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 preventable deaths worldwide by any single agent. Nicotine, the active ingredient 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 nicotine addiction 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.
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Explore further: Carriers of a genetic mutation show increased dependence on tobacco
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
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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 preventable deaths worldwide by any single agent. Nicotine, the active ingredient 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 nicotine addiction 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.
Explore further: Carriers of a genetic mutation show increased dependence on tobacco
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
Medical Xpress on facebook
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Scientists reveal key mechanism governing nicotine addiction
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Scientists from the Florida campus of The Scripps Research Institute have identified a pathway in the brain that regulates an individual's vulnerability to the addictive properties of nicotine. The findings suggest a new ...
Carriers of a genetic mutation show increased dependence on tobacco
Dec 20, 2013
Scientists at the Institut Pasteur, the French National Center for Scientific Research (CNRS) and Pierre and Marie Curie University (UPMC) have recently proven that, in mice, nicotine intake– nicotine is the main addictive ...
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Nov 14, 2013
Nicotine withdrawal might take over your body, but it doesn't take over your brain. The symptoms of nicotine withdrawal are driven by a very specific group of neurons within a very specific brain region, according to a report ...
Study documents secondhand exposure to vapors from electronic cigarettes
Dec 13, 2013
Electronic cigarettes, when used indoors, may involuntarily expose non-users to nicotine, according to a study led by Maciej Goniewicz, PhD, PharmD, of Roswell Park Cancer Institute (RPCI) and published by the journal Nicotine an ...
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In preclinical studies, researchers at SRI International and Astraea Therapeutics have recently evaluated the role of a new drug receptor target that shows promise for the treatment of drug addiction.
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Dec 27, 2013
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