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rdf:type |
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lifeskim:mentions |
umls-concept:C0015283,
umls-concept:C0019564,
umls-concept:C0030685,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0079883,
umls-concept:C0086045,
umls-concept:C0205251,
umls-concept:C0206128,
umls-concept:C0220839,
umls-concept:C0243192,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1553423,
umls-concept:C1963578
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pubmed:issue |
16
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pubmed:dateCreated |
2007-12-6
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pubmed:abstractText |
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 microM glycine. The release of [(3)H]D-ASP and also that of endogenous glutamate provoked by 10 microM 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 microM NMDA. The NMDA (10 microM) response was blocked by 1 nM Zn(2+) and 1 microM 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 microM) concentrations of kynurenic acid and was mimicked by quinolinic acid (1-100 microM) plus 1 microM glycine. Finally, the HIV-1 protein gp120 potently mimicked the NMDA co-agonists 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Autoreceptors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/HIV Envelope Protein gp120,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/NR1 NMDA receptor,
http://linkedlifedata.com/resource/pubmed/chemical/NR2A NMDA receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Glutamate Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxyaspartate
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0360-4012
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2007 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3657-65
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pubmed:meshHeading |
pubmed-meshheading:17671992-Animals,
pubmed-meshheading:17671992-Aspartic Acid,
pubmed-meshheading:17671992-Autoreceptors,
pubmed-meshheading:17671992-Dose-Response Relationship, Drug,
pubmed-meshheading:17671992-Excitatory Amino Acid Agonists,
pubmed-meshheading:17671992-Excitatory Amino Acid Antagonists,
pubmed-meshheading:17671992-Exocytosis,
pubmed-meshheading:17671992-Glutamic Acid,
pubmed-meshheading:17671992-Glycine,
pubmed-meshheading:17671992-HIV Envelope Protein gp120,
pubmed-meshheading:17671992-Hippocampus,
pubmed-meshheading:17671992-Male,
pubmed-meshheading:17671992-N-Methylaspartate,
pubmed-meshheading:17671992-Presynaptic Terminals,
pubmed-meshheading:17671992-Rats,
pubmed-meshheading:17671992-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:17671992-Synaptic Transmission,
pubmed-meshheading:17671992-Synaptosomes,
pubmed-meshheading:17671992-Vesicular Glutamate Transport Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Pharmacology and Toxicology Section, Department of Experimental Medicine, University of Genoa, Viale Cembrano 4, Genoa, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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