Vitamin E reduces antidepressant-related beta-adrenoceptor down-regulation in cultured cells. Comparable effects on St. John's wort and tricyclic antidepressant treatment.

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.

Plasmalogen content and beta-adrenoceptor signalling in fibroblasts from patients with Zellweger syndrome. Effects of hexadecylglycerol.

In Zellweger or cerebro-hepato-renal syndrome (CHRS), the assembly of peroxisomes is defective, resulting in deficient plasmalogen formation. Plasmalogens are part of the membrane lipid composition. In fibroblasts of CHRS patients, the plasmalogen fraction of phosphatidylethanolamine (PPE) was about half of that in control cells while total phospholipid (PL) content, individual PL and plasma membrane fluidity were normal.

Antidepressant-induced switch of beta 1-adrenoceptor trafficking as a mechanism for drug action.

Reduction in surface beta(1)-adrenoceptor (beta1AR) density is thought to play a critical role in mediating the therapeutic long term effects of antidepressants. Since antidepressants are neither agonists nor antagonists for G protein-coupled receptors, receptor density must be regulated through processes independent of direct receptor activation. Endocytosis and recycling of the beta1AR fused to green fluorescent protein at its carboxyl-terminus (beta1AR-GFP) were analyzed by confocal fluorescence microscopy of live cells and complementary ligand binding studies.