Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux

Abstract

Astrocyte-enriched cultures prepared from the neonatal rat cortex were prelabelled with either [ 3H]myoinositol or 45Ca 2+ and then exposed to various excitatory amino acids. This resulted in an increase in both the breakdown of membrane inositol phospholipids and Ca 2+ flux with the following rank order of efficacy: quisqualate≧ glutamate ( Glu)> kainate⪢ N-methyl- d-aspartate . Experiments performed with the Ca 2+ ionophore A23187 and in the absence of medium Ca 2+ suggested that Glu-evoked 45Ca 2+ efflux was primarily the result of an increased influx of extracellular Ca 2+. However, Glu-stimulated inositol lipid metabolism was found to be only partially dependent on extracellular Ca 2+. The quisqualate-preferring receptor antagonist γ-glutamylaminomethylsulphonic acid was found to be effective in reversing both Glu-evoked inositol lipid breakdown and Ca 2+ flux. The results presented are suggestive of some form of interaction between Glu receptors coupled to inositol lipid turnover and Ca 2+ channel opening in astrocytes.