title: Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism.
abstract: 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.
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: C L
authors.initials: CL
authors.lastname: Peterson
authors.forename: M A
authors.initials: MA
authors.lastname: Thompson
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: J V
authors.initials: JV
authors.lastname: Nadler
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D016718:Arachidonic Acid / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001224:Aspartic Acid / Q000378:metabolism*; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D019323:omega-N-Methylarginine; D002722:Chlorobenzenes
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D016718:Arachidonic Acid; D001120:Arginine; D001224:Aspartic Acid; D044950:Flavanones; D005419:Flavonoids; D005971:Glutamates; D007211:Indoles; D007213:Indomethacin; D009637:Masoprocol; D010972:Platelet Activating Factor; D011188:Potassium; D011451:Prostaglandin-Endoperoxide Synthases; D011796:Quinacrine; D017470:Receptors, Glutamate; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D019323:omega-N-Methylarginine; C060893:MK-886; D002722:Chlorobenzenes; C006680:baicalein