ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Molecular cloning has revealed the existence of at least eight subtypes of metabotropic glutamate receptors (mGluRs). We examined the effect of (2S, 1′R, 2′R, 3′R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV), a selective agonist of the mGluR 2/3 subtype, on excitotoxicity in mouse cortical cell cultures. Addition of DCG-IV to the exposure medium partially attenuated the rapidly triggered excitotoxic death induced by a 5 min exposure to 200 μM NMDA. This neuroprotective effect was reversed by coapplication of α-methyl-4-carboxyphenylglycine (MCPG), an antagonist of mGluRs, by pertussis toxin pretreatment and also by preincubation with dibutyryl cAMP, a stable analogue of cAMP. These results suggest that the activation of mGluR 2/3 is neuroprotective in our system. However, DCG-IV did not attenuate the slowly triggered neuronal death induced by 24 h exposure to low concentrations of NMDA, α-amino-1, 3-cyclopentanedicarboxylic acid (AMPA) or kainate. The failure of DCG-IV to block slowly triggered NMDA neurotoxicity is likely due to weak NMDA agonist activity, as demonstrated in whole-cell recording.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1460-9568.1996.tb01174.x
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