Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Planta Med ; 72(15): 1436-7, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17109256

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.


Subject(s)
Antidepressive Agents/pharmacology , Hypericum , Phytotherapy , Plant Extracts/pharmacology , Receptors, Adrenergic, beta/metabolism , Vitamin E/pharmacology , Animals , Antidepressive Agents/administration & dosage , Antidepressive Agents/therapeutic use , Antidepressive Agents, Tricyclic/administration & dosage , Antidepressive Agents, Tricyclic/pharmacology , Antidepressive Agents, Tricyclic/therapeutic use , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Down-Regulation , Drug Synergism , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Rats , Vitamin E/administration & dosage , Vitamin E/therapeutic use
2.
J Biol Chem ; 278(2): 1044-52, 2003 Jan 10.
Article in English | MEDLINE | ID: mdl-12393876

ABSTRACT

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. In stably transfected C6 glioblastoma cells, beta1AR-GFP displayed identical ligand-binding isotherms and adenylyl cyclase activation as native beta1AR. Upon exposure to isoproterenol, a fraction of beta1AR-GFP (10-15%) internalized rapidly and colocalized with endocytosed transferrin receptors in an early endosomal compartment in the perinuclear region. Chronic treatment with the tricyclic antidepressant desipramine (DMI) did not affect internalization characteristics of beta1AR-GFP when challenged with isoproterenol. However, internalized receptors were not able to recycle back to the cell surface in DMI-treated cells, whereas recycling of transferrin receptors was not affected. Endocytosed receptors were absent from structures that stained with fluorescently labeled dextran, and inhibition of lysosomal protease activity did not restore receptor recycling, indicating that beta1AR-GFP did not immediately enter the lysosomal compartment. The data suggest a new mode of drug action causing a "switch" of receptor fate from a fast recycling pathway to a slowly exchanging perinuclear compartment. Antidepressant-induced reduction of receptor surface expression may thus be caused by modulation of receptor trafficking routes.


Subject(s)
Antidepressive Agents/pharmacology , Receptors, Adrenergic, beta-1/drug effects , Animals , Desipramine/pharmacology , Endocytosis/drug effects , Rats , Receptors, Adrenergic, beta-1/analysis , Receptors, Adrenergic, beta-1/metabolism , Receptors, Transferrin/metabolism , Recombinant Fusion Proteins/biosynthesis , Tumor Cells, Cultured
3.
Biochim Biophys Acta ; 1585(1): 39-43, 2002 Nov 08.
Article in English | MEDLINE | ID: mdl-12457713

ABSTRACT

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. CHRS cell strains had higher beta-adrenoceptor numbers and isoproterenol-stimulated cAMP responses. Receptors were more efficiently coupled to adenylate cyclase than in control cells. Stimulations of cAMP with NaF or forskolin were the same as in control cells. Restoring synthesis of plasmalogens with hexadecylglycerol (HDG), a plasmalogen precursor, resulted in a proportionate increase in PPE of about 40% in both control and CHRS fibroblasts. Exposure to HDG reduced surface beta-adrenoceptor sites and cAMP-responses to isoproterenol in CHRS cells only, while post-receptor stimulations of cAMP were reduced in both cell types. Plasmalogen contents inversely correlated with isoproterenol-stimulated cAMP levels. The increased numbers of functional beta-adrenoceptors in CHRS fibroblasts may be the result of a higher expression and/or of a prolonged functional half-life of the receptor protein. In vivo, this may contribute to the clinical manifestations of the disease.


Subject(s)
Plasmalogens/physiology , Receptors, Adrenergic, beta/physiology , Signal Transduction/physiology , Zellweger Syndrome/physiopathology , Cell Line , Cell Membrane/physiology , Fibroblasts/physiology , Humans , Peroxisomes/physiology , Phospholipid Ethers/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...