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

Neuropharmacology Vol. 35, No. 6, A97

Protein kinase C is involved in the protective effect of class I metabotropic glutamate receptor agonists against hypoxic/hypoglycemic injury in hippocampal slices

Reymann, K.G., Schroder, U.H., Jager, T., Opitz, T., Sabelhaus, C.F. and Breder, J.

To investigate the influence of metabotropic glutamate receptors (mGluRs) on neuronal injury caused by cerebral hypoxia/ischemia, we employed an in vitro model of hypoxia/hypoglycemia.
Hippocampal slices were transiently exposed to an oxygen and glucose free environment which causes a pronounced drop of both ATP and creatine phosphate, an anoxic depolarization, and an incomplete recovery of synaptically evoked population spikes in the CA1 region after one hour (40.8 ± 3.8% of baseline values). This recovery was used as a measure of neuronal viability. In this model, we applied different agonists specific for class I mGluRs. The agonists trans azetidine-2,4 dicarboxylic acid ( t ADA) and 3,5 dihydroxy-phenylglycine (DHPG) appeared to be highly protective, but only when applied before hypoxia/hypoglycemia. The nonspecific protein kinase inhibitor staurosporine and the highly selective protein kinase C inhibitor chelerythrine attenuated the protective effect of the class I mGluR agonists.
In conclusion we suggest that the activation of the phospholipase C pathway prior to hypoxia/hypoglycemia exhibits a pronounced protective effect which depends on the activation of protein kinase C.

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