News From The Journal Of Biological Chemistry

Main Category: Biology / Biochemistry
Also Included In: Alcohol / Addiction / Illegal Drugs;  Smoking / Quit Smoking;  Neurology / Neuroscience
Article Date: 03 Mar 2008 - 2:00 PDT

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Nicotine's Effects are Receptor Specific

Following chronic nicotine exposure, nicotine receptors increase in number, an upregulation that contributes to nicotine's addictive properties. While a current belief is that this process is independent of the type of nicotine receptor, researchers have now uncovered this is not the case: the transient and prolonged changes in the nicotine levels of smokers each affect a specific receptor subtype.

The predominant subtype of nicotine receptor in the brain is known as A4B2; these receptors upregulate as nicotine levels gradually rise in the blood. Generally, they start increasing about 2-3 hours following exposure and peak after about 20 hours.

Due to lower prevalance, the upregulation, if any, of minor nicotine receptor subtypes has been difficult, but William Green and colleagues successfully developed cells expressing A6B2 nicotine receptors. They then demonstrated this class also undergoes nicotine upregulation, but at a much faster rate; A6B2 receptors increase within minutes of exposure and peak after only 2 hours.

These receptors also required about 10 times as much nicotine to stimulate as A4B2 receptors, a level that would only be reached during the brief spikes in nicotine levels occurring during smoking. These results offer new insights into the different phases of smoking, highlighting that separate receptors modulate the immediate and long term effects of nicotine.

Corresponding Authors: William Green, Department of Neurobiology, University of Chicago, Illinois

Two-protein Complex Protects Nerve Cells

Since its discovery as a protein that gets specifically released in response to brain injury, ciliary neurotrophic factor (CNTF) has prompted much interest as a potential therapeutic agent. However, numerous experiments have met with limited success, until now; a research team shows that co-administrating CNTF with its receptor promotes the growth and survival of neurons.

While the receptor for CNTF is normally tied to the surface of neurons, this tether is frequently chopped off during trauma, which led Mark Ozog, Christian Naus and colleagues to suspect that CNTF and the free-floating receptor might act in a complex.

They treated mouse neurons with CNTF, its receptor (CNTFR), or both and then exposed the cells to massive amounts of the neurotransmitter glutamate, enough to kill the neurons by over-stimulating them. CNTF or CNTFR alone did not protect the neurons, but the two complexed together could. In addition, the complex could foster increased growth of nerve cells.

Ozog, Naus and colleagues next ran a microarray analysis of the CNTF complex and found that it altered the expression of 47 genes associated with nerve growth and survival, suggesting it protects neurons through multiple direct and indirect mechanisms and thus making it a strong therapeutic candidate.

Corresponding Author: Christian Naus, Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, CA

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The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society's Web site at http://www.asbmb.org/.

Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology

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