Abstract
Ionotropic glutamate receptors are well known to play a major role in neuronal degeneration after cerebral ischemia. However, we are interested in the possible role of metabotropic glutamate receptors (mGluR) during ischemia. The aim of this study was to examine how agonists and antagonists with different affinity for the various mGluR subtypes may influence a hypoxic/hypoglycemic injury in rat hippocampal slices. For this purpose we monitored the electrophysiological recovery of CA1 neurons after a short hypoxic/hypoglycemic period, which was sufficient to abolish the electrophysiological response to test stimuli applied to Schaffer collateral/commissural pathway. Various agonists known to act at different mGluR subtypes were bath applied 20 min before the insult and washed out 10 min after it. In this model, the two mGluR antagonists L-aminophosphonopropionate (L-AP3) and (+)-α-methyl-4-carboxyphenylglycine (MCPG) were able to enhance this recovery significantly. Since the two substances exhibit different effects on forskolin induced cAMP formation, but are both able to antagonize ACPD induced phosphoinositide hydrolysis, we suppose that the blockade of the phospholipase C (PLC) coupled mGluRs could be the reason for the protective effects. The mGluR agonist ACPD, which is known to activate all 6 described mGluR subtypes, also exhibited a clear protective effect on the recovery of evoked field potentials. However, there was no effect of trans-azetidine-2,4-dicarboxylic acid (tADA), an agonist specific to the PLC coupled mGluR. Furthermore, 2S,3S,4S-α-(carboxycyclopropyl)glycine (L-CCG-I), an mGluR agonist with a higher specificity to the PLC coupled class, was not able to enhance the posthypoxic/hypoglycemic recovery. These data suggest that various mGluR subtypes play different roles in hypoxic/hypoglycemic injury.
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Opitz, T., Reymann, K. Metabotropic Glutamate Receptors Are Involved in Hypoxic/Hypoglycemic Injury of Hippocampal CA1 Neurons in vitro. Neuropsychopharmacol 11, 278 (1994). https://doi.org/10.1038/sj.npp.1380186
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DOI: https://doi.org/10.1038/sj.npp.1380186