1. Academic Validation
  2. Adenosine A2A receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons

Adenosine A2A receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons

  • Amino Acids. 1998;14(1-3):33-9. doi: 10.1007/BF01345239.
W Nörenberg 1 K Wirkner H Assmann M Richter P Illes
Affiliations

Affiliation

  • 1 Department of Pharmacology, University of Freiburg, Federal Republic of Germany.
Abstract

Whole-cell patch clamp experiments were carried out in rat striatal brain slices. In a subset of striatal neurons (70-80%), NMDA-induced inward currents were inhibited by the adenosine A2A receptor selective agonist CGS 21680. The non-selective Adenosine Receptor Antagonist 8-(p-sulphophenyl)-theophylline and the A2A receptor selective antagonist 8-(3-chlorostyryl)caffeine abolished the inhibitory action of CGS 21680. Intracellular GDP-beta-S, which is known to prevent G protein-mediated reactions, also eliminated the effect of CGS 21680. Extracellular dibutyryl cAMP, a membrane permeable analogue of cAMP, and intracellular Sp-cAMPS, an activator of cAMP-dependent protein kinases (PKA), both abolished the CGS 21680-induced inhibition. By contrast, Rp-cAMPS and PKI 14-24 amide, two inhibitors of PKA had no effect. Intracellular U-73122 (a Phospholipase C Inhibitor) and heparin (an inositoltriphosphate antagonist) prevented the effect of CGS 21680. Finally, a more efficient buffering of intracellular Ca2+ by a substitution of EGTA (11 mM) by BAPTA (5.5 mM) acted like U-73122 or heparin. Hence, A2A receptors appear to negatively modulate NMDA Receptor channel conductance via the Phospholipase C/inositoltriphosphate/Ca2+ pathway rather than the Adenylate Cyclase/PKA pathway.

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