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A presynaptic N-methyl-d-aspartate autoreceptor in rat hippocampus modulating amino acid release from a cytoplasmic pool

A possible role of the N‐methyl‐d‐aspartate receptor (NMDA‐R) as a presynaptic autoreceptor was investigated using Percoll‐purified hippocampus nerve terminals (synaptosomes). This preparation contained only a neglectable amount of postsynaptic structures. Two main effects of NMDA were observed. Fir...

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Bibliographic Details
Published in:The European journal of neuroscience 1998-01, Vol.10 (1), p.106-114
Main Authors: Breukel, Alexandra I. M., Besselsen, Elly, Da Silva, Fernando H. Lopes, Ghijsen, Wim E. J. M.
Format: Article
Language:English
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Summary:A possible role of the N‐methyl‐d‐aspartate receptor (NMDA‐R) as a presynaptic autoreceptor was investigated using Percoll‐purified hippocampus nerve terminals (synaptosomes). This preparation contained only a neglectable amount of postsynaptic structures. Two main effects of NMDA were observed. First, NMDA dose‐dependently (10–100 μm) and in the absence of Mg2+, stimulated basal release of aspartate and glutamate, but not of GABA. MK801 (10 μm), an open NMDA‐R‐channel blocker, reduced this effect even below control levels, indicating endogenous NMDA‐R activation. By superfusing synaptosomes, which prevents a tonic receptor occupation, also basal GABA release was stimulated by NMDA. The NMDA‐induced potentiation of amino acid superfusate levels was blocked both by MK801 and Mg2+ (1 m m), was slow in onset and returned to baseline after NMDA‐removal. The NMDA‐effect was also found in the absence of extracellular Ca2+, suggesting that amino acids were released from a non‐vesicular (cytoplasmic) pool. Secondly, in KCl‐depolarized synaptosomes exposed to 1 m m Mg2+, NMDA did not affect the release of the amino acids. MK801, however, reduced the KCl‐evoked Ca2+‐independent release of aspartate and glutamate, but not of GABA. l‐trans‐PDC, the selective inhibitor of the glutamate/aspartate transporter, prevented this MK801‐effect, suggesting a coupling between NMDA‐Rs and these transporters. These data provide evidence for a presynaptic NMDA autoreceptor in rat hippocampus. We speculate on the role of this NMDA‐R to depolarize the presynaptic membrane by Na+‐entry, which may induce reversal of amino acid transporters and thereby releasing amino acids from a cytoplasmic pool.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.1460-9568.1998.00008.x