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.
Bernard
J
J
Université du Québec à Trois-Rivières, Département de Chimie-Biologie, Canada.
Lahsaïni
A
A
Baudry
M
M
Massicotte
G
G
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
D000098:Acetophenones; D011480:Protease Inhibitors; D014316:Tritium; D011189:Potassium Chloride; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D010770:Phosphotransferases; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide