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    
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.
Tamara Darsow; T K Booker; Juan Carlos Piña-Crespo; Stephen F Heinemann
Related Documents :
12769608 - Recent progress in the development of subtype selective nicotinic acetylcholine recepto...
9681478 - D alpha3, a new functional alpha subunit of nicotinic acetylcholine receptors from dros...
3715468 - Acetylcholine receptor synthesis in retina and transport to optic tectum in goldfish.
21376468 - Leptin enhances nmda-induced spinal excitation in rats: a functional link between adipo...
1731778 - Characterization of heparin-binding growth-associated factor receptor on nih 3t3 cells.
22785548 - Expression of p2x1 and p2x4 receptors in rat trigeminal ganglion neurons.
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    
Molecular Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Line
Exocytosis / drug effects,  physiology*
Nicotine / pharmacology*
Protein Transport / drug effects,  physiology
Receptors, Nicotinic / biosynthesis*
Up-Regulation / drug effects,  physiology*
Grant Support
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

Previous Document:  Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junctio...
Next Document:  Functional analysis of active site residues of the fosfomycin resistance enzyme FosA from Pseudomona...