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-[3H]aspartate uptake. The effect was abolished by an antagonist of kainate/AMPA receptors, CNQX, and mimicked by kainate, but not by AMPA or tACPD. Both glutamate and kainate caused a dramatic up-regulation (82% and 69%, respectively) of GLAST, a predominant glutamate transporter in cultured astroglia, though the mRNA levels appeared unaffected. Long-term treatment of cultures with dBcAMP stimulated D-[3H]aspartate uptake as well as GLAST expression. Apart from glutamate, none of the agonists used was capable of increasing further the uptake capacity of the dBcAMP-treated astroglia. The glutamate receptor-dependent modulation of glutamate transport in astroglial cultures may represent a novel feedback regulatory mechanism for glutamate uptake in the brain.
Gegelashvili
G
G
Department of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen, Denmark.
Civenni
G
G
Racagni
G
G
Danbolt
N C
NC
Schousboe
I
I
Schousboe
A
A
D027322:Amino Acid Transport System X-AG; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis*; D015151:Immunoblotting; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D017470:Receptors, Glutamate / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006023:Glycoproteins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D001224:Aspartic Acid; D003994:Bucladesine