INVOLVEMENT OF GLUTAMATE RECEPTOR SUBTYPES IN L-[H-3]NORADRENALINE RELEASE FROM CEREBRAL CORTICAL AND HIPPOCAMPAL SLICES OF MICE

The effects of glutamate receptor agonists and antagonists on l-[3H]noradrenaline (NA) release were examined in cerebral cortical and hippocampal slices of mice by superfusion methods. N-Methyl-d-aspartate (NMDA) at 100 μM significantly stimulated l-[3H]NA release. The NMDA-induced l-[3H]NA release was inhibited by Mg2+ in a concentration-dependent manner. APV (100 μM), phencyclidine (PCP, 10 μM) and MK-801 (10 μM) caused a significant inhibition in the NMDA (100 μM)-induced l-[3H]NA release, but (+)3-PPP did not. Enhancement by NMDA of a high K+-evoked l-[3H]NA release was suppressed by APV (200 μM), PCP (1 μM) and MK-801 (1 μM). In contrast, quisqualate (QA, 10 and 100 μM) and kainate (KA, 10 and 100 μM) stimulated the release in the presence of Mg2+. QA-induced release was inhibited by the toxin of Nephila maculata (1 μM), a Papua New Guinean spider (NSTX), and l-glutamic acid diethyl ester (100 and 500 μM). NMDA, QA and KA did not affect the l-[3H]NA uptake into brain slices, but (+)3-PPP, PCP and MK-801 inhibited the uptake with the order of inhibitory potency of PCP > (+)3-PPP ≫ MK-801. It is suggested that the NMDA receptor channel complex evokes NA release and enhances a depolarization-induced NA release without the regulation of the uptake. Opiate sigma (σ)-receptors, however, may be involved in the uptake of NA. © 1990.