期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 85, 期 16, 页码 3657-3665出版社
WILEY
DOI: 10.1002/jnr.21446
关键词
NMDA autoreceptors; glutamate release; exocytosis; carrier-mediated release; rat hippocampus
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 Ca2+ -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 [H-3]D-aspartate ([H-3]D-ASP) and exposed in superfusion to varying concentrations of NMDA in the presence of 1 mu M glycine. The release of [3 H]D-ASP and also that of endogenous glutamate provoked by 10 mu M NMDA were external Ca2+ 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 Ca2+ - independent release evoked by 100 mu M NMDA. The NMDA (10 mu M) response was blocked by 1 nM Zn2+ and 1 mu M ifenprodil, compatible with the involvement of a NRl/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 mu M) concentrations of kynurenic acid and was mimicked by quinolinic acid (1-100 mu M) plus 1 mu M 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. (C) 2007 Wiley-Liss, Inc.
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