DEXAMETHASONE POTENTIATES SEROTONIN-2 RECEPTOR-MEDIATED INTRACELLULARCA2-CELLS( MOBILIZATION IN C6 GLIOMA)

Serotonin (5-hydroxytryptamine; 5-HT) caused a transient increase in i ntracellular 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-dimet hoxyphenyl)-2-aminopropane also increased the levels of intracellular Ca2+, whereas the 5-HT1C agonist 1-(3-chlorophenyl)piperazine and 5-HT 1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin were completely inef fective. Ketanserin and spiperone blocked the response to 5-HT at a na nomolar concentration, but the 5-HT3 antagonist MDL 72222 had no effec t on it. Thus 5-HT2 receptors are responsible for activating Ca2+ mobi lization in C6 glioma cells. Treatment of C6 glioma cells with dexamet hasone potentiated the ability of 5-HT to cause intracellular Ca2+ mob ilization 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, a nd 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-acti vated Ca2+ mobilization, suggesting that the enhanced GTP binding prot ein function is one of the mechanisms responsible for the enhancement of the 5-HT response induced by dexamethasone treatment. This enhancem ent of agonist activity was mediated by the type II glucocorticoid rec eptor (GR) since RU 38486, an inhibitor of the type II GR, antagonized the dexamethasone-induced enhancement.