Increase in intracellular Ca2+ level and modulation of nerve growth factor action on pheochromocytoma PC12h cells by extracellular ATP.

Extracellular ATP increased the cytosolic Ca2+ level of pheochromocytoma PC12h cells, a subclonal line of PC12. This increase in Ca2+ was predominantly due to an increased Ca2+ influx rather than to intracellular mobilization of the ion. One half of the maximal increase in Ca2+ level was observed with an ATP concentration of approximately 1 microM. ADP also induced an increase in cytosolic Ca2+ but to a lesser extent than ATP, whereas neither AMP nor adenosine showed such effect. ATP also modulated the nerve growth factor (NGF) action on these cells: ATP enhanced the NGF-induced neurite outgrowth, although ATP alone did not cause neurite development. After 3-day treatment the average neurite length of the cells treated with both NGF and ATP was about 1.5-fold greater than that of the cells treated with NGF alone. ADP also showed similar effect as ATP, while AMP did not. The ATP concentration that gave one half of the maximal enhancement of the outgrowth was estimated to be 180 microM. Enhancement of NGF-induced neurite outgrowth by ATP was also observed in serum-free cultures. The enhancing effect on NGF-induced neurite outgrowth was also specific for ATP. These results thus indicate the presence and involvement of P2-type purinergic receptors on PC12h cells in the ATP effects, and suggest a novel function of extracellular ATP as a modulator of hormonal actions.