Effect of citalopram on the desensitization of serotonin-2A receptor-mediated calcium mobilization in rat glioma cells.
1. The authors have investigated the effect of citalopram, an effective antidepressant drug with selective serotonin (5-HT) uptake inhibition, on 5-HT-2A receptor-mediated intracellular calcium (Ca2+) rise in C6 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 receptors. 3. Citalopram did not alter a subsequent response to 5-HT after citalopram was pre-applied to the cells. 4. However, citalopram inhibited the desensitization of 5-HT-2A receptors. When the cells were pretreated with citalopram and 5-HT, the subsequent response to 5-HT was significantly greater than that obtained following pretreatment with 5-HT alone. 5. To investigate the mechanism of action of citalopram on the desensitization of 5-HT-2A receptors, NaF-induced cGMP generation was measured. Citalopram inhibited the generation of cGMP induced by NaF in C6 cells as well as W-7. 6. These results indicate that citalopram antagonized the desensitization of 5-HT-2A receptor-mediated Ca2+ mobilization and this antagonism may be mediated by a calmodulin-dependent pathway in C6 glioma cells.
Kagaya
A
A
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Minamiku, Hiroshima, Japan.
Kugaya
A
A
Hayashi
T
T
Okamoto
Y
Y
Takebayashi
M
M
Uchitomi
Y
Y
Yamawaki
S
S
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011985:Receptors, Serotonin; D015283:Citalopram; D002118:Calcium