adenosine triphosphate|ATP]]
 |- 
 | [[P2RY12|P2RY<sub>12</sub>]] || {{Gene|P2RY12}} || G<sub>i</sub>  || [[Adenosine diphosphate|ADP]]
 |- 
 | [[P2RY13|P2RY<sub>13</sub>]] || {{Gene|P2RY13}} || G<sub>i</sub>  || [[Adenosine diphosphate|ADP]]
 |- 
 | [[P2RY14|P2RY<sub>14</sub>]] || {{Gene|P2RY14}}  || G<sub>q/11</sub> || [[UDP-glucose]]
|}

The gaps in P2Y receptor numbering is due to that several receptors (P2Y<sub>3</sub>, P2Y<sub>5</sub>, P2Y<sub>7</sub>, P2Y<sub>8</sub>, P2Y<sub>9</sub>, P2Y<sub>10</sub>) were thought to be P2Y receptors when they were cloned, when in fact they are not.

P2Y<sub>3</sub> is the avian homologue of the mammalian P2Y<sub>6</sub>.<ref>{{cite journal | journal=Mol Pharmacol | volume=54 | issue=3 | pages=541–6 | year=1998  | author=Li Q, Olesky M, Palmer RK, Harden TK, Nicholas RA. | title=Evidence that the p2y3 receptor is the avian homologue of the mammalian P2Y6 receptor | pmid=9730913 | doi =  }}</ref>

==Clinical significance==
* P2Y<sub>2</sub> is a potential drug target for treating [[cystic fibrosis]].<ref name="pmid12458155">{{cite journal | author = Kellerman D, Evans R, Mathews D, Shaffer C | title = Inhaled P2Y<sub>2</sub> receptor agonists as a treatment for patients with Cystic Fibrosis lung disease | journal = Adv. Drug Deliv. Rev. | volume = 54 | issue = 11 | pages = 1463–74 | year = 2002 | pmid = 12458155 | doi = 10.1016/S0169-409X(02)00154-0 }}</ref>

* P2Y<sub>11</sub> is a regulator of immune response, and a common [[Polymorphism (biology)|polymorphism]] carried by almost 20% of North European [[Caucasian race|caucasians]] give increased risk of myocardial infarction, making P2Y<sub>11</sub> an interesting drug target candidate for treatment of [[myocardial infarction]].<ref name="pmid17135283">{{cite journal | author = Amisten S, Melander O, Wihlborg AK, Berglund G, Erlinge D | title = Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y<sub>11</sub> | journal = Eur. Heart J. | volume = 28 | issue = 1 | pages = 13–8 | year = 2007 | pmid = 17135283 | doi = 10.1093/eurheartj/ehl410 }}</ref>

* P2Y<sub>12</sub> is the target of the anti-platelet drug [[clopidogrel]]<ref name="pmid15199474">{{cite journal | author = Herbert JM, Savi P | title = P2Y12, a new platelet ADP receptor, target of clopidogrel | journal = Seminars in vascular medicine | volume = 3 | issue = 2 | pages = 113–22 | year = 2003 | pmid = 15199474 | doi = 10.1055/s-2003-40669 }}</ref> and other [[thienopyridine]]s.

==References==
{{Reflist|2}}

==External links==
* [http://www.biotrend.com/download/NetBTReview3-9-2008.pdf Ivar von Kügelgen: Pharmacology of mammalian P2X- and P2Y-receptors, BIOTREND Reviews No. 03, September 2008,© 2008 BIOTREND Chemicals AG]
*{{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1294 | title = P2Y Receptors | accessdate = | author = | authorlink = | coauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
*{{MeshName|Purinergic+P2+receptors}}


{{biochem-stub}}
{{G protein-coupled receptors}}
[[Category:G protein coupled receptors]]

[[pt:Receptor P2Y]]
[[sr:P2Y receptor]]
[[Category:2Fix]]