title: Effect of citalopram on the desensitization of serotonin-2A receptor-mediated calcium mobilization in rat glioma cells.
abstract: 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.
authors.affiliation: Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Minamiku, Hiroshima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kagaya
authors.forename: A
authors.initials: A
authors.lastname: Kugaya
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Takebayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Uchitomi
authors.forename: S
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: 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
chemical_list: D011985:Receptors, Serotonin; D015283:Citalopram; D002118:Calcium