PT  - JOURNAL ARTICLE
AU  - Baoyong Sun
AU  - Carol R. Sterling
AU  - A. William Tank
TI  - Chronic Nicotine Treatment Leads to Sustained Stimulation of Tyrosine Hydroxylase Gene Transcription Rate in Rat Adrenal Medulla
AID  - 10.1124/jpet.102.043596
DP  - 2003 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 575--588
VI  - 304
IP  - 2
4099  - http://jpet.aspetjournals.org/content/304/2/575.short
4100  - http://jpet.aspetjournals.org/content/304/2/575.full
SO  - J Pharmacol Exp Ther2003 Feb 01; 304
AB  - Nicotine is a powerful stimulant of the sympathoadrenal system, causing the release of peripheral catecholamines and activation of catecholamine biosynthesis. In previous reports, we have studied the mechanisms by which short-term nicotine treatment regulates tyrosine hydroxylase (TH) in adrenal medulla. In this report, we study the effects of chronic nicotine treatment on adrenal TH gene expression. Rats were injected with either saline or nicotine twice per day for up to 14 days. Chronic nicotine treatment elicited long-lasting, dose-dependent increases in the levels of adrenal TH mRNA, TH protein, and TH activity. In contrast, a single injection of nicotine elicited only a small increase in adrenal TH mRNA levels, which was transient and did not result in the induction of TH enzyme. Chronic nicotine administration also elicited a sustained increase in adrenal TH gene transcription rate, which persisted for up to 7 days after the final nicotine injection. This sustained transcriptional response correlated with a modest sustained increase in adrenal TH AP1 binding, but not in the levels of Fra-2 or other fos or jun proteins. These results demonstrate that repeated nicotine injections administered chronically over 1 to 2 weeks lead to sustained stimulation of the TH gene and consequent induction of TH gene expression in rat adrenal medulla. These studies support the hypothesis that chronic nicotine administration produces long-lasting cellular changes in adrenal medulla that lead to sustained transcriptional responses. The American Society for Pharmacology and Experimental Therapeutics