[Effects of chronic valproic acid sodium treatment and withdrawal on glutamate and glutamine release of C6 glioma cells].
OBJECTIVE
To determine the effects of chronic valproic acid sodium (VPA) treatment and subsequent withdrawal on the release of glutamate (Glu) and glutamine (Gln) by C6 glioma cells, so as to understand the role of Glu and Gln released by astrocytes in the antiepileptic mechanism of VPA and the rebound mechanism of VPA withdrawal.


METHODS
C6 glioma cells were maintained for 2 weeks in DMEM medium containing 50 mg/L VPA to establish the cell model of chronic VPA treatment. High-performance liquid chromatography (HPLC) was performed to detect the levels of Glu and Gln released by C6 glioma cells after chronic VPA treatment and subsequent withdrawal.


RESULTS
Chronic VPA treatment increased Glu release of C6 glioma cells, and subsequent VPA withdrawal resulted in sustained decrease in the Glu level, reaching the lowest level 12 h after VPA withdrawal, which was obviously lower than the control level. Gradual but significant increase of Glu level was then observed to approach the control level till 48 h after VPA withdrawal. For Gln release, chronic VPA treatment resulted in its decrease while after VPA withdrawal, gradual increase occurred to recover the control level.


CONCLUSIONS
Chronic VPA treatment can increase Glu and decrease Gln release by C6 glioma cells. Glu level undergoes a rebound in response to VPA withdrawal, while the relatively even changes of Gln level in the same setting may not involve VPA withdrawal rebound mechanism.
Gao
Yang
Y
Institute of Pharmaceutic Science, First Military Medical University, Guangzhou 510515, China.
Lei
Lin-sheng
LS
Wu
Shu-guang
SG
D000927:Anticonvulsants / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D005973:Glutamine; D018698:Glutamic Acid; D014635:Valproic Acid