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N ‐methyl‐D‐aspartate‐evoked release of cyclo‐oxygenase products in rabbit hippocampus: An in vivo microdialysis study
Author(s) -
Łazarewicz J. W.,
Salińska E.
Publication year - 1995
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490400511
Subject(s) - microdialysis , nmda receptor , prostacyclin , chemistry , thromboxane , stimulation , in vivo , eicosanoid , prostaglandin , thromboxane a synthase , cyclooxygenase , thromboxane a2 , pharmacology , endocrinology , medicine , receptor , biochemistry , arachidonic acid , biology , enzyme , extracellular , platelet , microbiology and biotechnology
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 B 2 (Tx B 2 )‐ and 6‐keto prostaglandin F 1α (6‐keto PGF 1α )‐immunoreactive materials that are stable metabolites of biologically active thromboxane A 2 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 PGF 1α concentrations, respectively. An increase in NMDA concentration to 2.5 mM did not potentiate a peak eicosanoid release, but significantly prolonged this effect. Either 10μM MK‐801 or the extrusion of Ca 2+ from the dialysis medium inhibited the release by about 50%. Quinacrine, a phospholipase A 2 inhibitor (250 μM), decreased the NMDA‐evoked eicosanoid release by 30%, whereas 10μM 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 PGFμ 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. © 1995 Wiley‐Liss, Inc.