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 chemorece ...
for
adenosine diphosphate
Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbon ...
(ADP)
that belongs to the
Gi class of a group of
G protein-coupled (GPCR)
purinergic receptors.
This
P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various
adenosine
Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...
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 nuc ...
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
s. The P2Y
12 receptor is involved in
platelet aggregation
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...
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
thromboembolisms 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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
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 is com ...
platelet
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
s, and is an important regulator in blood
clotting.
In the central nervous system, this receptor has been found expressed exclusively on
microglia
Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...
, where it is necessary for physiological and pathological microglial actions, such as monitoring neuronal functions and microglial neuroprotection.
P2Y12 antagonists
The drugs
clopidogrel
Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet drug, antiplatelet medication used to reduce the risk of Cardiovascular disease, heart disease and stroke in those at high risk. It is also used together with aspi ...
(Plavix),
prasugrel
Prasugrel, sold under the brand names Effient and Efient, 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 of the thienopyridine drug class. It ...
(Efient, Effient),
ticagrelor (Brilinta), and
cangrelor (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 () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
, called dual antiplatelet treatment, remains the first-line treatment for
acute coronary syndrome
Acute coronary syndrome (ACS) is a syndrome due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally located pressure-like chest pain, ...
. A 2019 randomized trial suggested that prasugrel is superior to ticagrelor.
Antiplatelet treatment of STEMI
In patients undergoing primary
percutaneous coronary intervention
Percutaneous coronary intervention (PCI) is a minimally invasive non-surgical procedure used to treat stenosis, narrowing of the coronary artery, coronary arteries of the heart found in coronary artery disease. The procedure is used to place and ...
(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). 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 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
{{Purinergics
G protein-coupled receptors