Subtype-specific neuronal differentiation of PC12 cells transfected with α 2-adrenergic receptors

Cells of the PC12 rat pheochromocytoma cell line acquire characteristics of sympathetic neurons under appropriate treatment. Stably transfected PC12 cells expressing individual α 2-adrenergic receptor (α 2-AR) subtypes were used to assess the role of α 2-ARs in neuronal differentiation and to charac... Full description

Cells of the PC12 rat pheochromocytoma cell line acquire characteristics of sympathetic neurons under appropriate treatment. Stably transfected PC12 cells expressing individual α 2-adrenergic receptor (α 2-AR) subtypes were used to assess the role of α 2-ARs in neuronal differentiation and to characterise the signalling pathways activated by the α 2-AR agonist epinephrine in these cells. The effects of α 2-AR activation were compared with the differentiating action and the signalling mechanisms of nerve growth factor (NGF). Epinephrine induced neuronal differentiation of PC12α 2 cells through α 2-AR activation in a subtype-dependent manner, internalization of all human α 2-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 PC12α 2 subtype clones. Evaluation of the potential physiological consequences of these findings requires further studies on endogenously expressed α 2-ARs in neuronal cells.