Glutamate-evoked release of arachidonic acid from mouse brain astrocytes.
Brain astrocytes in primary culture from the rat or the mouse have been shown to possess ionotropic and metabotropic glutamatergic receptors. The activation of both types of receptors is responsible for a rise in the cytosolic concentration of calcium, while the stimulation of metabotropic receptors induces the accumulation of inositol phosphates. In the present study, it is demonstrated that in striatal astrocytes from mouse embryos, glutamate evokes a release of arachidonic acid. The nonionotropic receptors involved in this effect appeared to be pharmacologically distinct from those coupled to phospholipase C: (1) glutamate displayed different dose-response curves for the production of inositol phosphates (biphasic: EC50 = 25 and 300 microM) and the release of arachidonic acid (monophasic: EC50 = 200 microM); (2) L(+)-2-amino-4-phosphonobutyric acid (AP4) only antagonized the glutamate-evoked release of arachidonic acid without altering the production of inositol phosphates; (3) when used at a concentration of 0.1 mM, quisqualate induced a higher formation of inositol phosphates than glutamate (2 mM) while, in contrast to glutamate, it only weakly stimulated arachidonic acid release when used either at 0.1 mM or 1 mM. L(+)-2-amino-3-phosphonopropionic acid (AP3) suppressed both responses. The glutamate-evoked release of arachidonic acid seems to be oppositely regulated by protein kinases A and C. Indeed, the stimulation of adenylate cyclase by the beta-adrenergic agonist isoproterenol, vasoactive intestinal peptide, or pretreatment of striatal astrocytes with cholera toxin decreased the glutamate-evoked release of arachidonic acid. In contrast, ATP, which markedly stimulated inositol phosphate production, strongly potentiated the glutamate-evoked release of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Stella
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Laboratoire de Neuropharmacologie, INSERM U114, Collège de France, Paris.
Tencé
M
M
Glowinski
J
J
Prémont
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism; D007051:Ibotenic Acid / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D009928:Organ Specificity; D016318:Quisqualic Acid / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D005971:Glutamates; D007295:Inositol Phosphates; D009498:Neurotoxins; D017470:Receptors, Glutamate; D003515:Cycloleucine; D014316:Tritium; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D016718:Arachidonic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid