SYNERGISTIC POTENTIATION OF GLUTAMATE RELEASE BY ARACHIDONIC-ACID ANDOLEOYL-ACETYL-GLYCEROL

Both the activation of protein kinase C (PKC) and the facilitation of depolarization-evoked glutamate release have been implicated in the in duction of hippocampal long-term synaptic potentiation. These observat ions may be functionally related, since stimulation of PKC activity en hances evoked glutamate release. Recently, it was shown that arachidon ic acid and the diacylglycerol analog oleoyl-acetyl-glycerol activate brain PKC in a synergistic fashion. We report the facilitation of depo larization-induced glutamate efflux from hippocampal mossy fiber synap tosomes due to a combination of arachidonic acid and oleoyl-acetyl-gly cerol. The potentiating effects appeared to depend on the activation o f PKC since they were attenuated by staurosporine. In addition. the ef fects of arachidonic acid and oleoyl-acetyl-glycerol appeared to be li mited to calcium-dependent processes.