期刊
JOURNAL OF NEUROCHEMISTRY
卷 104, 期 2, 页码 446-456出版社
WILEY
DOI: 10.1111/j.1471-4159.2007.05011.x
关键词
nicotine; nicotinic receptor; regulation; subunit composition; alpha 5 nicotinic subunit
资金
- NIDA NIH HHS [DA015767, R01 DA015767, DA12976] Funding Source: Medline
- NATIONAL INSTITUTE ON DRUG ABUSE [R56DA012976, R01DA015767, R01DA012976] Funding Source: NIH RePORTER
We used immunoprecipitation with subunit-specific antibodies to examine the distribution of heteromeric neuronal nicotinic acetylcholine receptors (nAChRs) that contain the alpha 5 subunit in the adult rat brain. Among the regions of brain we surveyed, the alpha 5 subunit is associated in similar to 37% of the nAChRs in the hippocampus, similar to 24% of the nAChRs in striatum, and 11-16% of the receptors in the cerebral cortex, thalamus, and superior colliculus. Sequential immunoprecipitation assays demonstrate that the alpha 5 subunit is associated with alpha 4 beta 2* nAChRs exclusively. Importantly, in contrast to alpha 4 beta 2 nAChRs, which are increased by 37-85% after chronic administration of nicotine, the alpha 4 beta 2 alpha 5 receptors are not increased by nicotine treatment. These data thus indicate that the alpha 4 beta 2 alpha 5 nAChRs in rat brain are resistant to up-regulation by nicotine in vivo, which suggests an important regulatory role for the alpha 5 subunit. To the extent that nicotine-induced up-regulation of alpha 4 beta 2 nAChRs is involved in nicotine addiction, the resistance of the alpha 4 beta 2 alpha 5 subtype to up-regulation may have important implications for nicotine addiction.
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