Excitatory amino acid transporters as potential drug targets.
BACKGROUND
Excitatory amino acid transporters (EAATs) are transmembrane proteins responsible for the uptake of (S)-glutamate (Glu) from the synaptic cleft, thereby terminating the glutamatergic neurotransmitter signal. Today five subtypes have been identified. Except for EAAT2, their individual roles or functions in the CNS are yet to be fully understood due to the shortage of subtype-selective ligands.


OBJECTIVE
We examine the latest developments in this field by addressing EAAT expression pattern, localization and pharmacology. We present highlights of published work on inhibitors as well as enhancers which display subtype preference or selectivity and discuss which pathological conditions in the CNS such ligands may be beneficial to.


CONCLUSIONS
Not until subtype-selective enhancers, inhibitors and substrates for all five EAAT subtypes have been discovered can a full and detailed understanding of EAATs be obtained. Thus we encourage collaboration between organic chemists and molecular pharmacologists, who, together, may pave the way for new EAAT ligands of importance.
Bunch
Lennart
L
Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, Department of Medicinal Chemistry, DK-2100 Copenhagen, Denmark. lebu@farma.ku.dk
Erichsen
Mette N
MN
Jensen
Anders A
AA
D002490:Central Nervous System / Q000187:drug effects; D050491:Glutamate Plasma Membrane Transport Proteins / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013569:Synapses / Q000378:metabolism
D050491:Glutamate Plasma Membrane Transport Proteins; D008024:Ligands