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

J Neurochem. 1993 Nov;61(5):1692-7. doi: 10.1111/j.1471-4159.1993.tb09805.x.


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).

MeSH terms

  • Animals
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Gestational Age
  • Glutamates / pharmacology
  • Glutamic Acid
  • Glycine / pharmacology*
  • Kinetics
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • N-Methylaspartate / pharmacology*
  • Pregnancy
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glycine / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Rhombencephalon / metabolism*
  • Serotonin / metabolism*
  • Strychnine / pharmacology
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Glutamates
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • Serotonin
  • Glutamic Acid
  • N-Methylaspartate
  • 2-amino-5-phosphopentanoic acid
  • Kynurenic Acid
  • Strychnine
  • Valine
  • 7-chlorokynurenic acid
  • Glycine