Involvement of Lipid Metabolism in Chemical Transmission Processes at Mossy Fiber Synapses
Abstract
Isolated hippocampal mossy fiber synaptosomes were used to assess the relationships between membrane lipid metabolism and the evoked release of the excitatory amino acid neurotransmitter glutamate. A variety of metabolic parameters were investigated in order to develop a comprehensive model for the mechanisms of transmitter release. Mossy fiber terminals were radiolabeled with 3H arachidonic acid and the effects of membrane depolarization and calcium influx on the labeling of the component lipid pools were determined. It was observed that depolarization and Ca2+ influx stimulated the accumulation of unesterified arachidonate. This effect was correlated with increased production of prostaglandins, in particular PGF2a and could be blocked with lipase inhibitors and Ca2+ channel blockers. Prostaglandin production was also blocked by cyclooxygenase and lipoxygenase inhibitors. We also observed that exogenous arachidonate stimulates the release of endogenous glutamate from mossy fiber terminals, as well as the mobilization of intraterminal free Ca2+. In addition we identified two naturally occurring products which act synergistically to activate protein kinase C and facilitate the evoked release of glutamate.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 24, 1993
- Accession Number
- ADA266250
Entities
People
- Robert V. Dorman
Organizations
- Kent State University