Cells of the PC12 rat pheochromocytoma cell line acquire characteristics of sympathetic neurons under appropriate treatment. Stably transfected PC12 cells expressing individual alpha2-adrenergic receptor (alpha2-AR) subtypes were used to assess the role of alpha2-ARs in neuronal differentiation and to characterise the signalling pathways activated by the alpha2-AR agonist epinephrine in these cells. The effects of alpha2-AR activation were compared with the differentiating action and the signalling mechanisms of nerve growth factor (NGF). Epinephrine induced neuronal differentiation of PC12alpha2 cells through alpha2-AR activation in a subtype-dependent manner, internalization of all human alpha2-AR subtypes, and activation of mitogen-activated protein kinase (MAPK) and the serine-threonine protein kinase Akt. Epinephrine and NGF showed synergism in their differentiating effects. The MAPK kinase (MEK-1) inhibitor PD 98059 abolished the differentiating effect of epinephrine indicating that the differentiation is dependent on MAPK activation. Activating protein-1 (AP-1) DNA-binding activity was increased after epinephrine treatment in all three PC12alpha2 subtype clones. Evaluation of the potential physiological consequences of these findings requires further studies on endogenously expressed alpha2-ARs in neuronal cells.

中文翻译：

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转染了α2-肾上腺素受体的PC12细胞的亚型特异性神经元分化。

适当处理后，PC12大鼠嗜铬细胞瘤细胞系的细胞获得了交感神经元的特征。表达个别α2-肾上腺素受体（α2-AR）亚型的稳定转染的PC12细胞用于评估α2-AR在神经元分化中的作用，并表征这些细胞中由α2-AR激动剂肾上腺素激活的信号通路。将alpha2-AR激活的作用与神经生长因子（NGF）的分化作用和信号传导机制进行了比较。肾上腺素通过α2-AR激活以亚型依赖性方式，所有人类α2-AR亚型内在化以及丝裂原激活的蛋白激酶（MAPK）和丝氨酸-苏氨酸蛋白激酶Akt的激活，诱导PC12alpha2细胞的神经元分化。肾上腺素和NGF在区分作用上显示出协同作用。MAPK激酶（MEK-1）抑制剂PD 98059取消了肾上腺素的分化作用，表明该分化取决于MAPK激活。肾上腺素治疗后，在所有三个PC12alpha2亚型克隆中，激活蛋白1（AP-1）DNA结合活性均增加。对这些发现的潜在生理后果的评估需要对神经元细胞中内源表达的α2-AR进行进一步的研究。