GLUTAMATE-RECEPTOR AGONISTS UP-REGULATE GLUTAMATE TRANSPORTER GLAST IN ASTROCYTES

LONG-TERM treatment of astrocytes in primary culture with L-glutamate (0.1-3 mM) resulted in a dose-dependent increase in D-[H-3]aspartate u ptake. The effect was abolished by an antagonist of kainate/AMPA recep tors, CNQX, and mimicked by kainate, but not by AMPA or tACPD. Both gl utamate and kainate caused a dramatic up-regulation (82% and 69%, resp ectively) of GLAST, a predominant glutamate transporter in cultured as troglia, though the mRNA levels appeared unaffected. Long-term treatme nt of cultures with dBcAMP stimulated D-[H-3]aspartate uptake as well as GLAST expression. Apart from glutamate, none of the agonists used w as capable of increasing further the uptake capacity of the dBcAMP-tre ated astroglia. The glutamate receptor-dependent modulation of glutama te transport in astroglial cultures may represent a novel feedback reg ulatory mechanism for glutamate uptake in the brain.