Uptake and release of N-methyl-D-aspartate by rat brain slices.

The excitant amino acid, N-methyl-D-aspartate, was actively taken up by slices of rat cerebral cortex. This uptake was Na+- and temperature-dependent, but was relatively inefficient (Km 3 mM, Vmax 0.07 mumol/g/min) compared with that of other acidic amino acids. The uptake of N-methyl-D-aspartate does not appear to have a rate-limiting influence on the time course of N-methyl-D-aspartate-induced excitation since potent uptake inhibitors, such as threo-3-hydroxy-L-aspartate, do not influence the excitant action of N-methyl-D-aspartate. The relatively prolonged excitant action of this acidic amino acid may be the result of relatively slow dissociation of the activated receptor complex. Preloaded N-methyl-D-aspartate can be released from rat brain slices by stimulation with K+ ions. Such K+-stimulated release appeared to be Ca2+-independent, unlike the K+-stimulated release of preloaded D-aspartate. These findings suggest that N-methyl-D-aspartate may be a weak but selective substrate for a glial acidic amino acid uptake system.