The phospholipase A2 inhibitor bromophenacyl bromide prevents the depolarization-induced increase in [3H]AMPA binding in rat brain synaptoneurosomes.

We previously demonstrated that potassium (KCl)-induced depolarization of synaptoneurosomes prepared from rat telencephalon increased [3H]amino-3-hydroxy-5-methylisoxazole-4-propionate ([3H]AMPA) 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 A2 (PLA2) inhibitor, bromophenacyl bromide (BPB), produced a marked and dose-dependent reduction in KCl-induced enhancement in [3H]AMPA binding. BPB had no significant effect on [3H]TPP 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 [3H]AMPA binding. The results strengthen the hypothesis that phospholipase-induced modifications of AMPA receptor properties may be an important component of synaptic plasticity.