A₁ Adenosine Receptor Activation Modulates Central Nervous System Development and Repair

Adenosine is an endogenous, autacoid purine nucleoside which performs many important biological roles, particularly during stressful events. Adenosine can signal through four adenosine receptor (AR) subtypes: A₁, A_2A, A_2B, and A₃. Of these, adenosine A₁ receptor (A₁AR) has a broad, wide distribution throughout different vertebrate cell types and the highest affinity to adenosine. The A₁AR-dependent action of adenosine is well documented in reports from numerous studies that have used different selective A₁AR agonists and antagonists as well as in animals that have a genetically manipulated A₁AR gene. Despite its wide distribution and function, A₁AR homo/hetero-oligomerization with other adenosine and non-adenosine receptors extends its biological role during developmental, physiological, and pathological situations. In this review, we initially discuss the A₁AR structure and most important signaling pathway triggered by its activation. Next, we summarize some of the most well-known biological effects of A₁AR in the central nervous system (CNS) during development and adulthood, in addition to its role in nervous system regeneration and repair.