Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Recent studies have established the presence of 5-hydroxytryptamine (5-HT)(2A) receptors on glial cells in culture and in the brain in situ. Here we used cultured C6 glioma cells to investigate the possibility that 5-HT(2A) receptors on glia regulate glutamate release from the cell. The efflux of endogenous glutamate from cultured C6 glioma cells was increased by addition of 5-HT in a concentration-dependent manner (maximal effect +200%). The efflux of serine and aspartate was not altered. The effect of 5-HT was mimicked by both the nonselective 5-HT receptor agonist quipazine and the selective 5-HT(2) receptor agonist 4-iodo-2,5-dimethoxyamphetamine (DOI; both 0.01-100 microM). The 5-HT(2A) receptor antagonists ketanserin (1 microM) and spiperone (1 microM) inhibited the glutamate response to 5-HT, quipazine, and DOI, whereas the effect of 5-HT was not inhibited by the 5-HT(2B/C) receptor antagonist SB200646 (1 microM). The effect of 5-HT on glutamate was specific in that it was reduced in low-calcium medium but was not prevented by furosemide (5 mM), which prevents cell swelling-induced glutamate release. Finally, the glutamate uptake inhibitor 2,4,trans-pyrollidine dicarboxylic acid (50 microM) did not block the 5-HT-induced efflux of glutamate, making involvement of glutamate transport unlikely. In conclusion, 5-HT stimulates the efflux of glutamate from C6 glioma cells following 5-HT(2A) receptor activation and involves a calcium-dependent mechanism.

Original publication




Journal article


J Neurosci Res

Publication Date





399 - 405


Animals, Bucladesine, Calcium, Cell Line, Chromatography, High Pressure Liquid, Culture Media, Conditioned, Dicarboxylic Acids, Diuretics, Dose-Response Relationship, Drug, Furosemide, Glutamic Acid, Neuroglia, Neurotransmitter Uptake Inhibitors, Pyrrolidines, Rats, Receptor, Serotonin, 5-HT2A, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Serotonin Receptor Agonists