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- W2055762844 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." @default.
- W2055762844 created "2016-06-24" @default.
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- W2055762844 date "2005-06-08" @default.
- W2055762844 modified "2023-09-25" @default.
- W2055762844 title "Chronic Nicotine Exposure Upregulates Nicotinic Receptors by a Novel Mechanism" @default.
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- W2055762844 doi "https://doi.org/10.1523/jneurosci.5240-04.2005" @default.
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