Abstract
Taurine has neuroprotective capabilities against glutamate-induced excitotoxicity through several identified mechanisms including opening of the Cl−channel associated with GABAAand glycine receptors, or a distinct Cl−channel. No existing work has however shown a direct interaction of taurine with the glutamate NMDA receptor. Here we demonstrate such direct interactions using electrophysiological and receptor binding techniques on rat medial prefrontal cortical (mPFC) slices and well-washed rat cortical membrane. Electrically evoked field potential responses were recorded in layer 4/5 of mPFC in the presence of picrotoxin to prevent opening of Cl−channels gated by GABA or taurine. Applied taurine markedly diminished evoked-response amplitude at the peak and latter phases of the response. These phases were predominantly sensitive to the NMDA antagonist, MK-801, but not the AMPA/kainate receptor antagonist CNQX. Furthermore, this taurine effect was blocked by APV pretreatment. Taurine (0.1 mM) decreased spermine-induced enhancement of specific (3H) MK-801 binding to rat cortical membrane in the presence of glycine, though it was ineffective in the absence of spermine. Our preliminary work shows that taurine diminished the apparent affinity of NMDA receptor to glycine in the presence of spermine. These results indicate that taurine may directly interact with the NMDA receptor through multiple mechanisms.
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- AMPA:
-
(RS)-α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- ACSF:
-
Artificial cerebral spinal fluid
- APV:
-
Dl-2-Amino-5-phosphonopentanoic acid
- CNQX:
-
6-Cyano-7-nitroquinoxaline-2,3-dione
- GABA:
-
Gamma-aminobutyric acid
- mPFC:
-
Medial prefrontal cortex
- NMDA:
-
N-Methyl-d-aspartate
- TAG:
-
6-Aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
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Acknowledgements
This work was supported by DA018055 grant from NIDA and by a PSCCUNY-award 63679-0041.
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© 2013 Springer Science+Business Media New York
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Chan, C.Y. et al. (2013). Direct Interaction of Taurine with the NMDA Glutamate Receptor Subtype via Multiple Mechanisms. In: El Idrissi, A., L'Amoreaux, W. (eds) Taurine 8. Advances in Experimental Medicine and Biology, vol 775. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6130-2_4
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DOI: https://doi.org/10.1007/978-1-4614-6130-2_4
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