New aspects of physiological and pathophysiological functions of adenosine A2A receptor in basal ganglia

There is now growing interest in the functional role of adenosine A(2A) receptors. Their distribution within the brain is restricted in the basal ganglia, particularly abundant in the striatum, which are thought to play a crucial role in the control of motor behavior. Indeed, newly developed A(2A) receptor selective antagonists have a profound influence on motor functions, with anti-Parkinsonian activities in several animal models. Striatal spiny neurons serve as a major anatomical locus for the relay of cortical information flow through the basal ganglia. The GABA releasing projection neurons represent the A(2A) receptor-mediated main target of adenosine. The GABAergic synaptic neurotransmission is regulated by adenosine via A(2A) receptors on the presynaptic terminals. Blockade of this modulatory function by A(2A) antagonists could repair striatopallidal abnormal neuronal activities provoked by striatal dopamine depletion in the Parkinsonian state. A(2A) receptor antagonists provide a novel therapeutic potential for the treatment of Parkinson's disease.