Nicotine exploits COPI to foster addiction

December 30, 2013
Chronic exposure to nicotine (bottom image) up-regulates fluorescently labeled receptors known as nACHRs (green) in the substantia nigra pars compacta (SNc) and ventral tegmental (VTA) areas of the mouse brain. Up-regulation of nAChRs plays a major role in nicotine addiction and, possibly, in the decreased susceptibility of smokers to Parkinson's disease. Credit: Henderson et al., 2014

A study in The Journal of General Physiology helps explain how nicotine exploits the body's cellular machinery to promote addiction. The findings could lead to new therapies to help people quit smoking.

According to the Center for Disease Control and Prevention, tobacco accounts for the greatest number of worldwide by any single agent. Nicotine, the of tobacco, activates receptors known as nAChRs and, remarkably, unlike most other drugs of abuse, it 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). Up-regulation of nAChRs plays a major role in and, possibly, in the decreased susceptibility of smokers to Parkinson's disease.

Receptors containing an ∝6 subunit (∝6* nAChRs) are abundant in several specific brain regions. Researchers from the California Institute of Technology in Pasadena used mice expressing ∝6 labeled with a fluorescent protein to show that exposure to nicotine—at a level comparable to that in human smokers—up-regulated ∝6* nAChRs in these areas of the brain.

Unexpectedly, the researchers discovered 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. The authors believe that Golgi–ER cycling (involving COPI vesicles) may be a common mechanism for up-regulation of other nAChRs by nicotine. Manipulation of this process could therefore help form new strategies for smoking cessation and neuroprotection against Parkinson's disease.

This video is not supported by your browser at this time.
This video animation shows how nicotine acts as a chaperone for receptors called nAChRs in neurons, promoting their exit from the ER and eventually increasing their abundance at the plasma membrane. Nicotine-mediated activation of nAChRs also depends on the COPI machinery involved in Golgi–ER transport of nAChRs. The findings could help form new strategies for smoking cessation and neuroprotection against Parkinson's disease. Credit: Mary O'Reilly, O'Reilly Science Art

Explore further: Collaborative preclinical efficacy studies suggest a new target for drug addiction treatment

More information: Henderson, B.J., et al. 2014. J. Gen. Physiol. DOI: 10.1085/jgp.201311102
Anand, R. 2014. J. Gen. Physiol. DOI: 10.1085/jgp.201311136

Related Stories

Want to stop smoking? See a specialist

December 20, 2013

Smokers in England who want to stop smoking are three times more likely to succeed if they see a trained advisor than if they try by themselves, according to a new study published online today in the medical journal Addiction. ...

Recommended for you

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.