Adenosine A1 receptor (ADORA1)

The Adenosine A1 receptor is a high-affinity G protein-coupled receptor (GPCR) that is highly expressed throughout the central nervous system, particularly in the rat brain's hippocampus, cortex, and cerebellum (UniProt P25103). It primarily signals through Gi/o proteins to inhibit adenylate cyclase, resulting in decreased intracellular cAMP levels and the subsequent modulation of potassium and calcium channels (IUPHAR/BPS Guide to Pharmacology). This signaling pathway leads to a general inhibition of neuronal firing and the suppression of excitatory neurotransmitter release, such as glutamate, providing a potent neuroprotective mechanism during metabolic stress or hypoxic events (PubMed PMID: 11036155). In clinical contexts, the receptor is a target for treating epilepsy, neuropathic pain, and sleep disturbances, although its widespread expression in the heart and kidneys can lead to dose-limiting side effects like bradycardia (PubMed PMID: 21530123). Common ligands include the non-selective antagonist caffeine, which promotes wakefulness by blocking the inhibitory effects of endogenous adenosine, and various synthetic agonists being explored for their cardioprotective and analgesic properties (PubChem CID 2519).

Other names

A1ARAdenosine receptor A1A1 adenosine receptorR-PIA receptor

Agonists bind to the receptor and activate Gi/o proteins, which inhibits adenylate cyclase activity and reduces cAMP levels, while antagonists block the binding of endogenous adenosine to prevent these inhibitory effects.