Effects of short- and long-term nicotine treatment on intracellular calcium and tyrosine hydroxylase gene expression.

: It is important to determine how the signaling pathways for the short-term effects of nicotine (catecholamine secretion, phosphorylation of tyrosine hydroxylase) differ from those required for changes in gene expression. Our aim was to distinguish the pathways involved in short- and long-term nicotinic stimulation. PC12 cells were treated with several concentrations of nicotine from 10 μM to 1 mM. All elicited a rapid and transient rise in [Ca2+]i, which was concentration dependent. After several minutes of continued exposure, a second smaller sustained rise in [Ca2+]i was only observed with intermediate concentrations of nicotine (50-200 μM). This sustained rise was not observed in cells pretreated with α-bungarotoxin (α-BTX). α-BTX also prevented the elevation of tyrosine hydroxylase mRNA by nicotine. The effects of brief and prolonged treatment with nicotine on the signaling pathways involved in changes in [Ca2+]i and induction of tyrosine hydroxylase gene expression are summarized. The results indicate that nicotine may elicit different signaling pathways depending on the concentration. The sustained elevation of [Ca2+]i via activation of α7 nAChRs is proposed as the mechanism leading to increased tyrosine hydroxylase gene expression.