Glutamate stimulates 2-deoxyglucose uptake in rat cerebellar granule cells.
Although glutamate is the most widely used excitatory neurotransmitter in mammalian brain a prolonged exposure of neurons to this amino acid causes their degeneration and death, an event also referred to as excitotoxicity. Since one of the earliest events of excitotoxicity is an impairment of energy metabolism, we have assessed whether such damage is due to a concomitant alteration of glucose uptake in rat cerebellar granule cells. We report that glutamate rather than inhibiting actually activates glucose uptake in a time- and temperature-dependent fashion and that this effect is completely blocked by MK-801, a specific inhibitor of glutamate receptors of the NMDA type. Moreover, while the rate of glucose uptake is constant between 2 DIV and 10 DIV, the extent of glutamate-triggered increase above the basal level is undetectable at 2 DIV and becomes progressively higher with days of incubation in cultures, in a fashion overlapping the appearance of functionally active glutamate receptors. The action of this excitatory amino acid is also mimicked, to various extents, by other glutamate agonists such as kainate, NMDA and quisqualate. The glutamate stimulation of glucose uptake occurs in the same range of concentrations as those necessary to cause neuronal death. These findings are discussed in the light of the possible metabolic mechanism responsible of such activation and in connection with previous similar studies performed on glial or mixed glial-neuronal cultures, whereby the stimulating action of glutamate is achieved via alternate pathways not involving glutamate receptors.
Minervini
M
M
Institute of Neurobiology, C.N.R., Rome, Italy.
Atlante
A
A
Gagliardi
S
S
Ciotti
M T
MT
Marra
E
E
Calissano
P
P
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D016318:Quisqualic Acid; D003847:Deoxyglucose; D007608:Kainic Acid