Abstract
The predominant phospholipase activity present in rat hippocampus is a calcium-independent phospholipase A 2 (302.9 ± 19.8 pmol/mg·min for calcium-independent phospholipase A 2 activity vs. 14.6 ± 1.0 pmol/mg·min for calcium-dependent phospholipase A 2 activity). This calcium-independent phospholipase A 2 is exquisitely sensitive to inhibition by the mechanism-based inhibitor, ( E)-6-(bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2H-pyran -2-one (BEL). Moreover, treatment of hippocampal slices with BEL prior to tetanic stimulation prevents the induction of LTP (40.8 ± 5.6% increase in excitatory postsynaptic potential (EPSP) slope for control slices ( n = 6) vs. 5.8 ± 8.5% increase in EPSP slope for BEL-treated slices ( n = 8)). Importantly, LTP can be induced following mechanism-based inhibition of phospholipase A 2 by providing the end product of the phospholipase A 2 reaction, arachidonic acid, during the application of tetanic stimulation. Furthermore, the induction of LTP after treatment with BEL is dependent on the stereoelectronic configuration of the fatty acid provided since eicosa-5,8,11-trienoic acid, but not eicosa-8,11,14-trienoic acid, rescues LTP after BEL treatment (37.6 ± 16.1% increase in EPSP slope for eicosa-5,8,11-trienoic acid vs. −3.7 ± 5.2% increase in EPSP slope for eicosa-8,11,14-trienoic acid). Collectively, these results provide the first demonstration of the essential role of calcium-independent phospholipase A 2 in synaptic plasticity.
Published Version
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