N-methyl-D-aspartate-evoked release of cyclo-oxygenase 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 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.
Lazarewicz
J W
JW
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Salińska
E
E
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000096:biosynthesis
D016194:Receptors, N-Methyl-D-Aspartate; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016202:N-Methylaspartate; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium