A1 Receptor

The A1 receptor, or A1 adenosine receptor, is a cell-surface receptor that responds to the signaling molecule adenosine. It is one of four known adenosine receptor subtypes, alongside A2A, A2B, and A3. All four belong to the G-protein-coupled receptor family but differ in their intracellular signaling and can therefore produce different physiological effects .¹

The A1 receptor couples predominantly to inhibitory Gi/o proteins. When adenosine activates the receptor, this signaling commonly inhibits adenylyl cyclase and reduces production of cyclic AMP (cAMP). A1 receptor activation can also regulate ion channels and other signaling pathways, with the exact response depending on the cell type and tissue .^1,2

A1 receptors are widely distributed, including in the brain, heart, kidneys, and other tissues. In the nervous system, their activation can reduce neuronal excitability and neurotransmitter release. In the heart, A1 receptor signaling can slow heart rate and conduction through the atrioventricular node. These effects illustrate how the same receptor can regulate different processes depending on where it is expressed .^1,2

The A1 receptor is distinct from the A2A receptor, another adenosine receptor subtype. A1 receptors generally signal through Gi/o proteins and reduce adenylyl cyclase activity, whereas A2A receptors primarily couple to stimulatory G proteins and increase cAMP production. Compounds that block A1 receptors are called A1 receptor antagonists, while substances that activate them are A1 receptor agonists .¹