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Effect of valproic acid on serotonin‐2A receptor signaling in C6 glioma cells
Author(s) -
Sullivan N. R.,
Burke T.,
SiafakaKapadai A.,
Javors M.,
Hensler J. G.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02690.x
Subject(s) - receptor , ketanserin , phospholipase c , activator (genetics) , signal transduction , 5 ht receptor , chemistry , serotonin , inositol , endocrinology , medicine , pharmacology , biology , biochemistry
Valproic acid (VPA), which has demonstrated efficacy in the treatment of bipolar disorder, has been shown to alter components of the phosphoinositide (PI) signaling cascade and to increase gene expression mediated by the transcription factor activator protein 1 (AP‐1). Central serotonin‐2A (5‐HT 2A ) receptors, which have been implicated in the pathophysiology of manic‐depressive illness, are coupled to PI hydrolysis. The promoter region of the 5‐HT 2A receptor gene contains AP‐1 binding sites. We examined in C6 glioma cells the effect of VPA on 5‐HT 2A receptor signaling. Treatment of cells with VPA (100 µg/mL) for 20 h, but not 1.5 h, resulted in an enhancement of 5‐HT 2A receptor‐stimulated PI hydrolysis. This effect of 20‐h VPA exposure appeared not to be at the level of G protein or effector (i.e. phospholipase C: PLC) as inositol phosphate accumulation stimulated by aluminum fluoride or the PLC activator 2,4,6‐trimethyl‐ N ‐(m‐3‐trifluromethylphenyl) benzenesulfonamide was not increased. The number of 5‐HT 2A receptors, as determined in saturation binding experiments using [ 3 H]ketanserin, was increased by 20‐h VPA treatment, with no change in affinity ( K D ). Taken together, our data suggest that the increase in 5‐HT 2A receptor‐mediated PI hydrolysis following 20‐h VPA exposure is not due to a general effect of VPA on this signaling cascade, but due to the up‐regulation of 5‐HT 2A receptor number.