Adenosine A2A receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons (original) (raw)
Summary
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 AZA receptor selective agonist CGS 21680. The non-selective adenosine receptor antagonist 8-(p-sulphophenyl)-theophylline and the AZA receptor selective antagonist 8-(3chlorostyryl) caffeine abolished the inhibitory action of CGS 21680. Intracellular GDP-_β_-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, AZA 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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Authors and Affiliations
- Department of Pharmacology, University of Freiburg, Germany
W. N örenberg - Department of Pharmacology, University of Leipzig, Härtelstrasse 16-18, D-04107, Leipzig, Germany
K. Wirkner, H. Aßmann, M. Richter & P. Illes
Authors
- W. N örenberg
- K. Wirkner
- H. Aßmann
- M. Richter
- P. Illes
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N örenberg, W., Wirkner, K., Aßmann, H. et al. Adenosine A2A receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons.Amino Acids 14, 33–39 (1998). https://doi.org/10.1007/BF01345239
- Received: 25 August 1997
- Accepted: 26 September 1997
- Issue date: March 1998
- DOI: https://doi.org/10.1007/BF01345239