Nerve growth factor and K-252a increase catecholamine release from PC12 cells

PC12 cells are a nerve growth factor-responsive clone derived from a rat pheochromocytoma. The cells contain catecholamines and secrete them in response to depolarizing stimuli and cholinergic agonists. Treatment of the cells with nerve growth factor produces a number of very rapid changes, including the structural rearrangement of the cell membrane, the generation of a number of different second messengers, and the phosphorylation of several proteins. The present studies show that nerve growth factor treatment increases the release of dopamine and norepinephrine from the cells within a few minutes and does so independently of its effect on their metabolism. The experiments indicate that this effect on nerve growth factor is dependent on the presence of extracellular calcium and can be blocked by calcium channel antagonists. K-252a, an alkaloid-like material, usually found to inhibit the actions of nerve growth factor on PC12 cells, also increases the release of catecholamines under these conditions.