ADORA2B (Adenosine A2b Receptor) encodes the adenosine A2b receptor (A2BAR), a G protein-coupled receptor (GPCR) that stimulates adenylate cyclase activity upon ligand binding. The A2b receptor is part of the adenosine receptor family, which also includes A1, A2a, and A3 receptors. While A2a receptors are highly expressed in the brain and have been extensively studied in neurodegenerative diseases, A2b receptors are expressed at lower basal levels but are dramatically induced during inflammation and cellular stress. This induction pattern makes A2b receptors particularly relevant to the chronic neuroinflammation that characterizes Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. Located on chromosome 17p12-p11.2 in humans, the ADORA2B gene encodes a protein of approximately 44 kDa that localizes primarily to the plasma membrane. The receptor couples to Gs proteins, leading to increased cAMP production and activation of protein kinase A (PKA) and other downstream effectors. [@fredholm2011]
ADORA2B (Adenosine A2b Receptor) encodes the adenosine A2b receptor (A2BAR), a G protein-coupled receptor (GPCR) that stimulates adenylate cyclase activity upon ligand binding. The A2b receptor is part of the adenosine receptor family, which also includes A1, A2a, and A3 receptors. While A2a receptors are highly expressed in the brain and have been extensively studied in neurodegenerative diseases, A2b receptors are expressed at lower basal levels but are dramatically induced during inflammation and cellular stress. This induction pattern makes A2b receptors particularly relevant to the chronic neuroinflammation that characterizes Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. Located on chromosome 17p12-p11.2 in humans, the ADORA2B gene encodes a protein of approximately 44 kDa that localizes primarily to the plasma membrane. The receptor couples to Gs proteins, leading to increased cAMP production and activation of protein kinase A (PKA) and other downstream effectors. [@fredholm2011]
<div class="infobox infobox-protein"> [@chen2019]
<table> [@rivkees2000]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">ADORA2B Protein (Adenosine A2b Receptor)</th></tr> [@wei2018]
<tr><td><strong>Protein Name</strong></td><td>Adenosine A2b Receptor</td></tr> [@gao2020]
<tr><td><strong>Gene</strong></td><td>[ADORA2B](/genes/adora2b)</td></tr> [@liu2021]
<tr><td><strong>UniProt ID</strong></td><td>[P29274](https://www.uniprot.org/uniprot/P29274)</td></tr> [@cohen2019]
<tr><td><strong>PDB ID</strong></td><td>[3OCC](https://www.rcsb.org/structure/3OCC)</td></tr> [@hasko2008]
<tr><td><strong>Molecular Weight</strong></td><td>44 kDa (332 aa)</td></tr> [@eltzschig2012]
<tr><td><strong>Subcellular Localization</strong></td><td>Plasma membrane</td></tr> [@burnstock2016]
<tr><td><strong>Protein Family</strong></td><td>G protein-coupled receptor, Adenosine receptor family</td></tr>
<tr><td><strong>Expression</strong></td><td>Low basal, induced by inflammation</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/covid" style="color:#ef9a9a">Covid</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">45 edges</a></td>
</tr>
</table>
</div>
The adenosine A2b receptor shares the typical seven-transmembrane domain architecture of GPCRs:
Adenosine is a purine nucleoside that accumulates during cellular stress, hypoxia, and inflammation:
A2b receptors couple primarily to Gs proteins:
Under basal conditions, A2b receptor expression is low in most tissues:
A2b receptors play complex roles in neuroinflammation:
A2b receptors have been implicated in Alzheimer's disease pathogenesis:
In dopaminergic neurodegeneration:
A2b receptors are involved in demyelination and remyelination:
A2b receptors are highly induced during ischemic conditions:
Potential therapeutic applications:
Therapeutic targeting for chronic conditions:
Selective A2b receptor ligands are being developed:
A2b receptors interact with multiple proteins:
| Partner | Interaction Type |
|---------|------------------|
| Gs protein | G protein coupling |
| Beta-arrestin | Receptor internalization |
| GRK2/3 | Receptor phosphorylation |
| PKA | Downstream signaling |
| PDEs | cAMP degradation |
Studying A2b receptors in neurodegeneration:
ADORA2B polymorphisms have been associated with:
The adenosine A2b receptor represents an important link between cellular stress, inflammation, and neurodegeneration. Its induction during inflammatory conditions makes it particularly relevant to the chronic neuroinflammation seen in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. While much remains to be learned about A2b receptor function in the brain, targeting this receptor offers therapeutic potential for modulating neuroinflammation and protecting neurons from degeneration.