ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
N-methyl-D-aspartate (NMDA; 40 μM) induced depolarizations of cortical wedges that were reduced by 30–60% in the presence of D-2-amino-5-phosphonovalerate (D-AP5; 5 μM), ketamine (5 μM), dextrorphan (5 μM), magnesium (500 μM), kynurenate (200 μM), and 1-hydroxy-3-aminopyrrolidone-2 (HA-966; 200 μM). Superfusion with glycine (1 μM-1 mM) did not enhance the action of NMDA in control medium and in media containing D-AP5, ketamine, dextrorphan, or magnesium. In the presence of kynurenate and HA-966, however, NMDA-induced depolarizations were enhanced in a dose-dependent manner by glycine (10 μM-3.16 mM). NMDA antagonism produced by HA-966 appeared to be more completely reversed than that produced by kynurenate. This action of glycine was mimicked by D-serine but not by GABA or L-serine, and was resistant to strychnine (10–50 μM). Reduction of responses to quisqualate by kynurenate was not reversed by glycine.In these cortical wedges, spontaneous synaptic activity was observed in nominally magnesium-free medium and this epileptiform activity could be blocked by the above NMDA antagonists. Glycine and D-serine reversed only the effects of kynurenate and HA-966 on such synaptic activity.These results suggest there is an endogenous glycine-like compound acting on NMDA receptor-ionophore complexes and that displacement of this compound by HA-966 or kynurenate produces antagonism of NMDA.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1460-9568.1989.tb00788.x
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