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PharmaBiotec Research Center, Department of Biological Sciences,
Royal Danish School of Pharmacy, DK-2100 Copenhagen, Denmark
L-Glutamic acid is a major excitatory neurotransmitter in
the mammalian central nervous system. The termination of the
glutamatergic transmission and the clearance of the excessive,
neurotoxic concentrations of glutamate is ensured by a high affinity
glutamate uptake system. Four homologous types of Na/K-dependent high
affinity glutamate transporters, glutamate/aspartate transporter,
glutamate transporter 1, excitatory amino acid carrier 1, and
excitatory amino acid transporter 4, have recently been cloned and were
assigned to a separate gene family, together with two neutral amino
acid carriers, alanine/serine/cysteine transporter
1/serine/alanine/threonine transporter and adipocyte amino acid
transporter. The genomic organization of these transporters is still
under investigation. Very little is known about the nature of the
factors and molecular mechanisms that regulate developmental, regional,
and cell type-specific expression of the glutamate transporters and
their aberrant functioning in neurodegenerative diseases (e.g.,
amyotrophic lateral sclerosis and Alzheimer's disease). Some
experimental conditions (e.g., ischemia, corticostriatal lesions,
hyperosmolarity, culturing conditions) and several naturally occurring
and synthetic compounds (e.g., glutamate receptor agonists, dopamine,
1- and 
-adrenergic agonists, cAMP, phorbol esters,
arachidonic acid, nitric oxide, oxygen free radicals, amyloid
-peptide, tumor necrosis factor-, glucocorticosteroids,
unidentified neuronal factors) affect the molecular expression and
activity of glutamate transporters. Further elucidation of the
molecular events that link epigenetic signals with transcriptional and
post-transcriptional mechanisms (e.g., alternative splicing,
translation and post-translational modifications) is crucial for the
development of selective pharmacological tools and strategies
interfering with the expression of the individual glutamate
transporters.
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