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

✍ Scribed by J. W. Łazarewicz; E. Salińska

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 711 KB
• Volume: 40
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490400511

✦ Synopsis

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