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N ‐Methyl‐d‐Aspartate‐Sensitive Glutamate Receptors Induce Calcium‐Mediated Arachidonic Acid Release in Primary Cultures of Cerebellar Granule Cells
Author(s) -
Lazarewicz J. W.,
Wroblewski J. T.,
Costa E.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb05771.x
Subject(s) - nmda receptor , glutamate receptor , pertussis toxin , metabotropic glutamate receptor , receptor , biochemistry , metabotropic receptor , chemistry , biology , g protein
In primary cultures of cerebellar granule cells, glutamate, aspartate, and N ‐methyl‐d‐aspartate (NMDA) induced a dose‐dependent release of [ 3 H]arachidonic acid ([ 3 H]AA) which was selective for these agonists and was inhibited by NMDA receptor antagonists. The agonist‐induced [ 3 H]AA release was reduced by quinacrine at concentrations that inhibited phospholipase A 2 (PLA 2 ) but affected neither the activity of phospholipase C (PLC) nor the hydrolysis of phosphoinositides induced by glutamate or quisqualate. Thus, the increased formation of AA was due to the receptor‐mediated activation of PLA 2 rather than to the action of PLC followed by diacylglycerol lipase. The receptor‐mediated [ 3 H]AA release was dependent on the presence of extracellular Ca 2+ and was mimicked by the Ca 2+ ionophore ionomycin. Pretreatment of granule cells with either pertussis or cholera toxin failed to inhibit the receptor‐mediated [ 3 H]AA release. Hence, in cerebellar granule cells, the stimulation of NMDA‐sensitive glutamate receptors leads to the activation of PLA 2 that is mediated by Ca 2+ ions entering through the cationic channels functioning as effectors of NMDA receptors. A coupling through a toxin‐sensitive GTP‐binding protein can be excluded.