Premium
Role of endothelins as mediators of injury‐induced alterations of glial glutamate turnover
Author(s) -
Lehmann Claudia,
Eisner Friederike,
Engele Jürgen
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21512
Subject(s) - glutamate receptor , endothelins , glutaminase , astrocyte , glutamine synthetase , excitotoxicity , biology , extracellular , microbiology and biotechnology , glutamine , biochemistry , neuroscience , central nervous system , receptor , endothelin 1 , amino acid
Abstract Astroglia terminate glutamatergic neurotransmission and prevent excitotoxic extracellular glutamate concentration by clearing synaptically released glutamate through the high‐affinity, sodium‐dependent glutamate transporters GLT‐1 and GLAST. Many brain injures are associated with the disturbed expression of glial glutamate transporters and a subsequent increase of extracellular glutamate to neurotoxic levels. We have now followed up initial hints pointing to endothelins, a family of injury‐regulated peptides, as mediators of this injury‐induced loss of glial glutamate transporter expression. We observed that, in line with such a role, endothelins not only act as potent inhibitors of basal and exogenously (dbcAMP)‐induced expression of GLT‐1 in cortical astrocytes as shown before, but likewise inhibit expression of GLT‐1 or GLAST in astrocytes cultured from the diencephalon, mesencephalon, cerebellum, and spinal cord. We further demonstrate that endothelins equally inhibit GLT‐1 expression in cortical slice cultures, a culture system closely resembling the in vivo situation. Although brain injuries are usually associated with an increase in the expression of the glutamate‐converting enzyme glutamine synthetase, cultured cortical astrocytes maintained with endothelins showed an almost complete loss of glutamine synthetase. Interestingly, the inhibitory effects of endothelins on the expression of glutamine synthetase, but not of glutamate transporters, was overridden by high extracellular glutamate, indicating that the primarily inhibitory action of endothelins on the various components of glial glutamate turnover dissociates in the injured brain. © 2007 Wiley‐Liss, Inc.