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

我们研究了尼古丁对来自大鼠嗜铬细胞瘤、人神经母细胞瘤SK-N-SH细胞和大鼠组织的PC 12细胞中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PC 12细胞的人NET基因构建体的转录活性没有影响。然而，尼古丁在SK-N-SH细胞中在数小时内降低NET mRNA水平。相反，尼古丁上调PC 12细胞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NET mRNA水平，而持续2周的慢性尼古丁治疗可降低NET mRNA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。尼古丁诱导的NET表达减少可能与尼古丁的药理作用具有特殊的临床相关性。

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.