Adenosine A(2A) receptor enhances GABA(A)-mediated IPSCs in the rat globuspallidus

1. The actions of adenosine ASA receptor agonists were examined on GABAergi c synaptic transmission in the globus pallidus (GP) in rat brain slices usi ng whole-cell patch-clamp recording. GP neurones were characterized into tw o major groups, type I and type II, according to the degree of time-depende nt hyperpolarization-activated inward rectification and the size of input r esistance. 2. The A(2A) receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-eth ylcarboxamido-adenosine (CGS21680; 0.3-3 muM) enhanced IPSCs evoked by stim ulation within the GP. The actions of CGS21680 were blocked by the A(2), an tagonists (E)-8-(3,4-dimethoxystyryl)-1,3dipropyl-7-methylxanthine (KF17837 ) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylami no]ethyl)phenol (ZM241385). 3. The CG-S21680-induced increase in IPSCs was associated with a reduction in paired-pulse facilitation. CGS21680 (0.3 muM) increased the frequency of miniature IPSCs (mIPSCs) without affecting mIPSC amplitude. These observat ions demonstrated that the enhancement of IPSCs in the GP was attributable to presynaptic, but not postsynaptic, A(2), receptors. 4. The results suggest that A(2A) receptors in the GP serve to inhibit GP n euronal activity, thereby disinhibiting subthalamic nucleus neurone activit y. Thus, the A(2A) receptor-mediated presynaptic regulation in the GP, toge ther with the A(2A) receptor-mediated intrastriatal presynaptic control of GABAergic neurotransmission described previously, may play a crucial role i n controlling the neuronal functions of basal ganglia. This A(2A) receptor- mediated presynaptic dual control in the striatopallidal pathway could also afford the mode of action of A(2A) antagonists for ameliorating the sympto ms of Parkinson's disease in an animal model.