Uptake and Release of N‐Methyl‐d‐Aspartate by Rat Brain Slices

Abstract

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 (K_m 3 MM, V_max 0.07 μmol/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. Reloaded 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.