Activation of polyphosphoinositide metabolism as a signal-transducing system coupled to excitatory amino acid receptors in astroglial cells.
Excitatory amino acids (EAA) are known to induce an increase in the breakdown of polyphosphoinositides (PI) in brain slices and in dispersed cultures of neurons. We have now used astroglia cultured from newborn rat cerebra to demonstrate that glutamate provokes, in [3H]inositol-labeled cells, an accumulation of inositol phosphates in a time- and concentration-dependent manner. The ED50 value for glutamate was 40 microM. Quisqualate, ibotenate, and kainate were also active, with their relative potencies in the order of quisqualate greater than ibotenate much greater than kainate. No effect was detected with N-methyl-D-aspartate and quinolinic acid in the absence of Mg2+. The nonselective glutamate receptor antagonist gamma-D-glutamylglycine fully inhibited glutamate agonist-induced PI breakdown. A brief pretreatment of the astroglial cells with phorbol esters negated these effects of EAA receptor agonists, suggesting a feedback role for protein kinase C in phospholipase C action. Glutamate also elevated cytosolic free Ca2+ in Fura-2-loaded astroglial cells, as assessed by digital fluorescence imaging microscopy. Since a close metabolic partnership is known to exist between neurons and glia, these findings may have important functional consequences for neural cells in vivo.
Milani
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D
Fidia Research Laboratories, Department of CNS Research, Abano Terme, Italy.
Facci
L
L
Guidolin
D
D
Leon
A
A
Skaper
S D
SD
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D006152:Cyclic GMP / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology / Q000502:physiology*; D018698:Glutamic Acid; D007295:Inositol Phosphates / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects*; D013403:Sugar Phosphates / Q000378:metabolism*
D005971:Glutamates; D007295:Inositol Phosphates; D010069:Oxadiazoles; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D013403:Sugar Phosphates; D018698:Glutamic Acid; D016318:Quisqualic Acid; D006152:Cyclic GMP; D007608:Kainic Acid; D002118:Calcium