Dexamethasone potentiates serotonin-2 receptor-mediated intracellular Ca2+ mobilization in C6 glioma cells.
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-HT1C agonist 1-(3-chlorophenyl)piperazine and 5-HT1A 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-HT was shifted 9-fold to the left compared to controls, and the Vmax 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.
Division of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
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S
Muraoka
M
M
Mikuni
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A
Kagaya
K
K
Saitoh
K
K
Takahashi
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013134:Spiperone; D003907:Dexamethasone; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D002118:Calcium