Transcriptional and post-transcriptional regulation of noradrenaline transporter gene expression by nicotine

我们研究了尼古丁对大鼠嗜铬细胞瘤PC12细胞、人神经母细胞瘤SK-N-SH细胞和大鼠组织去甲肾上腺素转运体(NET)表达的影响。尼古丁对瞬时转染SK-N-SH和PC12细胞的人Net基因的转录活性没有影响。然而，尼古丁在几个小时内降低了SK-N-SH细胞的净mRNA水平。相反，尼古丁上调PC12细胞中Net的mRNA和蛋白。单次给予尼古丁可增加大鼠肾上腺髓质和脑干中的净信使核糖核酸水平，而慢性尼古丁治疗2周则降低了净信使核糖核酸的水平。这些结果表明尼古丁通过转录后机制上调和下调Net的表达。尼古丁引起的Net表达下降可能与尼古丁的药理作用有特殊的临床意义。

We investigated the effects of nicotine on noradrenaline transporter(NET) expression in PC12 cells derived from rat pheochromocytoma, human neuroblastoma SK-N-SH cells, and rat tissues. Nicotine had no influence on the transcriptional activity of human NET gene constructs transiently transfected in SK-N-SH and PC12 cells. However, nicotine decreased NET mRNA levels within several hours in SK-N-SH cells. In contrast, nicotine up-regulated the mRNA and protein of NET in PC12 cells. A single administration of nicotine increased NET mRNA levels in the adrenal medulla and brain stem of the rat, whereas chronic nicotine treatment for 2 weeks decreased NET mRNA levels. These results suggest that nicotine up- and down-regulates the expression of NET through a posttranscriptional mechanism. The decrease in NET expression induced by nicotine may be ofparticular clinical relevance to the pharmacological action of nicotine.