N-methyl-D-aspartate autoreceptors respond to low and high agonist concentrations by facilitating, respectively, exocytosis and carrier-mediated release of glutamate in rat hippocampus
✍ Scribed by Elisa Luccini; Veronica Musante; Elisa Neri; Maurizio Raiteri; Anna Pittaluga
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 219 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Presynaptic NMDA autoreceptors regulating glutamate release have rarely been investigated. High‐micromolar N‐methyl‐D‐aspartate (NMDA) was reported to elicit glutamate release from hippocampal synaptosomes in a Ca^2+^‐independent manner by reversal of excitatory amino acid transporters. The aim of this work was to characterize excitatory amino acid release evoked by low‐micromolar NMDA from glutamatergic axon terminals. Purified rat hippocampal synaptosomes were prelabelled with [^3^H]D‐aspartate ([^3^H]D‐ASP) and exposed in superfusion to varying concentrations of NMDA in the presence of 1 μM glycine. The release of [^3^H]D‐ASP and also that of endogenous glutamate provoked by 10 μM NMDA were external Ca^2+^ dependent and sensitive to the NMDA channel blocker MK‐801 but insensitive to the glutamate transporter inhibitor DL‐TBOA, which, on the contrary, prevented the Ca^2+^‐independent release evoked by 100 μM NMDA. The NMDA (10 μM) response was blocked by 1 nM Zn^2+^ and 1 μM ifenprodil, compatible with the involvement of a NR1/NR2A/NR2B assembly, although the presence of two separate receptor populations, i.e., NR1/NR2A and NR1/NR2B, cannot be excluded. This response was strongly antagonized by submicromolar (0.01–1 μM) concentrations of kynurenic acid and was mimicked by quinolinic acid (1–100 μM) plus 1 μM glycine. Finally, the HIV‐1 protein gp120 potently mimicked the NMDA coagonists glycine and D‐serine, being significantly effective at 30 pM. In conclusion, glutamatergic nerve terminals possess NMDA autoreceptors mediating different types of release when activated by different agonist concentrations: low‐micromolar glutamate would potentiate glutamate exocytosis, whereas higher glutamate concentrations would also provoke carrier‐mediated release. © 2007 Wiley‐Liss, Inc.