title: Effects of some new antidepressant drugs on the glucocorticoid receptor-mediated gene transcription in fibroblast cells.
abstract: Antidepressant drugs are thought to counteract effects of hypercortisolemia, frequently associated with depression, by lowering cortisol level and by modifying the function of glucocorticoid receptors (GR). Indeed, classical antidepressants inhibit corticosteroid-induced gene transcription in cell cultures. The aim of the present study was to investigate effects of new generation antidepressant drugs on GR function in mouse fibroblast cells (L929), stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCAT cells). It has been found that reboxetine (at 10 and 30 microM), venlafaxine, citalopram and mirtazapine (at 30 microM), but not milnacipran, in statistically significant manner inhibited corticosterone-induced gene transcription. However, the effects of new generation antidepressant drugs were weaker than those evoked by imipramine, which was active already at 3 microM concentration. Further studies on the mechanism of antidepressant action on GR function revealed that protein kinase C, but not mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK-3) and protein kinase B (PKB, Akt) play a role in this phenomenon.
authors.affiliation: Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
authors.forename: Matylda
authors.initials: M
authors.lastname: Augustyn
authors.forename: Magdalena
authors.initials: M
authors.lastname: Otczyk
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Jagła
authors.forename: Wojciech
authors.initials: W
authors.lastname: Nowak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
authors.forename: Lucylla
authors.initials: L
authors.lastname: Jaworska-Feil
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
authors.forename: Magdalena
authors.initials: M
authors.lastname: Tetich
authors.forename: Monika
authors.initials: M
authors.lastname: Leśkiewicz
authors.forename: Władysław
authors.initials: W
authors.lastname: Lasoń
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003345:Corticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007099:Imipramine / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077593:Reboxetine; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D000928:Antidepressive Agents; D005419:Flavonoids; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D011965:Receptors, Glucocorticoid; D000077593:Reboxetine; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D007099:Imipramine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D003345:Corticosterone