Exocytic Trafficking Is Required for Nicotine-induced Up-regulation of α4β2Nicotinic Acetylcholine Receptors

Tamara Darsow, T. K. Booker, Juan Carlos Piña-Crespo, Stephen F. Heinemann
2005 Journal of Biological Chemistry  
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 ␣ 4 ␤ 2 nAChRs.
more » ... 4 ␤ 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.
doi:10.1074/jbc.m501157200 pmid:15741168 fatcat:i6nbizmigbcipndn6uou6uv7ue