Nicotine regulates mRNA level of tyrosine hydroxylase gene but not that of nicotinic acetylcholine receptor genes in PC12 cells.

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.