Involvement of glutamate receptor subtypes in l-[(3)H]noradrenaline release from cerebral cortical and hippocampal slices of mice.
The effects of glutamate receptor agonists and antagonists on l-[(3)H]noradrenaline (NA) release were examined in cerebral cortical and hippocampal slices of mice by superfusion methods. N- Methyl- d -aspartate (NMDA) at 100 ?M significantly stimulated l-[(3)H]NA release. The NMDA-induced l-[(3)H]NA release was inhibited by Mg(2+) in a concentration-dependent manner. APV (100 ?M), phencyclidine (PCP, 10 ?M) and MK-801 (10 ?M) caused a significant inhibition in the NMDA (100 ?M)-induced l-[(3)H]NA release, but (+)3-PPP did not. Enhancement by NMDA of a high K(+)-evoked l-[(3)H]NA release was suppressed by APV (200 ?M), PCP (1 ?M) and MK-801 (1 ?M). In contrast, quisqualate (QA, 10 and 100 ?M) and kainate (KA, 10 and 100 ?M) stimulated the release in the presence of Mg(2+). QA-induced release was inhibited by the toxin of Nephila maculata (1 ?M), a Papua New Guinean spider (NSTX), and l-glutamic acid diethyl ester (100 and 500 ?M). NMDA, QA and KA did not affect the l-[(3)H]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 (?)-receptors, however, may be involved in the uptake of NA.
Zhao
X H
XH
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060, Japan.
Kitamura
Y
Y
Nomura
Y
Y