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Pharmacopsychiatry 2011; 44: S27-S34
DOI: 10.1055/s-0031-1271704
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Modulation of Ligand-Gated Ion Channels as a Novel Pharmacological Principle

C. Nothdurfter1 , 2 , S. Tanasic2 , G. Rammes2 , 3 , R. Rupprecht1 , 2
  • 1Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Germany
  • 2Max-Planck-Institute of Psychiatry, Munich, Germany
  • 3Department of Anesthesiology, Technische Universität München, Munich, Germany
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Publication History

Publication Date:
04 May 2011 (online)

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Abstract

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 [3H]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.

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Correspondence

C. NothdurfterMD 

Department of Psychiatry and

Psychotherapy

Ludwig-Maximilians-University

Munich

Nußbaumstraße 7

80336 Munich

Germany

Phone: +49/89/5160 5881

Fax: +49/89/5160 5391

Email: Caroline.Nothdurfter@med.uni-muenchen.de