Taurine Targets the GluN2b-Containing NMDA Receptor Subtype.

Abstract

As an endogenous neuromodulator in the CNS, Taurine interacts with TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide)-sensitive and TAG-insensitive receptors. Taurine activates the former by opening a Cl− channel and the latter by inhibiting the glutamate NMDA receptor. We sought to resolve the site of taurine’s interaction with the NMDA receptor. We recorded evoked field potential in medial prefrontal cortical slices and compared its dose-dependent inhibition by Ro25-6981, a selective antagonist for the GluN1/GluN2B NMDA receptor sub-type, in the absence or presence of taurine. The result revealed that inhibition of evoked responses mediated by taurine overlapped with that by Ro25-6981, suggesting that taurine modulates NMDA receptor by acting on the NMDA GluN1/GluN2B receptor sub-type. Displacement of specific binding of [3H]spermidine and of [3H]taurine to crude frontal cortical membranes by spermine and spermidine showed that polyamines and taurine may interact at a common binding site, possibly localized at the GluN1 or GluN2B subunit. We also tested for long-term taurine actions on glutamate receptor subunits using western blot determination of NMDA and AMPA receptor subunits expression in synaptosomal membranes prepared from rat frontal cortex following chronic taurine treatment. Thirty daily i.p. injections of taurine (100 mg/kg) significantly increased expression of the NMDA GluN2B, but not GluN1, subunit and decreased expression of the AMPA GluR2 subunit. The up-regulation of the GluN2B subunit suggests its long-term interaction with taurine, and supports its being a major target for taurine action. Down-regulation of the AMPA GluR2 subunit is possibly correlated to an increased recruitment of the GluR2-subunit-lacking, calcium-permeable subtype of AMPA receptor.