N-methyl-D-aspartate releases excitatory amino acids in rat corpus striatum in vivo.
There is a considerable amount of conflicting evidence from several studies as to the action of applied N-methyl-D-aspartate (NMDA) on the release of glutamate and aspartate in the brain. In the present study the effect of NMDA on extracellular levels of endogenous amino acids was investigated in conscious, unrestrained rats using intracerebral microdialysis. NMDA caused dose-related increases in extracellular levels of glutamate and aspartate; threonine and glutamine were unaffected. The NMDA-evoked release of glutamate and aspartate was significantly decreased by the specific NMDA receptor antagonist 3-[(+-)-2-carboxypiperazin-4-yl]-propyl-l-phosphonic acid. In addition, increasing the perfusate concentration (and therefore the extracellular concentration) of Ca2+ significantly enhanced the NMDA-evoked release of glutamate and aspartate, whereas removal of Ca2+ and addition of a high Mg2+ concentration to the perfusate caused a significant reduction in their NMDA-evoked release. Moreover, the NMDA-evoked release of glutamate and aspartate was reduced in decorticate animals. These results demonstrate that, in the striatum in vivo, NMDA causes selective release of endogenous glutamate and aspartate from neurone terminals and that this action occurs through an NMDA receptor-mediated mechanism. The ability of NMDA receptor activation to induce release of glutamate and aspartate, perhaps by a positive feedback mechanism, may be relevant to the pathologies underlying epilepsy and ischaemic and hypoglycaemic brain damage.
Young
A M
AM
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, England.
Bradford
H F
HF
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis; D005110:Extracellular Space / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009994:Osmolar Concentration; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000596:Amino Acids; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008274:Magnesium; D002118:Calcium