The adenosine A₃ receptor, also known as ADORA3, is an adenosine receptor

Adenosine receptor

The adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...

, but also denotes the human gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 encoding it.

Function

Adenosine A₃ receptors are 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 that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. It mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death.

Therapeutic implications

An adenosine A₃ receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis

Rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

.
In a mouse model of infarction the A₃ selective agonist CP-532,903

CP-532,903

CP-532,903 is a selective adenosine A3 subtype receptor agonist. It has antiinflammatory effects and has been shown to reduce superoxide generation in damaged tissues, and protects against tissue damage following myocardial ischemia, mediated via an interaction with ATP-sensitive potassium channels....

 protected against myocardial ischemia

Ischemia

In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

 and reperfusion injury.

Agonists/Positive Allosteric Modulators

• 2-(1-Hexynyl)-N-methyladenosine
• CF-101 (IB-MECA)
• CF-102
• 2-Cl-IB-MECA
• CP-532,903
  CP-532,903
  CP-532,903 is a selective adenosine A3 subtype receptor agonist. It has antiinflammatory effects and has been shown to reduce superoxide generation in damaged tissues, and protects against tissue damage following myocardial ischemia, mediated via an interaction with ATP-sensitive potassium channels....
  
  
• Inosine
• LUF-6000
• MRS-3558

Antagonists/Negative Allosteric Modulators

• KF-26777
  KF-26777
  KF-26777 is a drug which acts as a potent and selective antagonist for the adenosine A3 receptor, with sub-nanomolar affinity and high selectivity over the other three adenosine receptor subtypes...
  
  
• MRS-545
• MRS-1191
• MRS-1220
• MRS-1334
• MRS-1523
• MRS-3777
• MRE-3005-F20
• MRE-3008-F20
• PSB-11
• OT-7999
• VUF-5574

External links