P2Y receptor
Encyclopedia
P2Y receptors are a family of purinergic receptor
s, G protein-coupled receptor
s stimulated by nucleotide
s 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
.
P2Y receptors are present in almost all human tissues where they exert various biological functions based on their G-protein coupling.
, Gq/11 or Gs G proteins. Human P2Y receptors have the following G protein coupling:
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.
Purinergic receptor
Purinergic receptors, also known as purinoceptors, are a family of newly characterized plasma membrane molecules involved in several cellular functions such as vascular reactivity, apoptosis and cytokine secretion...
s, G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
s stimulated by nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s such as ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
, UTP, UDP
Uridine diphosphate
Uridine diphosphate, abbreviated UDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil.-See also:* Nucleoside...
and UDP-glucose. To date, 12 P2Y receptors have been cloned in humans: P2Y1
P2RY1
P2Y purinoceptor 1 is a protein that in humans is encoded by the P2RY1 gene.-Further reading:...
, P2Y2
P2RY2
P2Y purinoceptor 2 is a protein that in humans is encoded by the P2RY2 gene.-Further reading:...
, P2Y4
P2RY4
P2Y purinoceptor 4 is a protein that in humans is encoded by the P2RY4 gene.-Further reading:...
, P2Y5
P2RY5
Lysophosphatidic acid receptor 6 also known as LPA6 and P2RY5 is a protein that in humans is encoded by the LPAR6 gene. LPA6 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid ....
, P2Y6
P2RY6
P2Y purinoceptor 6 is a protein that in humans is encoded by the P2RY6 gene.-Further reading:-External links:...
, P2Y8
P2RY8
P2Y purinoceptor 8 is a protein that in humans is encoded by the P2RY8 gene.-Further reading:...
, P2Y9
GPR23
Lysophosphatidic acid receptor 4 also known as LPA4 is a protein that in humans is encoded by the LPAR4 gene. LPA4 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid .-Further reading:...
(present in NCBI as GPR23), P2Y10
P2RY10
Putative P2Y purinoceptor 10 is a protein that in humans is encoded by the P2RY10 gene.-Further reading:...
, P2Y11
P2RY11
P2Y purinoceptor 11 is a protein that in humans is encoded by the P2RY11 gene.-Further reading:...
, P2Y12, P2Y13
P2RY13
P2Y purinoceptor 13 is a protein that in humans is encoded by the P2RY13 gene.-Further reading:...
and P2Y14
P2RY14
P2Y purinoceptor 14 is a protein that in humans is encoded by the P2RY14 gene.-Further reading:...
.
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 GiGi alpha subunit
Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors...
, Gq/11 or Gs G proteins. Human P2Y receptors have the following G protein coupling:
| Protein | Gene | Coupling | Nucleotide Nucleotide Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions... >- | P2RY1 P2RY1 P2Y purinoceptor 1 is a protein that in humans is encoded by the P2RY1 gene.-Further reading:... |
Gq/11 | ADP Adenosine diphosphate Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine.... >- | P2RY2 P2RY2 P2Y purinoceptor 2 is a protein that in humans is encoded by the P2RY2 gene.-Further reading:... |
Gq/11 | ATP Adenosine triphosphate Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism... , UTP >- | P2RY4 P2RY4 P2Y purinoceptor 4 is a protein that in humans is encoded by the P2RY4 gene.-Further reading:... |
Gi and Gq/11 | >- | Lysophosphatidic acid Lysophosphatidic acid Lysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3... >- | P2RY6 P2RY6 P2Y purinoceptor 6 is a protein that in humans is encoded by the P2RY6 gene.-Further reading:-External links:... |
Gq/11 | UDP Uridine diphosphate Uridine diphosphate, abbreviated UDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil.-See also:* Nucleoside... >- | P2RY8 P2RY8 P2Y purinoceptor 8 is a protein that in humans is encoded by the P2RY8 gene.-Further reading:... |
orphan receptor Orphan receptor An orphan receptor is an apparent receptor that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan".-Examples:Examples of orphan... >- | P2RY9 / LPAR4 / GPR23 |
Lysophosphatidic acid Lysophosphatidic acid Lysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3... >- | P2RY10 P2RY10 Putative P2Y purinoceptor 10 is a protein that in humans is encoded by the P2RY10 gene.-Further reading:... |
orphan receptor Orphan receptor An orphan receptor is an apparent receptor that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan".-Examples:Examples of orphan... >- | P2RY11 P2RY11 P2Y purinoceptor 11 is a protein that in humans is encoded by the P2RY11 gene.-Further reading:... |
Gs and Gq/11 | ATP Adenosine triphosphate Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism... >- | P2RY12 |
Gi | ADP Adenosine diphosphate Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine.... >- | P2RY13 P2RY13 P2Y purinoceptor 13 is a protein that in humans is encoded by the P2RY13 gene.-Further reading:... |
Gi | ADP Adenosine diphosphate Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine.... >- | P2RY14 P2RY14 P2Y purinoceptor 14 is a protein that in humans is encoded by the P2RY14 gene.-Further reading:... |
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 fibrosisCystic fibrosisCystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
.
- P2Y11 is a regulator of immune response, and a common polymorphismPolymorphism (biology)Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
carried by almost 20% of North European caucasiansCaucasian raceThe term Caucasian race has been used to denote the general physical type of some or all of the populations of Europe, North Africa, the Horn of Africa, Western Asia , Central Asia and South Asia...
give increased risk of myocardial infarction, making P2Y11 an interesting drug target candidate for treatment of myocardial infarctionMyocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
.
- P2Y12 is the target of the anti-platelet drug clopidogrelClopidogrelClopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
and other thienopyridineThienopyridineThienopyridines are a class of ADP receptor/P2Y12 inhibitors used for their anti-platelet activity.-Examples:These drugs include:Prasugrel ,Ticlopidine ,Clopidogrel ....
s.