Sabban Esther L, Gueorguiev Volodia D
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
Ann N Y Acad Sci. 2002 Oct;971:39-44. doi: 10.1111/j.1749-6632.2002.tb04430.x.
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 micro M to 1 mM. All elicited a rapid and transient rise in Ca(2+), which was concentration dependent. After several minutes of continued exposure, a second smaller sustained rise in Ca(2+) was only observed with intermediate concentrations of nicotine (50-200 micro M). This sustained rise was not observed in cells pretreated with alpha-bungarotoxin (alpha-BTX). alpha-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 Ca(2+) 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 Ca(2+) via activation of alpha7 nAChRs is proposed as the mechanism leading to increased tyrosine hydroxylase gene expression.
确定尼古丁短期效应（儿茶酚胺分泌、酪氨酸羟化酶磷酸化）的信号通路与基因表达变化所需的信号通路有何不同很重要。我们的目的是区分短期和长期烟碱刺激所涉及的信号通路。用10微摩尔至1毫摩尔的几种浓度的尼古丁处理PC12细胞。所有处理均引发细胞内钙离子浓度（Ca(2+)）迅速且短暂的升高，且呈浓度依赖性。持续暴露几分钟后，仅在中等浓度的尼古丁（50 - 200微摩尔）处理下观察到细胞内钙离子浓度第二次较小幅度的持续升高。在用α - 银环蛇毒素（α - BTX）预处理的细胞中未观察到这种持续升高。α - BTX还可阻止尼古丁诱导的酪氨酸羟化酶mRNA升高。总结了尼古丁短期和长期处理对细胞内钙离子浓度变化及酪氨酸羟化酶基因表达诱导所涉及的信号通路的影响。结果表明，尼古丁可能根据浓度引发不同的信号通路。通过激活α7烟碱型乙酰胆碱受体导致细胞内钙离子浓度持续升高被认为是酪氨酸羟化酶基因表达增加的机制。
