EFFECT OF CITALOPRAM ON THE DESENSITIZATION OF SEROTONIN-2A RECEPTOR-MEDICATED CALCIUM MOBILIZATION IN RAT GLIOMA-CELLS

1. The authors have investigated the effect of citalopram, an effectiv e antidepressant drug with selective serotonin (5-HT) uptake inhibitio n, on 5-HT-2A receptor-mediated intracellular calcium (Ca2+) rise in C 6 cultured cells. 2. Citalopram, at concentrations of 10 and 30 mu M, did not significantly reduce the Ca2+ mobilization induced by 10 mu M 5-HT, indicating that citalopram has little affinity for 5-HT-2A recep tors. 3. Citalopram did not alter a subsequent response to 5-HT after citalopram was pre-applied to the cells. 4. However, citalopram inhibi ted the desensitization of 5-HT-2A receptors. When the cells were pret reated with citalopram and 5-HT, the subsequent response to 5-HT was s ignificantly greater than that obtained following pretreatment with 5- HT alone. 5. To investigate the mechanism of action of citalopram on t he desensitization of 5-HT-2A receptors, NaF-induced cGMP generation w as measured. Citalopram inhibited the generation of cGMP induced by Na F in CS cells as well as W-7. 6. These results indicate that citalopra m antagonized the desensitization of 5-HT-2A receptor-mediated Ca2+ mo bilization and this antagonism may be mediated by a calmodulin-depende nt pathway in C6 glioma cells.