Serine released from hippocampal slices during deprivation of oxygen and glucose enhances the effects of glutamate on neuronal function.
Using guinea-pig hippocampal slices, we determined the amount of various amino acids released into the medium during deprivation of oxygen and glucose. Within 10 min of slices being deprived of O2 and glucose, the amounts of serine, aspartate, alanine, glycine, GABA, taurine and threonine released into the medium increased up to 1.7 (serine), 1.6 (aspartate), 1.6 (alanine), 1.9 (glycine), 2.0 (GABA), 1.4 (taurine) and 1.8 (threonine) times the control levels, respectively. The amount of serine released 10 min after O2 and glucose deprivation was four times as great as that of glutamate. The dose-response effects of glutamate and serine were studied on the population spikes evoked in the granular cell layer. Bath application of 100 microM serine elevated the amplitude of the population spike to 117% and at 10 mM depressed it completely. The dose-response curve for glutamate displayed a similar pattern but the effectiveness was 10 times higher than that of serine. The combined application of glutamate (300 microM) and serine (2 mM) produced a dramatic reduction in and depression of the amplitude of the population spike, although 300 microM glutamate and 2 mM serine individually failed to show a significant effect. The population spike was depressed by the addition of 1 mM glutamate but, after washing, it recovered completely. On the other hand treatment with 1 mM glutamate together with 5 mM serine caused no recovery of the population spike even after removal of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirai
H
H
Department of Physiology, Kobe University School of Medicine, Japan.
Okada
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010725:Phosphocreatine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012694:Serine / Q000378:metabolism* / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D000596:Amino Acids; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D010725:Phosphocreatine; D018698:Glutamic Acid; D012694:Serine; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; D007736:Kynurenic Acid; D005947:Glucose; C057013:7-chlorokynurenic acid