Adenosine receptor (AR) (AR)

Adenosine receptors are a class of G protein-coupled receptors (GPCRs) that mediate the physiological effects of extracellular adenosine, a nucleoside that acts as a cytoprotective modulator in response to cellular stress [1, 3]. The family consists of four distinct subtypes—A1, A2A, A2B, and A3—which are classified based on their primary signaling pathways: A1 and A3 typically inhibit adenylyl cyclase via Gi proteins, while A2A and A2B stimulate it via Gs proteins [6, 15]. These receptors are widely expressed throughout the body and regulate critical processes such as heart rate, neurotransmitter release, sleep-wake cycles, and immune cell function [5, 11]. In pathological states, adenosine receptors are key players in neurodegeneration, cardiovascular disorders, and the immunosuppressive environment of tumors [2, 9]. Therapeutic targeting of adenosine receptors involves both agonists and antagonists, depending on the desired clinical outcome [3, 6]. For instance, A2A antagonists like istradefylline are used to treat motor symptoms in Parkinson's disease, while A2A agonists like regadenoson are employed in cardiac stress testing [7, 11]. In oncology, blocking A2A and A2B receptors is a promising strategy to enhance anti-tumor immunity by preventing adenosine from suppressing T-cell activity [10, 17]. However, the ubiquitous distribution of these receptors presents significant challenges, as drugs must achieve high selectivity to avoid systemic side effects such as hypotension or respiratory distress [5, 9].

Other names

P1 purinoceptorP1 receptorAdenosine A1 receptor (ADORA1)Adenosine A2A receptor (ADORA2A)Adenosine A2B receptor (ADORA2B)Adenosine A3 receptor (ADORA3)

Adenosine receptors are G protein-coupled receptors that modulate intracellular cyclic AMP levels through coupling with Gi (A1, A3) or Gs (A2A, A2B) proteins. Drugs targeting these receptors act as agonists or antagonists to modulate downstream signaling pathways involved in neurotransmission, cardiovascular function, and immune regulation [1, 3, 6].