Glutamate-dependent glutamine, aspartate and serine release from rat cortical glial cell cultures

• Published in: Brain research 2003-07, Vol.978 (1), p.213-222
• Main Authors: Rao, Tadimeti S., Lariosa-Willingham, Karen D., Yu, Naichen
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Animals, Newborn; Anti-Inflammatory Agents - pharmacology; Aspartic Acid - metabolism; Biological and medical sciences; Cells, Cultured; Cerebral Cortex; Dexamethasone - pharmacology; Dicarboxylic Acids - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; Glia; Glutamate–glutamine cycle; Glutamic Acid - analysis; Glutamic Acid - pharmacology; Glutamine - metabolism; Isolated neuron and nerve. Neuroglia; Neuroglia - drug effects; Neuroglia - metabolism; Neurotransmitter Uptake Inhibitors - pharmacology; Pyrrolidines - pharmacology; Rats; Rats, Sprague-Dawley; Serine - metabolism; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)02841-5

Glia play a pivotal role in glutaminergic excitatory neurotransmission in the central nervous system by regulating synaptic levels of glutamate and by providing glutamine as the sole precursor for the neurotransmitter pool glutamate to neurons through the glutamate–glutamine cycle. In the present investigation, we examined the influence of glutamate application on glutamine, serine and aspartate release from rat cortical glial cultures. The glial glutamate transporters rapidly cleared exogenously applied glutamate and this was accompanied by rapid increases in aspartate and glutamine, and a delayed increase in serine levels in the glial-conditioned medium. While glutamate-induced increases in glutamine and serine were sustained for up to 24 h, increases in aspartate lasted only for up to 6 h. The glutamate-induced increases in aspartate and glutamine were dependent both on the concentration and the duration of glutamate stimulus, but were largely insensitive to the inhibition of non- N-methyl- d-aspartate receptors or the metabotropic glutamate receptor 5. Inhibition of the glutamate transporter function by l- trans-pyrrolidine 2,4-dicarboxylate decreased the rate of glutamate uptake but not completely abrogated the uptake process, and this resulted in the attenuation of rate of glutamate induced glutamine synthesis. Dexamethasone treatment increased serine and glutamine levels in conditioned medium and increased glutamate induced glutamine release suggesting an upregulation of glutamine synthase activity. These results further substantiate coupling between glutamate and glutamine, and shed light on glutamate-dependent release of serine and aspartate, which may further contribute to excitatory neurotransmission.