Bidirectional modulation of AMPA receptor properties by exogenous phospholipase A2 in the hippocampus

Hippocampus
C ChabotG Massicotte

Abstract

The synaptic modifications underlying long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission in various brain structures may result from changes in the properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. In the present study, we report that treatment of rat synaptoneurosomes with increasing concentrations of phospholipase A2 (PLA2) produces a biphasic effect on AMPA receptor binding, with low concentrations causing a decrease and high concentrations an increase in agonist binding. Analysis of the saturation kinetics of 3H-AMPA binding revealed that the biphasic effect of PLA2 was due to modifications in receptor affinity and not to changes in the maximum number of binding sites for AMPA receptors. The 12-lipoxygenase inhibitors preferentially reduced PLA2-induced decrease in AMPA binding and treatment of hippocampal synaptoneurosomes with arachidonic acid (AA) or 12-HPETE, the first metabolite generated from the hydrolysis of AA by 12-lipoxygenases, decreased 3H-AMPA binding. Moreover, electrophysiological experiments indicated that the 12-lipoxygenase inhibitor baicalein totally blocked LTD formation in area CA1 of hippocampal slices. The ...Continue Reading

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Citations

Oct 27, 2006·Journal of Neural Transmission·E L Schaeffer, W F Gattaz
Aug 31, 2001·Progress in Neurobiology·N Kemp, Z I Bashir
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Aug 25, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Robert J VandenbergAnn D Mitrovic

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