Adenosine A1 receptor and Adenosine A2A receptor (A1AR and A2AAR)

Adenosine A1 receptor and Adenosine A2A receptor are members of the G protein-coupled receptor superfamily that mediate the physiological actions of adenosine, an endogenous purine nucleoside involved in cellular signaling. A1AR is widely distributed in the brain, heart, and adipose tissue, where it mainly inhibits adenylyl cyclase via Gi/Go proteins, leading to neuronal inhibition, decreased heart rate, and metabolic regulation. A2AAR is highly expressed in the brain (especially striatum) and immune cells and stimulates adenylyl cyclase via Gs proteins, mediating vasodilation, suppression of inflammatory responses, and modulation of immune cell activity. Drugs targeting these receptors are in clinical use or clinical trials for cardiovascular diseases, neurological disorders, and cancer, but their ubiquitous expression poses challenges for drug selectivity and adverse effect minimization.

Other names

A1 adenosine receptorA1ARA2A adenosine receptorA2AAR

A1 receptor agonists decrease heart rate, inhibit neurotransmitter release, and increase cytoprotection. A2A receptor agonists induce vasodilation, provide immunosuppression, act as anti-inflammatory agents, and offer neuroprotection. Conversely, antagonists targeting A1 and/or A2A receptors exhibit stimulant action (e.g., caffeine), neuroprotective effects, and anti-angiogenic properties.