N-METHYL-D-ASPARTATE-SENSITIVE GLUTAMATE RECEPTORS INDUCE CALCIUM-MEDIATED ARACHIDONIC-ACID RELEASE IN PRIMARY CULTURES OF CEREBELLAR GRANULE CELLS

Abstract: In primary cultures of cerebellar granule cells, glutamate, aspartate, and N‐methyl‐d‐aspartate (NMDA) induced a dose‐dependent release of [3H]arachidonic acid ([3H]AA) which was selective for these agonists and was inhibited by NMDA receptor antagonists. The agonist‐induced [3H]AA release was reduced by quinacrine at concentrations that inhibited phospholipase A2 (PLA2) 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 PLA2 rather than to the action of PLC followed by diacylglycerol lipase. The receptor‐mediated [3H]AA release was dependent on the presence of extracellular Ca2+ and was mimicked by the Ca2+ ionophore ionomycin. Pretreatment of granule cells with either pertussis or cholera toxin failed to inhibit the receptor‐mediated [3H]AA release. Hence, in cerebellar granule cells, the stimulation of NMDA‐sensitive glutamate receptors leads to the activation of PLA2 that is mediated by Ca2+ ions entering through the cationic channels functioning as effectors of NMDA receptors. A coupling through a toxin‐sensitive GTP‐binding protein can be excluded. Copyright © 1990, Wiley Blackwell. All rights reserved