The adenosine A
3 receptor, also known as ADORA3, is an
adenosine receptor
The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. There are four known types of adenosine receptors in humans: A1, A2A, A2B and A3; each is encoded by a di ...
, but also denotes the human
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
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 p ...
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
Coronary ischemia, myocardial ischemia, or cardiac ischemia,Potochny, Evy. "Cardiac Ischemia Symptoms." LiveStrong. Demand Media, 9 March 2010. Web. 6 Nov. 2010. is a medical term for a reduced blood flow in the coronary circulation through the ...
, it is involved in the inhibition of
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
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 joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...
.
In a mouse model of infarction the A
3 selective agonist
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
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formu ...
protected against myocardial
ischemia and
reperfusion injury
Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + ''perfusion'') after a period of ischemia or lack of oxygen (anoxia or hy ...
.
Selective Ligands
A number of selective A
3 ligands are available.
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 is a selective adenosine A3 subtype receptor agonist. It has antiinflammatory effects and has been shown to reduce superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formu ...
*
Inosine
Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring (also known as a ribofuranose) via a β-N9- glycosidic bond. It was discovered in 1965 in analysis of RNA transferase.
Inosine is commonly found in tRNAs and is ...
[Xiaowei Jin, Rebecca K. Shepherd, Brian R. Duling, and Joel Linden]
"Inosine Binds to A3 Adenosine Receptors and Stimulates Mast Cell Degranulation"
/ref>
* LUF-6000
* MRS-3558
* AST-004
Antagonists/Negative Allosteric Modulators
* KF-26777
KF-26777 is a drug which acts as a potent and selective antagonist for the adenosine A3 receptor, with sub-nanomolar affinity (A3 Ki=0.2nM) and high selectivity over the other three adenosine receptor subtypes. Simple xanthine derivatives such ...
* 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
Inverse Agonists
* PSB-10
References
Further reading
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External links
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{{Adenosinergics
Adenosine receptors