ADORA1

ADORA1 encodes the adenosine A1 receptor, a G protein–coupled receptor that binds adenosine and mediates diverse physiological effects. The A1 receptor is expressed in the brain and, to a lesser extent, in peripheral tissues such as the heart and kidney, with highest signaling influence in the central nervous system.

Upon activation, the A1 receptor primarily couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP levels. This signaling also promotes the opening of GIRK potassium channels and dampens voltage-gated calcium entry, leading to decreased neuronal excitability.

Physiological roles include suppression of neurotransmitter release, promotion of sleep, and protection during metabolic stress or ischemia in the brain. In the heart, A1 receptor activation can slow heart rate and conduction. Peripheral effects include modulation of renal and other tissue functions.

In pharmacology, ADORA1 ligands are used to study receptor function. Agonists mimic native adenosine, while selective antagonists block A1 activity. The receptor is investigated for neuroprotection, analgesia, and cardiovascular safety, though systemic activation can have bradycardic side effects.

Evolutionarily conserved across mammals and other vertebrates, ADORA1 reflects the important role of adenosine signaling in coordinating energy state and neural activity.