THE STRUCTURAL SPECIFICITY OF THE HIGH AFFINITY UPTAKE OF <scp>l</scp>‐GLUTAMATE AND <scp>l</scp>‐ASPARTATE BY RAT BRAIN SLICES

TLDR

The high‑affinity uptake system for l‑glutamate and l‑aspartate in rat cortex may not be specific, as several structurally related acidic amino acids competitively inhibit its activity. The study aimed to investigate whether these four acidic amino acids could act as substrates and play a synaptic role similar to l‑glutamate. Results showed that the uptake is sodium‑dependent but less sensitive to sodium changes and certain drugs than GABA uptake, is broadly inhibited by mercurials and electron‑transport inhibitors, and that the inhibitory amino acids should be considered possible substrates for the transport system.

Abstract

Abstract— The high affinity uptake system for l ‐glutamate and l ‐aspartate in rat cerebral cortex may not be specific for these likely excitatory synaptic transmitters, as threo‐3‐hydroxy‐ dl ‐aspartate, l ‐cysteinesulphinate, l ‐cysteate and d ‐aspartate strongly inhibit the observed high affinity uptake of l ‐[ 3 H]glutamate by rat brain slices in a manner consistent with linear competitive inhibition. These substances should therefore be considered as possible substrates for the transport system. Each of these four acidic amino acids excites central neurones in a manner similar to excitation induced by l ‐glutamate, and as each might occur in brain tissue, their possible synaptic role should be investigated. l ‐Glutamate high affinity uptake was shown to be sodium‐dependent, but under certain conditions appeared to be less sensitive than GABA uptake to changes in the external sodium ion concentration, and to drugs which modify sodium ion movements. This may be relevant to the efficiency of the glutamate uptake process during synaptic depolarization induced by glutamate. l ‐Glutamate high affinity uptake was inhibited in a relatively nonspecific manner by a variety of drugs including mercurials and some electron transport inhibitors.