Τίτλος:
Effect of valproic acid on serotonin-2A receptor signaling in C6 glioma cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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-HT2A receptor gene contains AP-1 binding sites. We examined in C6 glioma cells the effect of VPA on 5-HT2A receptor signaling. Treatment of cells with VPA (100 μg/mL) for 20 h, but not 1.5 h, resulted in an enhancement of 5-HT2A 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 fiuoride or the PLC activator 2,4,6-trimethyl-N-(m-3- trifluromethylphenyl) benzenesulfonamide was not increased. The number of 5-HT2A receptors, as determined in saturation binding experiments using [3H]ketanserin, was increased by 20-h VPA treatment, with no change in affinity (KD). Taken together, our data suggest that the increase in 5-HT2A 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-HT2A receptor number.
Συγγραφείς:
Sullivan, N.R.
Burke, T.
Siafaka, A.
Kapadai
Javors, M.
Hensler, J.G.
Περιοδικό:
Journal of Neurochemistry
Λέξεις-κλειδιά:
1 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione; inositol; ketanserin; mepyramine maleate; methysergide maleate; phosphatidylinositide; phospholipase C; prazosin; quipazine; serotonin; serotonin 2A receptor; transcription factor AP 1; tritium; valproic acid, animal cell; article; binding affinity; bipolar disorder; controlled study; drug effect; genetic polymorphism; genetic transcription; glioma cell; mental disease; nonhuman; priority journal; psychopharmacology; rat; receptor gene; signal transduction, Animals; Anticonvulsants; Binding Sites; Cell Line; Dose-Response Relationship, Drug; Glioma; Ketanserin; Mice; Phosphatidylinositols; Quipazine; Receptor, Serotonin, 5-HT2A; Signal Transduction; Time Factors; Tritium; Valproic Acid, Animalia
DOI:
10.1111/j.1471-4159.2004.02690.x
