Dexamethasone Potentiates Serotonin-2 Receptor-Mediated Intracellular Ca²⁺ Mobilization in C6 Glioma Cells

Abstract

Serotonin (5-hydroxytryptamine; 5-HT) caused a transient increase in intracellular Ca²⁺ in C6BU-1 glioma cells in a concentration-dependent manner; half maximally at 73 nM. The 5-HT₂ agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane also increased the levels of intracellular Ca²⁺ whereas the 5-HTιc agonist l-(3-chlorophenyl)piperazine and 5-HT_1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin were completely ineffective. Ketanserin and spiperone blocked the response to 5-HT at a nanomolar concentration, but the 5-HT3 antagonist MDL 72222 had no effect on it. Thus 5-HT₂ receptors are responsible for activating Ca²⁺ mobilization in C6 glioma cells. Treatment of C6 glioma cells with dexamethasone potentiated the ability of 5-HT to cause intracellular Ca²⁺ mobilization in both a dose- and time-dependent manner. The dose-response curve for 5-HTwas shifted 9-fold to the left compared to controls, and the V_max value was also significantly enhanced. This enhanced Ca²⁺ mobilization was completely inhibited by ketanserin dose-dependently. In addition, the treatment with dexamethasone enhanced fluoride-activated Ca²⁺ mobilization, suggesting that the enhanced GTP binding protein function is one of the mechanisms responsible for the enhancement of the 5-HT response induced by dexamethasone treatment. This enhancement of agonist activity was mediated by the type II glucocorticoid receptor (GR) since RU 38486, an inhibitor of the type II GR, antagonized the dexamethasone-induced enhancement.

Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck

“…2,27,28 Here, we report the rapid nongenomic effect of the synthetic GC, DM, on the early signaling events typically initiated by TCR ligation in T cells. Previous studies have reported that DM or GC treatment can inhibit TCR-mediated signaling responses, [28][29][30][31][32] including Lck, Fyn, and ZAP70 phosphorylation within activated T cells. 7 We have observed similar effects on activated T cells where DM treatment resulted in decreased Lck phosphorylation in this manuscript.…”

Fluoride Effects: The Two Faces of Janus

“…For instance, on one hand fluoride (5-10 mM, 95-190 mg/l) has been observed to inhibit directly, in rat skeletal muscle, the tyrosine kinase activity of the insulin receptor [79], and aluminum fluoride (3 mM, 57 mg/l fluoride) inhibits phospholipase D (PLD) in rat submandibular cells by a G protein-independent mechanism, which could be a regulatory protein of PLD or PLD itself [80]. On the other hand, in C6 rat glioma cells, sodium fluoride (10 mM, 190 mg/l fluoride) activated Gs or inhibited Gi to increase the cAMP concentration [81,82] and enhanced the cGMP generation via calcium/calmodulin-and nitric oxide synthase-dependent pathways [82], and the activation of G proteins by fluoride (1-20 mM, 19-380 mg/l) in smooth muscle cells initiated a series of events, including calcium mobilization, phospholipase C activation and protein kinase C activation [83,84]. At high concentrations sodium fluoride (600 mM, 11.4 g/l) inhibits also serine/threonine phosphatases [85].…”

Repeated Administration of Dexamethasone Increases Phosphoinositide‐Specific Phospholipase C Activity and mRNA and Protein Expression of the Phospholipase C β1 Isozyme in Rat Brain

“…Furthermore, in vitro studies show that DEX causes changes in PI metabolism. For example, Muraoka et al (1993) found that in vitro addition of DEX caused 5‐HT 2A receptor‐mediated Ca 2+ mobilization in C6 glioma cells, whereas Takahashi et al (1996) reported a decrease in norepinephrine‐stimulated PI metabolism after chronic DEX administration to rats. Recently, we observed that administration of DEX for 10 days caused a significant increase in [ 3 H]phorbol 12,13‐dibutyrate binding to PKC and in the immunolabeling of PKC γ and ε isozymes in rat cortex and hippocampus (Dwivedi and Pandey, 1998).…”