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

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Title: A presynaptic N-methyl-d-aspartate autoreceptor in rat hippocampus modulating amino acid release from a cytoplasmic pool.
Authors: Breukel, Alexandra I. M., Besselsen, Elly, da Silva, Fernando H. Lopes, Ghijsen, Wim E. J. M.
Source: European Journal of Neuroscience. Jan1998, Vol. 10 Issue 1. 1 Black and White Photograph, 7 Graphs.
Subjects: Methyl aspartate, Hippocampus (Brain), Rats
Abstract: 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 Mg[sup 2+], 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 Mg[sup 2+] (1 mm), was slow in onset and returned to baseline after NMDA-removal. The NMDA-effect was also found in the absence of extracellular Ca[sup 2+], suggesting that amino acids were released from a non-vesicular (cytoplasmic) pool. Secondly, in KCl-depolarized synaptosomes exposed to 1 mm Mg[sup 2+], NMDA did not affect the release of the amino acids. MK801, however, reduced the KCl-evoked Ca[sup 2+]-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[sup +]-entry, which may induce reversal of amino acid transporters and thereby releasing amino acids from a cytoplasmic pool. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Group: Ti
  Data: A presynaptic N-methyl-d-aspartate autoreceptor in rat hippocampus modulating amino acid release from a cytoplasmic pool.
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  Data: <searchLink fieldCode="AR" term="%22Breukel%2C+Alexandra+I%2E+M%2E%22">Breukel, Alexandra I. M.</searchLink><br /><searchLink fieldCode="AR" term="%22Besselsen%2C+Elly%22">Besselsen, Elly</searchLink><br /><searchLink fieldCode="AR" term="%22da+Silva%2C+Fernando+H%2E+Lopes%22">da Silva, Fernando H. Lopes</searchLink><br /><searchLink fieldCode="AR" term="%22Ghijsen%2C+Wim+E%2E+J%2E+M%2E%22">Ghijsen, Wim E. J. M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Jan1998, Vol. 10 Issue 1. 1 Black and White Photograph, 7 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Methyl+aspartate%22">Methyl aspartate</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Rats%22">Rats</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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 Mg[sup 2+], 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 Mg[sup 2+] (1 mm), was slow in onset and returned to baseline after NMDA-removal. The NMDA-effect was also found in the absence of extracellular Ca[sup 2+], suggesting that amino acids were released from a non-vesicular (cytoplasmic) pool. Secondly, in KCl-depolarized synaptosomes exposed to 1 mm Mg[sup 2+], NMDA did not affect the release of the amino acids. MK801, however, reduced the KCl-evoked Ca[sup 2+]-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[sup +]-entry, which may induce reversal of amino acid transporters and thereby releasing amino acids from a cytoplasmic pool. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1046/j.1460-9568.1998.00008.x
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      – Code: eng
        Text: English
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      – SubjectFull: Methyl aspartate
        Type: general
      – SubjectFull: Hippocampus (Brain)
        Type: general
      – SubjectFull: Rats
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      – TitleFull: A presynaptic N-methyl-d-aspartate autoreceptor in rat hippocampus modulating amino acid release from a cytoplasmic pool.
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            NameFull: Breukel, Alexandra I. M.
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            NameFull: Besselsen, Elly
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            NameFull: da Silva, Fernando H. Lopes
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            NameFull: Ghijsen, Wim E. J. M.
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            – D: 01
              M: 01
              Text: Jan1998
              Type: published
              Y: 1998
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