Stimulation of Inositol Phospholipid Hydrolysis by Excitatory Amino Acids Is Enhanced in Brain Slices from Vulnerable Regions after Transient Global Ischemia

Abstract

Stimulation of inositol phospholipid hydrolysis by transmitter receptor agonists was measured in slices from hippocampus, cerebral cortex, and corpus striatum at various intervals after transient global ischemia in rats. Ischemia was induced through the four-vessel occlusion model. Stimulation of [3H]inositol monophosphate formation by excitatory amino acids was greatly enhanced in hippocampal slices prepared from ischemic rats at 24 h or 7 days after reperfusion. This potentiation was more evident using ibotenic acid and was also observed in cerebral cortex, but not in corpus striatum. This regional profile correlated with the pattern of ischemia-induced neuronal damage observed under our experimental conditions. The enhanced responsiveness to excitatory amino acids was always accompanied by an increase in both basal and norepinephrine-stimulated [3H]inositol monophosphate formation. In contrast, stimulation of [3H]inositol monophosphate formation by carbamylcholine was not modified in hippocampal or cortical slices from ischemic animals.

The Activation of Metabotropic Glutamate Receptors Protects Nerve Cells from Oxidative Stress

“…Therefore, there are different coupling mechanisms between the stress signal transduction pathways and mGluR subtypes in cortical neurons and HT-22 cells. These data indicate, however, that the response to stress is similar and are consistent with in vivo results that show that group I mGluRs are upregulated in the hippocampus after transient global ischemia (Chen et al, 1988;Seren et al, 1989). The expression of mGluR5 is also modified by protein growth factors in cultured cortical astrocytes.…”

Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and -5 on astrocyte proliferation in culture

“…Perhaps one of the functions of mGlu5 receptors is to stimulate astrocyte proliferation during early postnatal life, thus ensuring the proper match between synaptic terminals and neighbour glial cells. It would be interesting to test whether an increased expression of mGlu5 receptors in astrocytes contributes to the upregulation of mGlu receptor-agonist stimulated PI hydrolysis found after brain injury (Nicoletti et al, 1986;Chen et al, 1988;Seren et al, 1989), as a potential mechanism leading to astrocyte proliferation and reactive gliosis.…”

RGS4 Inhibits Signaling by Group I Metabotropic Glutamate Receptors

“…Net transmission through glutamatergic circuits can be impacted dramatically by the mGluRs present at a given synapse, and signaling by mGluRs is dynamically regulated under various physiological and pathological conditions (Akiyama et al, 1987;Seren et al, 1989;Yamada et al, 1989;Aronica et al, 1991;Chen et al, 1992;Mayat et al, 1994). Delineation of the mechanisms involved in regulating mGluR f unction will be critical for development of a complete understanding of regulation of transmission at glutamatergic synapses.…”