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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT 2A receptor activation
Author(s) -
Meller R.,
Harrison P.J.,
Elliott J.M.,
Sharp T.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10126
Subject(s) - glutamate receptor , quipazine , agonist , 5 ht receptor , receptor , pharmacology , chemistry , efflux , ketanserin , receptor antagonist , biology , biochemistry , serotonin , antagonist
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 μM). The 5‐HT 2A receptor antagonists ketanserin (1 μM) and spiperone (1 μM) 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 μM). 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 μM) 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. © 2002 Wiley‐Liss, Inc.