NICOTINE REGULATES MESSENGER-RNA 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 examin ed the mRNA level of the tyrosine hydroxylase (TH) gene and that of th e nicotinic acetylcholine receptor (nAChR) genes by long-term nicotine treatment. The transcript levels of the four subunit genes of the nAC hR (alpha 3, alpha 5, alpha 7, and beta 4) were down-regulated by the treatment with forskolin, whereas the mRNA levels of the TH gene was i ncreased in PC12 cells. By long-term nicotine treatment, the mRNA leve l of the nAChR genes did not change, but transcript levels of alpha 3, alpha 5, alpha 7, and beta 4 nAChR genes were still negatively regula ted by forskolin. However, the mRNA level of TH gene did not change by forskolin under long-term nicotine treatment. The TH gene may be regu lated by a nicotine-related signaling pathway, whereas alpha 3, alpha 5, alpha 7, and beta 4 nAChR genes may be further regulated by a prote in kinase A (PKA) pathway under long-term nicotine treatment. (C) 1997 Elsevier Science Ireland Ltd.