Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism.

Published

Journal Article

Slices of hippocampal area CA1 were used to test inhibitors of arachidonic acid metabolism for their effects on glutamate/aspartate release from the CA3-derived Schaffer collateral, commissural, and ipsilateral associational terminals. Test compounds [3 microM nordihydroguaiaretic acid (NDGA) and 1 microM 3-[3-(4-chlorobenzyl)-3-tert-butylthio-5- isopropylindol-2-yl]-2,2-dimethyl-propanoic acid (MK-886)] that reduced the production and release of 5-lipoxygenase metabolites also selectively reduced the K(+)-evoked release of aspartate. In contrast, the cyclooxygenase inhibitor indomethacin (100 microM) selectively enhanced the release of glutamate. At a concentration (100 microM) that nonselectively depressed the release of arachidonic acid and its metabolites, NDGA markedly depressed the release of aspartate, glutamate, and GABA. An inhibitor of the 12-lipoxygenase and an inhibitor of nitric oxide synthase did not affect the K(+)-evoked release of any transmitter amino acid. These results suggest that a 5-lipoxygenase product selectively enhances aspartate release and a cyclooxygenase product selectively depresses glutamate release. They are also consistent with previous evidence that arachidonic acid and/or platelet-activating factor enhances the release and depresses the uptake of glutamate and aspartate. The K(+)-evoked release of excitatory amino acids is much more sensitive to modulation by lipid mediators than is GABA release. Activation of NMDA receptors may enhance the K(+)-evoked release of glutamate and aspartate from CA1 slices by stimulating the production and release of lipid modulators.

Full Text

Duke Authors

Cited Authors

  • Peterson, CL; Thompson, MA; Martin, D; Nadler, JV

Published Date

  • March 1995

Published In

Volume / Issue

  • 64 / 3

Start / End Page

  • 1152 - 1160

PubMed ID

  • 7861146

Pubmed Central ID

  • 7861146

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.1995.64031152.x

Language

  • eng

Conference Location

  • England