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- Title
Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E<sub>2</sub> synthesis and lipid peroxidation afterin vivoactivation ofN-methyl-d-aspartate receptors in rat hippocampus.
- Authors
Pepicelli, Olimpia; Fedele, Ernesto; Berardi, Maria; Raiteri, Maurizio; Levi, Giulio; Greco, Anita; Ajmone-Cat, Maria Antonietta; Minghetti, Luisa
- Abstract
Using intracerebral microdialysis, we reported previously that acutein vivoactivation of NMDA glutamate receptors triggers rapid and transient releases of prostaglandin E2 (PGE2) andF2-isoprostane 15-F2t-IsoP in the hippocampus of freely moving rats. The formation of the two metabolites– produced through cyclo-oxygenase (COX) enzymatic activity and free radical-mediated peroxidation of arachidonic acid (AA), respectively,– was prevented by the specific NMDA antagonist MK-801, and was largely dependent on COX-2 activity. Here, we demonstrate that besides COX-2, which is the prominent COX isoform in the brain and particularly in the hippocampus, the constitutive isoform, COX-1 also contributes to prostaglandin (PG) synthesis and oxidative damage followingin vivoacute activation of hippocampal NMDA glutamate receptors. The relative contribution of the two isoforms is dynamically regulated, as the COX-2 selective inhibitor NS398 immediately prevented PGE2 and 15-F2t-IsoP formation during the application of NMDA, whereas the COX-1 selective inhibitor SC560 was effective only 1 h after agonist infusion. Our data suggest that, although COX-2 is the prominent isoform, COX-1 activity may significantly contribute to excitotoxicity, particularly when considering the amount of lipid peroxidation associated with its catalytic cycle. We suggest that both isoforms should be considered as possible therapeutic targets to prevent brain damage caused by excitotoxicity.
- Subjects
CYCLOOXYGENASES; METHYL aspartate; PROSTAGLANDINS; HIPPOCAMPUS (Brain); NEUROCHEMISTRY
- Publication
Journal of Neurochemistry, 2005, Vol 93, Issue 6, p1561
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2005.03150.x