2nd International Meeting on Metabotropic Glutamate Receptors, 15. - 20.9.1996, Taormina, Sicily-Italy.

Neuropharmacology Vol. 35, No. 6, A77

UPF-523, a class I metabotropic glutamate antagonist, fails to protect hippocampal slices against hypoxic/hypoglycemic injury

Mannaioni, G., Jager, T., Schroder, U.H., Breder, J. , Pellicciari, F., Moroni, F. and Reymann, K.G.


Several mGluR agents reduce the ischemia-induced functional damage in hippocampal slices (Neuroscience, 68, 989; 1995). We investigated whether the inhibition of class 1 metabotropic glutamate receptors (mGluRs) reduces the degree of neuronal injury in rat hippocampal slices.
The slices were transiently exposed (4 min.) to an oxygen- and glucose-free environment in an interface chamber and the synaptically-evoked population spikes in the CA1 region was taken as a measure of neuronal viability. Within one hour after hypoxia/hypoglycemia, the population spikes amplitude recovered to 36.4% of baseline control. Application of the class I mGluR antagonist 1-aminoindan-1,5-dicarboxylic acid (UPF 523) at 10 µM, 30 µM, and 100 µM 20 minutes before until 10 minutes after the event did not reduces neuronal injury, since the recovery rates were only 40.7 %, 46.6 % and 46.8 %, respectively.
Our data suggest that the inhibition of class I mGluRs has neither a beneficial nor a detrimental influence on acute neuronal injury due to hypoxic/hypoglycemic events.
This work was supported by BMBF grant BEO 21-031998B and BIOMED 1 BMH1-CT93-1023 grant.


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