The activation of phospholipase A2 and release of arachidonic acid and other lipid mediators at the synapse: The role of platelet-activating factor

N. G. Bazan, C. F. Zorumski, G. D. Clark

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Seizures promote PLA2 activation which is selectively detectable in isolated synaptosomes by an increased free arachidonic acid (AA) and docosahexaenoic acid (DHA) pool size. During long-term potentiation, a role of AA and its oxygenated metabolites has been explored in several laboratories. We have studied another PLA2 product, platelet-activating factor (PAF, 1-O-alkyl-2-acetylglycerophosphocholine) that is also generated during intense synaptic activity such as seizures. We found specific PAF binding sites in both synaptic and intracellular membranes. Using rat postnatal hippocampal synaptic pairs we have shown that PAF specifically increases the release of excitatory neurotransmitter. This effect is elicited through the synaptic binding site since an antagonist selective for this site blocks the PAF-mediated increase in excitatory neurotransmitter release. Although PAF augments evoked excitatory synaptic currents, it does not alter GABA-mediated inhibitory currents. PAF increases the frequency but not the amplitude of spontaneous excitatory synaptic minis. At present it is not known if the phospholipase A2 that accumulates free polyunsaturated fatty acids is the same as the one that gives rise to PAF. This lipid mediator effect on excitatory synaptic transmission may be a critical step in long term potentiation, synaptic plasticity, memory formation and epileptogenesis.

Original languageEnglish
Pages (from-to)421-427
Number of pages7
JournalJournal of Lipid Mediators
Volume6
Issue number1-3
StatePublished - 1992

Keywords

  • arachidonic acid release
  • phospholipase A activation
  • platelet-activating factor

Fingerprint

Dive into the research topics of 'The activation of phospholipase A2 and release of arachidonic acid and other lipid mediators at the synapse: The role of platelet-activating factor'. Together they form a unique fingerprint.

Cite this