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N‐methyl‐D‐aspartic acid/glycine interactions on the control of 5‐hydroxytryptamine release in raphe primary cultures

Abstract : Glutamic acid and glycine were quantified in cells and medium of cultured rostral rhombencephalic neurons derived from fetal rats. In the presence of 1 mM Mg2+, NMDA (50 microM) significantly stimulated (by 69%) release of newly synthesized 5‐[3H]hydroxytryptamine ([3H]5‐HT). D‐2‐Amino‐5‐phosphonopentanoate (AP‐5; 50 microM) blocked the stimulatory effect of NMDA. AP‐5 by itself inhibited [3H]5‐HT release (by 25%), suggesting a tonic control of 5‐HT by glutamate. In the absence of Mg2+, basal [3H]5‐HT release was 60% higher as compared with release with Mg2+. AP‐5 blocked the increased [3H]5‐HT release observed without Mg2+, suggesting that this effect was due to the stimulation of NMDA receptors by endogenous glutamate. Glycine (100 microM) inhibited [3H]5‐HT release in the absence of Mg2+. Strychnine (50 microM) blocked the inhibitory effect of glycine, indicating an action through strychnine‐sensitive inhibitory glycine receptors. The [3H]5‐HT release stimulated by NMDA was unaffected by glycine. In contrast, when tested in the presence of strychnine, glycine increased NMDA‐evoked [3H]5‐HT release (by 22%), and this effect was prevented by a selective antagonist of the NMDA‐associated glycine receptor, 7‐chlorokynurenate (100 microM). 7‐Chlorokynurenate by itself induced a drastic decrease in [3H]5‐HT release, indicating that under basal conditions these sites were stimulated by endogenous glycine. These results indicate that NMDA stimulated [3H]5‐HT release in both the presence or absence of Mg2+. Use of selective antagonists allowed differentiation of a strychnine‐sensitive glycine response (inhibition of [3H]5‐HT release) from a 7‐chlorokynurenate‐sensitive response (potentiation of NMDA‐evoked [3H]5‐HT release).
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https://hal.archives-ouvertes.fr/hal-01671966
Contributor : Denis Becquet <>
Submitted on : Friday, December 22, 2017 - 6:00:47 PM
Last modification on : Wednesday, April 3, 2019 - 1:56:17 AM

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  • HAL Id : hal-01671966, version 1
  • PUBMED : 7901329

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D. Becquet, M. Héry, P. Deprez, M. Faudon, M. P. Fache, et al.. N‐methyl‐D‐aspartic acid/glycine interactions on the control of 5‐hydroxytryptamine release in raphe primary cultures. Journal of Neurochemistry, 1993, 61 (5), pp.1692--1697. ⟨hal-01671966⟩

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