Document Detail


Exocytic trafficking is required for nicotine-induced up-regulation of alpha 4 beta 2 nicotinic acetylcholine receptors.
MedLine Citation:
PMID:  15741168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The primary target for nicotine in the brain is the neuronal nicotinic acetylcholine receptor (nAChR). It has been well documented that nAChRs respond to chronic nicotine exposure by up-regulation of receptor numbers, which may underlie some aspects of nicotine addiction. In order to investigate the mechanism of nicotine-induced nAChR up-regulation, we have developed a cell culture system to assess membrane trafficking and nicotine-induced up-regulation of surface-expressed alpha(4)beta(2) nAChRs. Previous reports have implicated stabilization of the nAChRs at the plasma membrane as the potential mechanism of up-regulation. We have found that whereas nicotine exposure results in up-regulation of surface receptors in our system, it does not alter surface receptor internalization from the plasma membrane, postendocytic trafficking, or lysosomal degradation. Instead, we find that transport of nAChRs through the secretory pathway to the plasma membrane is required for nicotine-induced up-regulation of surface receptors. Therefore, nicotine appears to regulate surface receptor levels at a step prior to initial insertion in the plasma membrane rather than by altering their endocytic trafficking or degradation rates as had been previously suggested.
Authors:
Tamara Darsow; T K Booker; Juan Carlos Piña-Crespo; Stephen F Heinemann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-03-01
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-03     Completed Date:  2005-09-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18311-20     Citation Subset:  IM    
Affiliation:
Molecular Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. darsow@salk.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Exocytosis / drug effects,  physiology*
Humans
Mice
Nicotine / pharmacology*
Protein Transport / drug effects,  physiology
Receptors, Nicotinic / biosynthesis*
Up-Regulation / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
AA13018/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Nicotinic; 0/nicotinic receptor alpha4beta2; 54-11-5/Nicotine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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