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Glutamate Transporter

L-Glutamate is the predominant excitatory neurotransmitter in the central nervous system and is involved in a wide variety of brain functions, but it is also a key player in the pathogenesis of many neurological disorders. Glutamate transporters play the important role of regulating extracellular glutamate concentrations to maintain dynamic synaptic signaling processes. Stimulation of a glutamatergic neuron will cause release of glutamate into the synapse where it has been estimated that glutamate concentrations will transiently rise to low millimolar concentrations and activate ionotropic and metabotropic glutamate receptors. There are a number of transporter families that transport glutamate and include the plasma membrane excitatory amino acid transporters (EAATs), the vesicular glutamate transporters (VGLUTs), and the glutamate-cysteine exchanger. The EAATs belong to the SLC1 family of transporters that also includes two mammalian neutral amino acid transporters (ASCT1, 2) as well as a large number of prokaryotic neutral and acidic amino acid transporters. Pharmacological inhibitors can be broadly classified into two groups: substrate inhibitors and blockers. A large number of compounds have been identified that manipulate EAAT function, but at present there are very few EAAT-selective compounds that show therapeutic potential for the treatment of neurological disorders.

References

1.Vandenberg RJ, et al. Physiol Rev. 2013;93(4):1621–1657.