The adenosine A
3 receptor, also known as ADORA3, is an
adenosine receptor, 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 ba ...
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 c ...
, 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 in ...
degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulo ...
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 involv ...
.
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 wi ...
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)
* CF-102
* 2-Cl-IB-MECA
*
CP-532,903
*
Inosine[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
* 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
PSB-10 is a drug which acts as a selective antagonist for the adenosine A3 receptor (ki value at human A3 receptor is 0.44 nM), with high selectivity over the other three adenosine receptor subtypes (ki values at human A1, A2A and A2B recepto ...
References
Further reading
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External links
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{{Adenosinergics
Adenosine receptors