"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.
Collins
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Surtees
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D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA; D011955:Receptors, Drug / Q000378:metabolism; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism
D000596:Amino Acids; D001224:Aspartic Acid; D003208:Concanavalin A; D005971:Glutamates; D018698:Glutamic Acid; D010042:Ouabain; D018091:Receptors, AMPA; D011955:Receptors, Drug; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter