The phospholipase A 2 inhibitor bromophenacyl bromide prevents the depolarization-induced increase in [ 3HAMPA binding in rat brain synaptoneurosomes

Abstract

We previously demonstrated that potassium (KCl)-induced depolarization of synaptoneurosomes prepared from rat telencephalon increased [ 3Hamino-3-hydroxy-5-methylisoxazole-4-propionate ([ 3HAMPA) binding to the AMPA receptor. In the present study, we determined the effects of inhibitors of various calcium-dependent enzymes on this response to depolarization. Treatment of intact synaptoneurosomes with the phospholipase A 2 (PLA 2) inhibitor, bromophenacyl bromide (BPB), produced a marked and dose-dependent reduction in KCl-induced enhancement in [ 3HAMPA binding. BPB had no significant effect on [ 3HTPP accumulation in intact synaptoneurosomes, an index of membrane depolarization. In contrast to BPB, inhibitors of calcium-dependent kinases and proteases did not reduced the KCl-induced increase in [ 3HAMPA binding. The results strengthen the hypothesis that phospholipase-induced modifications of AMPA receptor properties may be an important component of synaptic plasticity.