P2Y
12 is a
chemoreceptor
A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecept ...
for
adenosine diphosphate (ADP)
that belongs to the
Gi class of a group of
G protein-coupled
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPCR)
purinergic receptors.
This
P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various
adenosine and
uridine
Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1-glycosidic bond. The analog is one of the five standard nucleosides which make up nucle ...
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
s. The P2Y
12 receptor is involved in
platelet aggregation
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
and is thus a
biological target
A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...
for the treatment of
thromboembolism
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (t ...
s and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.
In the field of
purinergic signaling, the P2Y
12 protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
on the periphery is found mainly but not exclusively on the surface of
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
s, and is an important regulator in blood
clotting
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
.
In the central nervous system, this receptor has been found expressed exclusively on
microglia, where it is necessary for physiological and pathological microglial actions, such as monitoring neuronal functions and microglial neuroprotection.
P2Y12 inhibitors
The drugs
clopidogrel
Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following ...
(Plavix),
prasugrel
Prasugrel, sold under the brand name Effient in the US, Australia and India, and Efient in the EU) is a medication used to prevent formation of blood clots. It is a platelet inhibitor and an irreversible antagonist of P2Y12 ADP receptors and is ...
(Efient, Effient),
ticagrelor
Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It ...
(Brilinta), and
cangrelor
Cangrelor, sold under the brand name Kengreal in the United States, CANREAL in India ( MSN Labs ) and Kengrexal in the European Union) is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P ...
(Kengreal) bind to this receptor and are marketed as
antiplatelet agents.
For acute coronary syndrome
The combination of a P2Y
12 inhibitor and
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
, called dual antiplatelet treatment, remains the first-line treatment for
acute coronary syndrome. A 2019 randomized trial suggested that prasugrel is superior to ticagrelor.
Antiplatelet treatment of STEMI
In patients undergoing primary
percutaneous coronary intervention (PCI) for an ST-segment elevation myocardial infarction (STEMI), US,
European,
and Canadian
guidelines recommend that a P2Y
12 inhibitor should be administered as soon as possible, although it is unclear whether administration of these medications before the patient arrives at the hospital confers additional benefits compared with in-hospital administration.
On the other hand, P2Y
12 inhibitors do not change the risk of death when given as a pretreatment prior to routine PCI in people who have had a non-ST-elevation myocardial infarction (
NSTEMI
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tra ...
). Though, a P2Y
12 inhibitor in addition to aspirin should be administered for up to 12 months to most patients with non-ST-elevation acute coronary syndrome. They do however increase the risk of bleeding and decrease the risk of further cardiovascular problems. Thus their routine use in this context is of questionable value.
A
network meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of 37 studies involving 88,402 STEMI patients and 5,077
major adverse cardiac events (MACE) patients found that use of prasugrel was associated with lower mortality and MACE than other drugs in this class (clopidogrel and ticagrelor).
References
External links
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{{Purinergics
G protein-coupled receptors