title: Vitamin E reduces antidepressant-related beta-adrenoceptor down-regulation in cultured cells. Comparable effects on St. John's wort and tricyclic antidepressant treatment.
abstract: The mode of action of antidepressants is still a matter of debate. Acute inhibition of neurotransmitter reuptake in central neuronal synapses, followed by a down-regulation of central postsynaptic beta-adrenoceptor (beta-AR) numbers were consistently observed in vivo, while a reduction in surface beta-AR density was found in cell cultures. Effects of the tricyclic antidepressant desipramine (DMI) were abolished by vitamin E (alpha-TOC) in vitro as well as in vivo. Alpha-TOC interfered with antidepressant-induced changes of cellular plasma membrane properties and with recycling of beta-AR. St. John's wort (SJW) extract reduced beta-AR numbers in cultured cells to a similar extent as DMI or the selective serotonin re-uptake inhibitor fluoxetine. We chronically co-exposed cell cultures to SJW extract and to alpha-TOC. Receptor down-regulation following exposure to the plant extract was inhibited in the presence of alpha-TOC suggesting a mode of action of SJW extract comparable to that of synthetic antidepressants. Inhibition of cell proliferation by the plant extract was also significantly reduced by alpha-TOC.
authors.affiliation: Department of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: De Marchis
authors.forename: Sibylle
authors.initials: S
authors.lastname: Bürgi
authors.forename: Urs
authors.initials: U
authors.lastname: Kientsch
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Honegger
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D015536:Down-Regulation; D004357:Drug Synergism; D020902:Hypericum; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D010936:Plant Extracts; D011943:Receptors, Adrenergic, beta; D014810:Vitamin E