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

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 Ca2+ channel. Taurine did not alter specific [3H] MK-801 binding to rat cortical membranes in the presence of glycine or glutamate; but inhibited spermine-potentiated specific [3H] 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.