N-methyl-D-aspartate-sensitive glutamate receptors induce calcium-mediated arachidonic acid release in primary cultures of cerebellar granule cells.
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.
Lazarewicz
J W
JW
Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, D.C.
Wroblewski
J T
JT
Costa
E
E
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001224:Aspartic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001095:Arachidonic Acids; D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D001224:Aspartic Acid; D015759:Ionomycin; D016202:N-Methylaspartate; D002772:Cholera Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011796:Quinacrine; D002118:Calcium