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Beyond the role of glutamate as a neurotransmitter

Abstract

Glutamate is the principal excitatory neurotransmitter of the central nervous system, but many studies have expanded its functional repertoire by showing that glutamate receptors are present in a variety of non-excitable cells. How does glutamate receptor activation modulate their activity? Do non-excitable cells release glutamate, and, if so, how? These questions remain enigmatic. Here, we review the current knowledge on glutamatergic signalling in non-neuronal cells, with a special emphasis on astrocytes.

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Figure 1: Glutamate is a key metabolite.
Figure 2: Compartmentalization of brain glutamate.
Figure 3: Cytosolic glutamate as a potential transmitter pool.
Figure 4: Immunohistochemical detection of glutamate transporters and receptors in peripheral tissue.

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Acknowledgements

This work was supported, in part, by NIEDH-NIH grants to M.N. We thank A. Cooper, G. M. Knudsen, G. Dienel and A. Schouboe for useful comments, X. Wang for the immunohistochemical analysis of glutamate receptor expression, and J. Rothstein for glutamate transporter antibodies.

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Correspondence to Maiken Nedergaard.

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DATABASES

LocusLink

EAAT1

EAAT2

EAAT3

EAAT4

EAAT5

GluR1–4

GluR5–7

glutamate dehydrogenase

glutamine synthetase

mGluR2

mGluR3

mGluR5

NR1

NR2A

NR2B

NR3A

NR3B

OMIM

multiple sclerosis

FURTHER INFORMATION

Encyclopedia of Life Sciences

amino acid transporters

AMPA receptors

astrocytes and brain signalling

glutamate as a neurotransmitter

metabotropic glutamate receptors

NMDA receptors

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Nedergaard, M., Takano, T. & Hansen, A. Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 3, 748–755 (2002). https://doi.org/10.1038/nrn916

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  • DOI: https://doi.org/10.1038/nrn916

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