Adenosine receptor A1 (A1R) (A1R)

The Adenosine receptor A1 (A1R) is a high-affinity G protein-coupled receptor (GPCR) that mediates the inhibitory physiological actions of adenosine in the central nervous system (CNS) and peripheral tissues (UniProt P25103). In the rat CNS, A1R is widely expressed and acts as a potent neuromodulator by inhibiting the presynaptic release of excitatory neurotransmitters like glutamate and hyperpolarizing postsynaptic neurons (NIH, 1.4.3). This inhibitory tone provides significant neuroprotection during metabolic stress, such as ischemia or hypoxia, by reducing excitotoxic damage (NIH, 1.2.3). In the cardiovascular system, A1R activation leads to negative chronotropic and inotropic effects, which can protect the heart during ischemia but also pose risks of bradycardia and heart block (Frontiers, 1.2.1). The receptor primarily signals through Gi/Go proteins to inhibit adenylyl cyclase, thereby reducing intracellular cAMP levels and modulating ion channel activity (NIH, 1.1.5). While A1R is a promising therapeutic target for treating pain, arrhythmias, and heart failure, clinical progress has been hindered by on-target side effects and the complexity of its widespread expression (MDPI, 1.2.4).

Other names

Adora1A1 adenosine receptorA1ARPurinergic receptor P1

Agonist binding to the A1 receptor activates Gi/Go-type G proteins, which inhibit adenylyl cyclase activity, leading to a decrease in intracellular cAMP levels. This signaling cascade also involves the activation of G protein-coupled inwardly rectifying potassium (GIRK) channels and the inhibition of N-type and P/Q-type voltage-gated calcium channels, resulting in cellular hyperpolarization and reduced neurotransmitter release.