کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4327325 1614123 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibitory effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) on the astrocytic sodium responses to glutamate
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Inhibitory effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) on the astrocytic sodium responses to glutamate
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1316, 26 February 2010, Pages 27–34
نویسندگان
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