Characterization of the 5-hydroxytryptamine2A receptor-activated cascade in rat c6 glioma cells

Elliott, J.M.; Newberry, Nigel R.; Cholewinski, A.; Bartrup, J.T.; Briddon, Stephen J.; Carey, Jae E.; Flanigan, Thomas P.; Newton, Rebecca; Phipps, S. L.; Reavley, A.C.; Smith, Christopher W.; Wigmore, M.A.; Grahame-Smith, David G.; Leslie, R.A.

doi:10.1016/0306-4522(95)00323-b

Cited by 28 publications

(17 citation statements)

References 34 publications

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“…On the basis of its affinity for the receptors in ligand binding studies, 1 M SB 200646 would be expected to block both the 5-HT 2B and the 5-HT 2C receptors, with receptor occupancies of 97% and 88%, respectively, but not the 5-HT 2A receptor (14% receptor occupancy; Kennet, 1993). These findings are consistent with previous reports that demonstrate the expression of 5-HT 2A receptors by C6 glioma cells (Ogura et al, 1986;Ananth et al, 1987;Bartrup and Newberry, 1994;Elliott et al, 1995;Kagaya et al, 1995;Pauwels et al, 1996).…”

Section: Discussionsupporting

confidence: 95%

“…The pharmacological profile of the 5-HT receptor expressed by C6 glioma cells has been found to be identical to that of the 5-HT 2A receptor found in rat brain (Elliott et al, 1995). 5-HT acting upon the 5-HT 2A receptor stimulates phosphoinositide hydrolysis, and the liberated inositol 1,4,5-triphosphate (IP 3 ) promotes the release of calcium from intracellular stores (Ogura et al, 1986;Reiser et al, 1989;Deecher et al, 1993;Elliott et al, 1995;Cholewinski and Leslie, 1996). It has been suggested that transmitter-evoked increases in intracellular calcium may trigger the exocytotic release of glutamate from glial cells (Parpura et al, 1994;Bezzi et al, 1998).…”

mentioning

confidence: 91%

“…Recent data suggest that glial cells may also be a target for 5-HT released by neurons (Kimelberg, 1995). Several groups have shown that glial cells in culture express various 5-HT receptor subtypes, in particular, the 5-HT 2A receptor subtype (Deecher et al, 1993;Kimelberg, 1995;Elliott et al, 1995;Merzak et al, 1996) as well as the 5-HT 1A (Merzak et al, 1996;Azmitia et al, 1996), 5-HT 5 (Carson et al, 1996), and 5-HT 6 and 5-HT 7 (Hirst et al, 1998;Shimizu et al, 1998) receptor subtypes. It has recently been shown that astrocytes in the central nervous system (CNS) in situ express 5-HT 2A receptors, under both normal and pathophysiological conditions (Hamada et al, 1998;Wu et al, 1999;Eastwood et al, 2001).…”

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confidence: 98%

“…Here we describe the effect of 5-HT, 5-HT 2 agonists, and other drugs that raise glial intracellular calcium, on the efflux of glutamate from C6 glioma cells. C6 glioma cells were used because of their well-characterized calcium response following 5-HT 2A receptor activation (Elliott et al, 1995).…”

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confidence: 99%

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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation

Meller

Harrison

Elliott

et al. 2002

J of Neuroscience Research

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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.

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Section: Discussionsupporting

confidence: 95%

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confidence: 91%

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confidence: 98%

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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation

Meller

Harrison

Elliott

et al. 2002

J of Neuroscience Research

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“…To clarify which 5-HT receptor subtypes were related to the effect of 5-HT, we examined the effects of antagonists for 5-HT 2A and 5-HT 1A receptors (ketanserin and WAY100635) on the 5-HT-induced ERK activation. Several reports demonstrated that C6 cells functionally express 5-HT 2A and 5-HT 1A receptors (Shinagawa, 1994;Elliott et al, 1995). Ketanserin, but not WAY100635, completely inhibited the 5-HT-induced ERK activation in C6 cells (Fig.…”

Section: Mechanism Of Gdnf Production By Antidepressants 151mentioning

confidence: 78%

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Hisaoka¹,

Takebayashi²,

Tsuchioka³

et al. 2007

J Pharmacol Exp Ther

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Recent studies show that neuronal and glial plasticity are important for therapeutic action of antidepressants. We previously reported that antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production in rat C6 glioma cells (C6 cells). Here, we found that amitriptyline, a tricyclic antidepressant, increased both GDNF mRNA expression and release, which were selectively and completely inhibited by mitogen-activated protein kinase kinase inhibitors. Indeed, treatment of amitriptyline rapidly increased extracellular signal-regulated kinase (ERK) activity, as well as p38 mitogen-activated protein kinase and c-Jun NH 2 -terminal kinase activities. Furthermore, different classes of antidepressants also rapidly increased ERK activity. The extent of acute ERK activation and GDNF release were significantly correlated to each other in individual antidepressants, suggesting an important role of acute ERK activation in GDNF production. Furthermore, antidepressants increased the acute ERK activation and GDNF mRNA expression in normal human astrocytes as well as C6 cells. Although 5-hydroxytryptamine (serotonin) (5-HT), but not noradrenaline or dopamine, increased ERK activation and GDNF release via 5-HT 2A receptors, ketanserin, a 5-HT 2A receptor antagonist, did not have any effect on the amitriptyline-induced ERK activation. Thus, GDNF production by amitriptyline was independent of monoamine. Both of the amitriptyline-induced ERK activation and GDNF mRNA expression were blocked by genistein, a general protein tyrosine kinase (PTK) inhibitor. Actually, we found that amitriptyline acutely increased phosphorylation levels of several phosphotyrosine-containing proteins. Taken together, these findings indicate that ERK activation through PTK regulates antidepressant-induced GDNF production and that the GDNF production in glial cells may be a novel action of the antidepressant, which is independent of monoamine.Major depression is a common and severe illness affecting a large number of individuals during their lifetime, and it is primarily treated with antidepressants. Most of the antidepressants are known to inhibit 5-hydroxytryptamine (serotonin, 5-HT) and/or noradrenaline (NA) reuptake; however, the efficacy of these antidepressants cannot be solely explained by their actions on the monoaminergic system. The molecular and cellular adaptations that underlie the therapeutic action of antidepressants have remained obscure. ; JNK, c-Jun NH 2 -terminal protein kinase; LDH, lactate dehydrogenase; ANOVA, analysis of variance; PLSD, protected least significant difference; HSD, honestly significant difference; MEK, mitogen-activated protein kinase kinase; PKA, protein kinase A; PKC, protein kinase C; DA, dopamine; PI3K, phosphoinositide-3 kinase; SP600125, anthra(1,9-cd)pyrazol-6(2H)-one.

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Pertussis toxin treatment prevents 5-HT5a receptor-mediated inhibition of cyclic AMP accumulation in rat C6 glioma cells

Thomas¹,

Matli²,

Hu³

et al. 2000

J. Neurosci. Res.

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Characterization of the 5-hydroxytryptamine2A receptor-activated cascade in rat c6 glioma cells

Cited by 28 publications

References 34 publications

In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation

In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Pertussis toxin treatment prevents 5-HT5a receptor-mediated inhibition of cyclic AMP accumulation in rat C6 glioma cells

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Characterization of the 5-hydroxytryptamine2A receptor-activated cascade in rat c6 glioma cells

Cited by 28 publications

References 34 publications

In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT2A receptor activation

In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT2A receptor activation

Antidepressants Increase Glial Cell Line-Derived Neurotrophic Factor Production through Monoamine-Independent Activation of Protein Tyrosine Kinase and Extracellular Signal-Regulated Kinase in Glial Cells

Pertussis toxin treatment prevents 5-HT5a receptor-mediated inhibition of cyclic AMP accumulation in rat C6 glioma cells

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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation

In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation