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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents



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ID: 563801.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
Modulation of Ligand-Gated Ion Channels as a Novel Pharmacological Principle
Authors:Nothdurfter, C.; Tanasic, S.; Rammes, G.; Rupprecht, R.
Language:English
Date of Publication (YYYY-MM-DD):2011-05
Title of Journal:Pharmacopsychiatry
Volume:44
Issue / Number:Suppl. 1
Start Page:S27
End Page:S34
Review Status:not specified
Audience:Not Specified
Abstract / Description:The present study investigated the functional antagonism of different antidepressants on 5-HT3 receptor function and the role of lipid rafts for these modulatory effects. Electrophysiological recordings of 5-HT evoked cation currents were recorded with N1E-115 and HEK-5-HT3A cells and hippocampal neurons. The characterization of the antagonism of antidepressants was made by the displacement of [H-3]GR65630 binding. For membrane fractionation, sucrose density gradient centrifugation was used. Gradient fractions were assayed for antidepressant concentrations by HPLC; 5-HT3 receptor membrane distribution was determined by Western blot. Colocalization experiments were performed by means of immunocytochemistry. Most antidepressants acted as non-competitive antagonists at the 5-HT3 receptor. Moreover, some of these compounds were enriched within lipid rafts. Cholesterol depletion impaired lipid raft integrity thereby affecting 5-HT3 receptor function, whereas the antagonistic effects of antidepressants were not altered. In conclusion, most antidepressants directly antagonize 5-HT3 receptor activity. 5-HT3 receptor function per se appears to depend on lipid raft integrity, which is, however, not a prerequisite for the modulatory potency of antidepressants at this receptor.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
Identifiers:ISI:000290416000005 [ID No:1]
ISSN:0176-3679 [ID No:2]
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