"Desensitization" of excitatory amino acid responses in the rat olfactory cortex.

Repeated application of the excitatory amino acid transmitter candidates, L-aspartate and L-glutamate and of N-methyl-D-aspartate, kainate and quisqualate to slices of olfactory cortex evoked progressively smaller depolarizations. These "desensitizations" were concentration-dependent, essentially irreversible and non-selective, although responses to gamma-aminobutyric acid (GABA) and to potassium ions were not significantly depressed. The specific N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, partially blocked the reduction in responses to amino acids which accompanied "desensitization" by N-methyl-D-aspartate, suggesting that activation of receptors is an obligatory step in provoking the phenomenon. "Desensitization" of responses was not prevented by the lectin concanavalin A but was potentiated by ouabain, an inhibitor of the sodium-potassium pump. It is proposed that the phenomenon does not reflect a true desensitization of receptors but is possibly the result of accumulation of intracellular sodium because of overloading the sodium pump. Under circumstances where responses to N-methyl-D-aspartate, quisqualate and kainate were "desensitized" by approx. 96%, depolarizations evoked by L-aspartate and L-glutamate were reduced by only 55%: these residual responses were not antagonized by the excitatory amino acid receptor blockers, (+/-)cis-2,3-piperidine dicarboxylate and 2-amino-4-phosphonobutyrate or by dihydrokainate, an inhibitor of the uptake of glutamate and aspartate. One possibility is that the residual responses reflect an interaction between L-aspartate and L-glutamate and an as yet unknown category of receptors.