N-METHYL-D-ASPARTATE-EVOKED RELEASE OF CYCLOOXYGENASE PRODUCTS IN RABBIT HIPPOCAMPUS - AN IN-VIVO MICRODIALYSIS STUDY

In vivo microdialysis of the rabbit hippocampus was used to study the effects of N-methyl-D-aspartate (NMDA) receptor stimulation on dialysate concentrations of thromboxane B-2 (Tx B-2)- and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha)-immunoreactive materials that are stable metabolites of biologically active thromboxane A, and prostacyclin. All pharmacological substances were applied in the dialysis medium, The application of 1 mM NMDA for 20 min resulted in five- and eightfold increases in Tx B-2 and 6-keto PGF1 alpha concentrations, respectively. An increase in NMDA concentration to 2.5 mM did not potentiate a peak eicosanoid release, but significantly prolonged this effect. Either 10 mu M MK-801 or the extrusion of Ca2+ from the dialysis medium inhibited the release by about 50%. Quinacrine, a phospholipase A(2) inhibitor (250 mu M), decreased the NMDA-evoked eicosanoid release by 30%, whereas 10 mu M indomethacin, a cyclo-oxygenase inhibitor, completely suppressed the release. One hundred micromolar furegrelate, an inhibitor of thromboxane synthase, reduced by 75% Tx B-2 release with concomitant 100% increase in 6-keto PGF1 alpha formation. Thus, stimulation of NMDA receptors induces calcium-dependent formation of thromboxane A(2) and prostacyclin in the hippocampus, which may have pathophysiological implications. The neuronal site of their formation seems probable, although a transcellular mechanism of their synthesis should be also considered. (c) 1995 Wiley-Liss, Inc.