Search Here

Tobacco is responsible for the greatest number of preventable deaths worldwide by any single agent. New research reveals that nicotine, the active ingredient in tobacco, exploits the body's cellular machinery to promote addiction.

New research reveals that nicotine stimulates receptors known as nAChRs and acts as a "pharmacological chaperone" to stabilize assembly of its receptors within the Endoplasmic Reticulum (ER) and increase their abundance at the cell surface (up-regulation). Researchers note that up-regulation of nAChRs is partly responsible for nicotine addiction and lower risk of Parkinson's disease in smokers.

The findings revealed that receptors containing an ∝6 subunit (∝6* nAChRs) are abundant in several specific brain regions. They found that mice expressing ∝6 labeled with a fluorescent protein to show nicotine exposure-at a level comparable to that in human smokers-up-regulated ∝6* nAChRs in these areas of the brain.

Surprisingly, researchers at the California Institute of Technology in Pasadena also found that nicotine's ability to up-regulate ∝6* nAChRs relied on the retrograde transport of ∝6* nAChRs back from the Golgi to the ER by COPI-coated vesicles.

Golgi-ER cycling (involving COPI vesicles) may be a common mechanism for up-regulation of other nAChRs by nicotine, according to researchers. They said that manipulation of this process could lead to new therapies to help people quit smoking and offer neuroprotection against Parkinson's disease.  

The findings are published in The Journal of General Physiology.