Evidence for a direct action of N-methylaspartate on non-neuronal cells.
The effects of N-methylaspartate (NMA) on extracellular amino acids and purine catabolites in the hippocampus were studied with brain dialysis in rats with unilateral hippocampal NMA lesions. In the lesioned side, an increased basal output of glutamine was observed while glutamate was significantly decreased. NMA evoked a drop in extracellular glutamine. The effect was not observed in the lesioned hippocampus. NMA markedly enhanced the release of taurine and phosphoethanolamine (PEA). This response was unchanged in NMA-lesioned hippocampus. Analysis of the tissue content of endogenous amino acids revealed decrements in glutamate and GABA whereas other amino acids were not significantly altered. The resting and NMA-stimulated efflux of inosine was higher in the intact hippocampus. However, the extracellular concentrations of the inosine break-down products hypoxanthine and xanthine were not influenced by a prior NMA lesion, neither before nor after NMA administration. The present findings indicate that NMA releases amino acids (mainly taurine and PEA) from non-neuronal cells. The depression of extracellular glutamine elicited by NMA is probably a neuronal event. A direct stimulation of the energy metabolism of non-neuronal cells by NMA appears to exist as measured by the efflux of purine catabolites. I propose that non-neuronal cells, possibly glia, possess NMA receptors which, upon stimulation, initiate biochemical changes. The physiological significance of these responses remains to be elucidated.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003956:Dialysis; D004983:Ethanolamines / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism
D000596:Amino Acids; D004983:Ethanolamines; D005971:Glutamates; D011687:Purines; D005973:Glutamine; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; C005448:phosphorylethanolamine