HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 2, 1044-1052, January 10, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/2/1044    most recent M209972200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bürgi, S. Articles by Honegger, U. E. Search for Related Content PubMed PubMed Citation Articles by Bürgi, S. Articles by Honegger, U. E. Social Bookmarking                      What's this?

Antidepressant-induced Switch of ₁-Adrenoceptor Trafficking as a Mechanism for Drug Action^*

Sibylle Bürgi, Kurt Baltensperger, and Ulrich E. Honegger

From the Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland

Reduction in surface ₁-adrenoceptor (1AR) 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 1AR fused to green fluorescent protein at its carboxyl-terminus (1AR-GFP) were analyzed by confocal fluorescence microscopy of live cells and complementary ligand binding studies. In stably transfected C6 glioblastoma cells, 1AR-GFP displayed identical ligand-binding isotherms and adenylyl cyclase activation as native 1AR. Upon exposure to isoproterenol, a fraction of 1AR-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 1AR-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 1AR-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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				B. Eisensamer, M. Uhr, S. Meyr, G. Gimpl, T. Deiml, G. Rammes, J. J. Lambert, W. Zieglgansberger, F. Holsboer, and R. Rupprecht Antidepressants and Antipsychotic Drugs Colocalize with 5-HT3 Receptors in Raft-Like Domains J. Neurosci., November 2, 2005; 25(44): 10198 - 10206. [Abstract] [Full Text] [PDF]

				S. Avissar, A. Matuzany-Ruban, K. Tzukert, and G. Schreiber {beta}-Arrestin-1 Levels: Reduced in Leukocytes of Patients With Depression and Elevated by Antidepressants in Rat Brain Am J Psychiatry, November 1, 2004; 161(11): 2066 - 2072. [Abstract] [Full Text] [PDF]