The adenosine A
3 receptor, also known as ADORA3, is an
adenosine receptor
The adenosine receptors (or P1 receptors) are a class of Purinergic receptor, purinergic G protein-coupled receptors with adenosine as the endogenous ligand (biochemistry), ligand. There are four known types of adenosine receptors in humans: Aden ...
, but also denotes the human
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
encoding it.
Function
Adenosine A
3 receptors are
G protein-coupled receptor
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 ...
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
Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
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.
Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18).
Gene
Multiple transcript variants encoding different isoforms have been found for this gene.
Therapeutic implications
An adenosine A
3 receptor agonist (CF-101) is in clinical trials for the treatment of
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
.
In a mouse model of infarction the A
3 selective agonist
CP-532,903 protected against myocardial
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
and
reperfusion injury.
Selective Ligands
A number of selective A
3 ligands are available.
Agonists/Positive Allosteric Modulators
*
2-(1-Hexynyl)-N-methyladenosine
*
CF-101 (
IB-MECA)/
Piclidenoson
*
CF-102 (
2-Cl-IB-MECA)/
Namodenoson
*
CP-532,903
*
Inosine
*
LUF6000[Courtney L. Fisher, Matteo Pavan, Veronica Salmaso, Robert F. Keyes, Tina C. Wan, Balaram Pradhan, Zhan-Guo Gao, Brian C. Smith, Kenneth A. Jacobson and John A. Auchampach. https://doi.org/10.1124/molpharm.123.000784> "Extrahelical binding site for a 1H-imidazo[4,5-cuinolin-4-amine A3 adenosine receptor positive allosteric modulator on helix 8 and distal portions of transmembrane domains 1 and 7"]]
* MRS-3558
* MRS7292
* AST-004
* CF 602
Antagonists/Negative Allosteric Modulators
* KF-26777
* MRS-545
* MRS-1191
* MRS-1220
* MRS-1334
* MRS-1523
* MRS-3777
* MRE-3005-F20
* MRE-3008-F20
* PSB-11
* OT-7999
* VUF-5574
* SSR161421
* ISAM-DM10
Inverse Agonists
*
PSB-10
References
Further reading
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External links
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{{Adenosinergics
Adenosine receptors