Adenosine A2A receptor enhances GABAA-mediated IPSCs in the rat globus pallidus

Authors


Corresponding author
M. Ichimura: Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd, 1188 Shimotogari, Nagaizumi, Sunto, Shizuoka 411-8731, Japan.

Abstract

  • 1The actions of adenosine A2A receptor agonists were examined on GABAergic synaptic transmission in the globus pallidus (GP) in rat brain slices using whole-cell patch-clamp recording. GP neurones were characterized into two major groups, type I and type II, according to the degree of time-dependent hyperpolarization-activated inward rectification and the size of input resistance.
  • 2The A2A receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamido- adenosine (CGS21680; 0.3-3 μm) enhanced IPSCs evoked by stimulation within the GP. The actions of CGS21680 were blocked by the A2A antagonists (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385).
  • 3The CGS21680-induced increase in IPSCs was associated with a reduction in paired-pulse facilitation. CGS21680 (0.3 μm) increased the frequency of miniature IPSCs (mIPSCs) without affecting mIPSC amplitude. These observations demonstrated that the enhancement of IPSCs in the GP was attributable to presynaptic, but not postsynaptic, A2A receptors.
  • 4The results suggest that A2A receptors in the GP serve to inhibit GP neuronal activity, thereby disinhibiting subthalamic nucleus neurone activity. Thus, the A2A receptor-mediated presynaptic regulation in the GP, together with the A2A receptor-mediated intrastriatal presynaptic control of GABAergic neurotransmission described previously, may play a crucial role in controlling the neuronal functions of basal ganglia. This A2A receptor-mediated presynaptic dual control in the striatopallidal pathway could also afford the mode of action of A2A antagonists for ameliorating the symptoms of Parkinson's disease in an animal model.

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