Activation of N-methyl-D-aspartate-sensitive glutamate receptors stimulates arachidonic acid release in primary cultures of cerebellar granule cells

In cultured granule cells prelabeled with [ 3H]arachidonate the activation of excitatory amino acid receptors by various agonists results in a dose-dependent stimulation of [ 3H]arachidonic acid release. Glutamate and aspartate were the most potent agonists, whereas N-methyl-D-aspartate, kainate and quisqualate were less potent. Other neurotransmitter receptor agonists — GABA, baclofen and norepinephrine — were inactive, while carbachol induced only a slight effect. Since the transmitter-mediated release of [ 3H]arachidonate was blocked by phencyclidine, a selective inhibitor of NMDA-sensitive glutamate receptors, it can be inferred that the effects of all other receptor agonists were indirectly mediated via the release of glutamate from granule cells. Aspartate-evoked release was Ca 2+-dependent and was abolished by the glutamate receptor inhibitors: Mg 2+ ions and 2-amino-5-phosphonovalerate. The inhibitors of phospholipase A 2, quinacrine and p-bromophenacyi bromide, decreased the release of [ 3H]arachidonate in a dose-related manner.