Acute up‐regulation of glutamate uptake mediated by mGluR5a in reactive astrocytes
- 10 June 2005
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 94 (2) , 405-416
- https://doi.org/10.1111/j.1471-4159.2005.03216.x
Abstract
Excitatory transmission in the CNS necessitates the existence of dynamic controls of the glutamate uptake achieved by astrocytes, both in physiological conditions and under pathological circumstances characterized by gliosis. In this context, this study was aimed at evaluating the involvement of group I metabotropic glutamate receptors (mGluR) in the regulation of glutamate transport in a model of rat astrocytes undergoing in vitro activation using a cocktail of growth factors (G5 supplement). The vast majority of the cells were found to take up aspartate, mainly through the glutamate/aspartate transporter (GLAST), and at least 60% expressed functional mGluR5a. When exposed for 15 s to the selective group I mGluR agonist (S)‐3,5‐dihydroxyphenylglycine, reactive astrocytes showed a significant increase in their capacity to take up aspartate. This effect was confirmed at the single‐cell level, since activation of mGluRs significantly increased the initial slope of aspartate‐dependent Na+ entry associated with the activity of glutamate transporters. This up‐regulation was inhibited by an antagonist of mGluR5 and, more importantly, was sensitive to a specific glutamate transporter 1 (GLT‐1) blocker. The acute influence of mGluR5 on aspartate uptake was phospholipase C‐ and protein kinase C‐dependent, and was mimicked by phorbol esters. We conclude that mGluR5a contributes to a dynamic control of GLT‐1 function in activated astrocytes, acting as a glial sensor of the extracellular glutamate concentration in order to acutely regulate the excitatory transmission.Keywords
This publication has 50 references indexed in Scilit:
- Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetiiCellular Microbiology, 2007
- Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type A receptors in glioma cellsBiochimica et Biophysica Acta (BBA) - Biomembranes, 2005
- Molecular and functional characterisation of glutamate transporters in rat cortical astrocytes exposed to a defined combination of growth factors during in vitro differentiationNeurochemistry International, 2004
- Metabotropic glutamate receptor agonists reduce glutamate release from cultured astrocytesGlia, 1999
- Regulation of the glial glutamate transporter GLT‐1 by glutamate and δ‐opioid receptor stimulationFEBS Letters, 1998
- A neurotoxic prion protein fragment enhances proliferation of microglia but not astrocytes in cultureGlia, 1996
- Immunocytochemical characterization of a new marker of fibrous and reactive astrocytesCell and tissue research, 1995
- Effects of growth factors on phosphatidylinositol-3 kinase in astroglial cellsJournal of Neuroscience Research, 1995
- Novel neuron-related regulatory mechanisms for astrocytic glutamate and GABA high affinity uptakeNeuroscience Letters, 1983
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970