Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux.
Astrocyte-enriched cultures prepared from the neonatal rat cortex were prelabelled with either [3H]myoinositol or 45Ca2+ and then exposed to various excitatory amino acids. This resulted in an increase in both the breakdown of membrane inositol phospholipids and Ca2+ flux with the following rank order of efficacy: quisqualate greater than or equal to glutamate (Glu) greater than kainate much greater than N-methyl-D-aspartate. Experiments performed with the Ca2+ ionophore A23187 and in the absence of medium Ca2+ suggested that Glu-evoked 45Ca2+ efflux was primarily the result of an increased influx of extracellular Ca2+. However, Glu-stimulated inositol lipid metabolism was found to be only partially dependent on extracellular Ca2+. The quisqualate-preferring receptor antagonist gamma-glutamylaminomethylsulphonic acid was found to be effective in reversing both Glu-evoked inositol lipid breakdown and Ca2+ flux. The results presented are suggestive of some form of interaction between Glu receptors coupled to inositol lipid turnover and Ca2+ channel opening in astrocytes.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005971:Glutamates / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*
D000596:Amino Acids; D005971:Glutamates; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D005973:Glutamine; D000001:Calcimycin; C042626:gamma-glutamylaminomethylsulfonic acid; D002118:Calcium