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- W2005883079 abstract "Astrocytes are responsible for the majority of the clearance of extracellular glutamate released during neuronal activity. dl-threo-β-benzyloxyaspartate (TBOA) is extensively used as inhibitor of glutamate transport activity, but suffers from relatively low affinity for the transporter. Here, we characterized the effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), a recently developed inhibitor of the glutamate transporter on mouse cortical astrocytes in primary culture. The glial Na+-glutamate transport system is very efficient and its activation by glutamate causes rapid intracellular Na+ concentration (Na+i) changes that enable real time monitoring of transporter activity. Na+i was monitored by fluorescence microscopy in single astrocytes using the fluorescent Na+-sensitive probe sodium-binding benzofuran isophtalate. When applied alone, TFB-TBOA, at a concentration of 1 μM, caused small alterations of Na+i. TFB-TBOA inhibited the Na+i response evoked by 200 μM glutamate in a concentration-dependent manner with IC50 value of 43 ± 9 nM, as measured on the amplitude of the Na+i response. The maximum inhibition of glutamate-evoked Na+i increase by TFB-TBOA was > 80%, but was only partly reversible. The residual response persisted in the presence of the AMPA/kainate receptor antagonist CNQX. TFB-TBOA also efficiently inhibited Na+i elevations caused by the application of d-aspartate, a transporter substrate that does not activate non-NMDA ionotropic receptors. TFB-TBOA was found not to influence the membrane properties of cultured cortical neurons recorded in whole-cell patch clamp. Thus, TFB-TBOA, with its high potency and its apparent lack of neuronal effects, appears to be one of the most useful pharmacological tools available so far for studying glial glutamate transporters." @default.
- W2005883079 created "2016-06-24" @default.
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- W2005883079 date "2010-02-01" @default.
- W2005883079 modified "2023-10-18" @default.
- W2005883079 title "Inhibitory effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) on the astrocytic sodium responses to glutamate" @default.
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- W2005883079 doi "https://doi.org/10.1016/j.brainres.2009.12.028" @default.
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