Arachidonic acid and lysophosphatidylcholine modulate excitatory transmitter amino acid release from the rat cerebral...

The involvement of phospholipase A2 (PLA2) products in ischemia-evoked release of excitatory neurotransmitter amino acids (EAAs) from the cerebral cortex was studied in a four vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison with untreated animals, arachidonic acid (AA; 5 x 10(-7) M to 5 x 10(-5) M) significantly reduced the ischemia-evoked efflux of glutamate and aspartate into cortical superfusates. Direct application of lysophosphatidylcholine (LysoPC; 55.4 micrograms/ml) to the cerebral cortex of non-ischemic animals resulted in a significant increase in glutamate levels. These results indicate that the immediate products of PLA2 action on plasma membrane phospholipids can either enhance or inhibit excitotoxic amino acid release following cerebral ischemia. The effect of AA is likely to be a result of its ability to inhibit PLA2; that of LysoPC, a consequence of its detergent action.