Release of endogenous and newly synthesized glutamate and of other amino acids induced by non-N-methyl-D-aspartate receptor activation in cerebellar granule cell cultures.

Article date: 1991/1/1

PubMed ID: 1670952

Journal name: Journal of neurochemistry (ISSN: 0022-3042)


Amino acid release studies were performed by an HPLC procedure using differentiated rat cerebellar granule cell cultures. Kainic acid (KA; 50 microM) caused an increase (about threefold) in the release of endogenous glutamate and a lesser, but statistically significant, increase in the release of glutamine, glycine, threonine, taurine, and alanine. Quisqualic acid (QA) and, to a lesser degree, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (both 50 microM) enhanced the release of the following amino acids in the order glutamate greater than aspartate greater than or equal to taurine, whereas the release of other amino acids was either unaffected or affected in a statistically nonsignificant way. The release of glutamate induced by KA was partially (43%) Ca2+ dependent. The other release-inducing effects of KA and QA were not Ca2+ dependent. In all cases, the evoked release could be prevented by the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 6-cyano-2,3-hydroxy-7-nitroquinoxaline, and thus appeared to be receptor mediated. NMDA (5 and 50 microM) had no release-inducing activity. The KA-, QA-, and AMPA-evoked release of newly synthesized [3H]glutamate and [3H]aspartate (formed in the cells exposed to [3H]glutamine) was very similar to the evoked release of endogenous glutamate and aspartate. On the other hand, the release of preloaded D-[3H]aspartate (purified by HPLC in the various fractions analyzed, before radioactivity determination) induced by 50 microM KA was twice as high as that of endogenous glutamate. In the case of high [K+] depolarization, in contrast, the release of preloaded D-[3H]aspartate was approximately 30% lower than that of endogenous glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List: Levi G, Patrizio M, Gallo V

Publication Types: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Amino Acids; Glutamates; Quinoxalines; Receptors, N-Methyl-D-Aspartate; Taurine; Ibotenic Acid; Aspartic Acid; Glutamic Acid; 6-Cyano-7-nitroquinoxaline-2,3-dione; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Quisqualic Acid; Potassium; Kainic Acid; Calcium;

Mesh terms: 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids/metabolism; Animals; Aspartic Acid/metabolism; Calcium/pharmacology; Cells, Cultured; Cerebellum/drug effects; Exocytosis; Glutamates/metabolism; Glutamic Acid; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; Potassium/pharmacology; Quinoxalines/pharmacology; Quisqualic Acid/pharmacology; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate/metabolism; Taurine/metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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