Ishiguro H, Ichino N, Yamada K, Nagatsu T
Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Neurosci Lett. 1997 May 30;228(1):37-40. doi: 10.1016/s0304-3940(97)00360-1.
To understand the molecular mechanism of nicotine addiction, we examined the mRNA level of the tyrosine hydroxylase (TH) gene and that of the nicotinic acetylcholine receptor (nAChR) genes by long-term nicotine treatment. The transcript levels of the four subunit genes of the nAChR (alpha3, alpha5, alpha7, and beta4) were down-regulated by the treatment with forskolin, whereas the mRNA levels of the TH gene was increased in PC12 cells. By long-term nicotine treatment, the mRNA level of the nAChR genes did not change, but transcript levels of alpha3, alpha5, alpha7, and beta4 nAChR genes were still negatively regulated by forskolin. However, the mRNA level of TH gene did not change by forskolin under long-term nicotine treatment. The TH gene may be regulated by a nicotine-related signaling pathway, whereas alpha3, alpha5, alpha7, and beta4 nAChR genes may be further regulated by a protein kinase A (PKA) pathway under long-term nicotine treatment.
为了解尼古丁成瘾的分子机制，我们通过长期尼古丁处理检测了酪氨酸羟化酶（TH）基因和烟碱型乙酰胆碱受体（nAChR）基因的mRNA水平。用福司可林处理后，nAChR的四个亚基基因（α3、α5、α7和β4）的转录水平下调，而在PC12细胞中TH基因的mRNA水平升高。通过长期尼古丁处理，nAChR基因的mRNA水平没有变化，但α3、α5、α7和β4 nAChR基因的转录水平仍受到福司可林的负调控。然而，在长期尼古丁处理下，福司可林并未改变TH基因的mRNA水平。TH基因可能受尼古丁相关信号通路调控，而在长期尼古丁处理下，α3、α5、α7和β4 nAChR基因可能进一步受蛋白激酶A（PKA）通路调控。
