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Eur J Pharmacol. 2014 Apr 5;728:167-75. doi: 10.1016/j.ejphar.2014.01.025. Epub 2014 Jan 28.

Modes of direct modulation by taurine of the glutamate NMDA receptor in rat cortex.

Author information

1
Department of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education at CCNY, City University of New York, New York, NY 10031, USA; Neuroscience Subprogram, Doctoral Programs in Biology, Graduate Center of the City University of New York, NY 10016, USA.
2
Department of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education at CCNY, City University of New York, New York, NY 10031, USA.
3
Department of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education at CCNY, City University of New York, New York, NY 10031, USA; Department of Biology, Bronx Community College, the City University of New York, The Bronx, NY 10453, USA.
4
Department of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education at CCNY, City University of New York, New York, NY 10031, USA; Neuroscience Subprogram, Doctoral Programs in Biology, Graduate Center of the City University of New York, NY 10016, USA. Electronic address: Banerjee@med.cuny.edu.

Abstract

Taurine is an endogenous brain substance with robust neuromodulatory and possible neuroprotective properties. Though other mechanisms of action have been reported, its interaction with the NMDA (N-methyl-D-aspartic acid) receptor is undocumented. We investigated taurine's interaction with the NMDA receptor using electrophysiological and receptor binding approaches. The effects of taurine on field potential responses in layer-5 of prelimbic cortex in rat brain slices evoked by single-pulse electrical stimulation of ventral medial cortex were determined. Picrotoxin (80 µM) was present in all control and drug solutions to block the Cl(-) channels associated with the GABA-, taurine-, and strychnine sensitive glycine- receptors. A typical response consisted of an NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]-quinoxaline-7-sulfonamide)-sensitive negative wave (N1) followed by a positive wave (P1) and a broad negativity (N2), both sensitive to dl-AP5 (dl-2-amino-5-phosphonopentanoic acid) inhibition. Taurine exerted a 41.5 ± 8.3% (n = 9) voltage reduction within the late phase of N2. This taurine action was prevented by 100 µM AP5, but not by 10 µM nifedipine, supporting a direct modulation of NMDA receptor function by taurine, without requiring the involvement of the L-type Ca(2+) channel. Taurine did not alter specific [(3)H] MK-801 binding to rat cortical membranes in the presence of glycine or glutamate; but inhibited spermine-potentiated specific [(3)H] MK-801 binding to NMDA receptors by 15-20% in the presence of glycine. In addition, taurine reduced the apparent affinity of the NMDA receptor for glycine (in the presence of spermine) by 10-fold. These results show that taurine interacts directly with the NMDA receptor by multiple mechanisms.

KEYWORDS:

Glycine; NMDA receptor; Prefrontal cortex; Spermine; Taurine; l-type calcium channel

PMID:
24485893
DOI:
10.1016/j.ejphar.2014.01.025
[Indexed for MEDLINE]

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