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Journal of Neuroscience, Vol 14, 568-575, Copyright © 1994 by Society for Neuroscience
Glutamate-evoked release of arachidonic acid from mouse brain astrocytes
N Stella, M Tence, J Glowinski and J Premont
Laboratoire de Neuropharmacologie, INSERM U114, College de France, Paris.
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)
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