Using superfusion with albumin-containing medium of hippocampal and striatal slices of adult and developingrats at postnatal days(PND) 7-10, prelabelled with [3H]arachidonic acid ([3H]AA) we detected N-methyl-D-aspartate (NMDA) evoked release to the superfusion medium of radiolabelld material, 70% of which was associated with arachidonic acid (AA) and its metabolite.[3H[AA release was much more pronounced in PND 7-10 rats than in adults, and the response to NMDA in the hippocampal slices exceed the reactions in the striatal slices.The subsequent experiments, emplyoing only hippocampal slices of PND 7-10 rats, demonstrated that NMDA-stimulated [3H]AA release was dose-depended in the micromolar range,was sensitive to NMDA receptor antagonists, and wasinhibited in calcium-free medium and the presence of quinacrine.[3H]AA release induced by 100 ?M NMDA was not significantly inhibited by magnesium but was completly blocked by 7 Cl-kynurenic acid and ifenprodil (both antagonists 100 ?M).The sulfhydryl reducing reagent dithiothreitol induced [3H]AA release; this response was sensitive to NMDA receptor antagonists.These data indicate that the NMDA induced, calcium triggered, and phospholipides A2 depended AA release is highly pronounced in the developing rat hippocampus.NMDA receptors mediating AA release in the hippocampus of PND 7-10 rats are subject to glycine, polyamine and redox modulationn, but they show low sensitivity to Mg2+ inhibition.
The aim of this in vivo microdialysis study was to characterise the regulation of prostaglandin D2 (PgD2) synthesis by NMDA receptors in the rabbit hippocampus in relation to changes in extracellular Ca2+ concentration ([Ca2+]e) and nitric oxide (NO) levels. Samples of dialysate were analysed for changes in PgD2 concentration, in [Ca2+]e and in the level of NO. The results demonstrated that a 20-min pulse application of 0.1 - 2.5 mM NMDA via a microdialysis probe induced a prolonged stimulation of PgD2 release that was sensitive to competitive NMDA receptor antagonists. An inhibitor of voltage-sensitive Na+ channels, tetrodotoxin, did not influence this effect but significantly suppressed basal PgD2 production, whereas a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), prevented NMDA-evoked NO release and inhibited NMDA-induced PgD2 release in an L-arginine-sensitive manner. NO donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside, stimulated PgD2 release. NMDA-evoked decrease in [Ca2+]e was insensitive to TTX and L-NAME. These results demonstrate an in vivo NMDA receptor-mediated modulation of PgD2 synthesis in the brain, in which NO participates.
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.