ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1460-9568.1998.00008.x
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