Adenosine receptors are found throughout the central nervous system; however, type A2A receptors are seen almost exclusively on gamma-aminobutyric acid
(GABA), enkephalin, and cholinergic (ACh) spiny neurons in the striatum. These neurons receive inhibitory dopaminergic input from the substantia nigra and then project to inhibit pallidal neurons as part of the indirect pathway of the basal ganglia. Therefore, in PD, dopaminergic cell loss results in disinhibition of striatal spiny neurons that subsequently overly inhibit the globus pallidus externus, which in turn overly stimulate the subthalamic and globus pallidus internus nuclei. This increased activity in the final basal ganglia outflow pathway finalizes PD symptoms. Antagonism of the adenosine A2A receptor appears to modulate GABA and ACh release in a manner that could counteract the deleterious effects of reduced dopaminergic stimulation (27).
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