Vitamin E Reduces Antidepressant-Related β-Adrenoceptor Down-Regulation in Cultured Cells. Comparable Effects on St. John’s Wort and Tricyclic Antidepressant Treatment

 

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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 β-adrenoceptor (β-AR) numbers were consistently observed in vivo, while a reduction in surface β-AR density was found in cell cultures. Effects of the tricyclic antidepressant desipramine (DMI) were abolished by vitamin E (α-TOC) in vitro as well as in vivo. α-TOC interfered with antidepressant-induced changes of cellular plasma membrane properties and with recycling of β-AR. St. John’s wort (SJW) extract reduced β-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 α-TOC. Receptor down-regulation following exposure to the plant extract was inhibited in the presence of α-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 α-TOC.

Abbreviations

α-TOC:α-Tocopherol, vitamin E

β-AR:β-Adrenoceptor

C6 cells:Rat glioma C6 cells

DMI:Desipramine

SD:Standard Deviation

SJW:Saint John's Wort

SSRI:Selective Serotonin Reuptake Inhibitors

TCA:Tricyclic Antidepressants

Ze 117 extract:Saint John's Wort extract Ze 117

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Prof. Dr. U. Honegger

Department of Pharmacology

University of Bern

Friedbuehlstr. 49

3010 Bern

Switzerland

Fax: +41-31-632-4992

Email: ulrich.honegger@pki.unibe.ch