N‐methyl‐D‐aspartate‐evoked release of cyclo‐oxygenase products in rabbit hippocampus: An in vivo microdialysis study

Abstract

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 B2 (Tx B2)- and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha)-immunoreactive materials that are stable metabolites of biologically active thromboxane A2 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 B2 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 microM MK-801 or the extrusion of Ca2+ from the dialysis medium inhibited the release by about 50%. Quinacrine, a phospholipase A2 inhibitor (250 microM), decreased the NMDA-evoked eicosanoid release by 30%, whereas 10 microM indomethacin, a cyclo-oxygenase inhibitor, completely suppressed the release. One hundred micromolar furegrelate, an inhibitor of thromboxane synthase, reduced by 75% Tx B2 release with concomitant 100% increase in 6-keto PGF1 alpha formation. Thus, stimulation of NMDA receptors induces calcium-dependent formation of thromboxane A2 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.