Activation of Multiple Metabotropic Glutamate Receptor Subtypes Prevents NMDA‐induced Excitotoxicity in Rat Hippocampal Slices

Activation of Multiple Metabotropic Glutamate Receptor Subtypes Prevents NMDA‐induced... Metabotropic glutamate receptors (mGluRs) belong to a relative large receptor family consisting of multiple members with important roles in a number of brain functions. We report here that activation of mGluRs prevents the neurotoxic effect induced by N‐methyl‐D‐aspartate (NMDA) in slices from the rat hippocampus. Neuroprotection was elicited when slices were simultaneously exposed to both the selective mGluR agonist (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid (tACPD) and NMDA. Persisting stimulation of mGluRs after the toxic exposure did not improve the survival of pyramidal or granular cells. The neuroprotection elicited by tACPD was also evoked by its active isomer, (1 S,3R)‐ACPD, and was prevented by the selective mGluR antagonist (+)‐α‐methyl‐4‐carboxyphenyl‐glycine (500 μM), confirming that mGluR activation is involved in the mechanism of action of tACPD. The effect of 100 μM tACPD was reproduced by 100 μM quisqualate, an agonist for mGluR1 and mGluR5, and by 1 μM of (2S,1's,2's)‐2‐carboxycyclopropyl‐glycine, a preferential agonist of mGluR2 and mGluR3 subtypes. No neuroprotection was induced by L‐2‐amino‐4‐phospnonobutyrate, a selective agonist for mGluR4, mGluR6, mGluR7 and mGluR8, at 500 μM. Since the NMDA‐mediated cell death in hippocampal slices is considered relevant to ischaemia‐induced brain injury, these results indicate that mGluRs may be important safety devices used by neurons to decrease their sensitivity to excitotoxic stimuli and increase their chance of survival. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Activation of Multiple Metabotropic Glutamate Receptor Subtypes Prevents NMDA‐induced Excitotoxicity in Rat Hippocampal Slices

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Publisher
Wiley
Copyright
Copyright © 1996 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
D.O.I.
10.1111/j.1460-9568.1996.tb01614.x
Publisher site
See Article on Publisher Site

Abstract

Metabotropic glutamate receptors (mGluRs) belong to a relative large receptor family consisting of multiple members with important roles in a number of brain functions. We report here that activation of mGluRs prevents the neurotoxic effect induced by N‐methyl‐D‐aspartate (NMDA) in slices from the rat hippocampus. Neuroprotection was elicited when slices were simultaneously exposed to both the selective mGluR agonist (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid (tACPD) and NMDA. Persisting stimulation of mGluRs after the toxic exposure did not improve the survival of pyramidal or granular cells. The neuroprotection elicited by tACPD was also evoked by its active isomer, (1 S,3R)‐ACPD, and was prevented by the selective mGluR antagonist (+)‐α‐methyl‐4‐carboxyphenyl‐glycine (500 μM), confirming that mGluR activation is involved in the mechanism of action of tACPD. The effect of 100 μM tACPD was reproduced by 100 μM quisqualate, an agonist for mGluR1 and mGluR5, and by 1 μM of (2S,1's,2's)‐2‐carboxycyclopropyl‐glycine, a preferential agonist of mGluR2 and mGluR3 subtypes. No neuroprotection was induced by L‐2‐amino‐4‐phospnonobutyrate, a selective agonist for mGluR4, mGluR6, mGluR7 and mGluR8, at 500 μM. Since the NMDA‐mediated cell death in hippocampal slices is considered relevant to ischaemia‐induced brain injury, these results indicate that mGluRs may be important safety devices used by neurons to decrease their sensitivity to excitotoxic stimuli and increase their chance of survival.

Journal

European Journal of NeuroscienceWiley

Published: Jul 1, 1996

References

  • Agonist analysis of 2‐(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells
    Hayashi, Hayashi; Tanabe, Tanabe; Aramori, Aramori; Masu, Masu; Shimamoto, Shimamoto; Ohfune, Ohfune; Nakanishi, Nakanishi
  • Molecular diversity and functions of glutamate receptors
    Nakanishi, Nakanishi; Masu, Masu
  • N ‐methyl‐D‐aspartate neurotoxicity in hippocampal slices: protection by aniracetam
    Pizzi, Pizzi; Consolandi, Consolandi; Memo, Memo; Spano, Spano

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