Central adenosine A2A receptors: an overview

Recent advances in molecular biology, biochemistry, cell biology and behavioral pharmacology together with the development of more selective ligands to the various adenosine receptors have increased our understanding of the functioning of central adenosine A_2A receptors. The A_2A receptor is one of four adenosine receptors found in the brain. Its expression is highest in striatum, nucleus accumbens and olfactory tubercles, although it also occurs in neurons and microglia in most other brain regions. The receptor has seven transmembrane domains and couples via Gs to adenyl cyclase stimulation. Antagonistic interactions between A_2A receptors and dopamine D₂ receptors have been described, as stimulation of the A_2A receptor leads to a reduction in the affinity of D₂ receptors for D₂ receptor agonists. The A_2A receptor is thought to play a role in a number of physiological responses and pathological conditions. Indeed, A_2A receptor antagonists may be useful for the treatment of acute and chronic neurodegenerative disorders such as cerebral ischemia or Parkinson's disease. A_2A receptor agonists may treat certain types of seizures or sleep disorders. This review discusses the characteristics, distribution, pharmacochemical properties and regulation of central A_2A receptors, as well as A_2A receptor-mediated behavioural responses and their potential role in various neuropsychiatric disorders.