Year: 2005
Type: article
Abstract: Nicotine addiction is initiated by its binding to high-affinity nicotinic receptors in brain composed primarily of alpha4 and beta2 subunits. For nicotinic receptors expressed in vivo or heterologously, nicotine exposure over hours to days increases or "upregulates" high-affinity nicotine binding to receptors through a posttranslational mechanism thought to increase receptor numbers. Using heterologous expression, we find nicotine exposure causes a fourfold to sixfold higher binding to alpha4beta2 receptors that does not correspond with any significant change in the number of surface receptors or a change in the assembly, trafficking, or cell-surface turnover of the receptors. However, upregulation does alter the functional state of the receptor, slowing desensitization and enhancing sensitivity to acetylcholine. Based on these findings, we propose an alternative mechanism to explain nicotine-induced upregulation in which nicotine exposure slowly stabilizes alpha4beta2 receptors in a high-affinity state that is more easily activated, thereby providing a memory for nicotine exposure.
Source: Journal of Neuroscience
Author: Y. F. Vallejo
Institution: University of Chicago
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Award: G4717498501
OpenAlex ID: W2055762844