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Nerve Growth Factor, Epidermal Growth Factor, and Insulin Differentially Potentiate ATP‐Induced [Ca2+]i Rise and Dopamine Secretion in PC12 Cells

Abstract: To study how growth factors affect stimulus‐secretion coupling pathways, we examined the effects of nerve growth factor (NGF), epidermal growth factor (EGF), and insulin on ATP‐induced [Ca2+]i rise and dopamine secretion in PC12 cells. After a 4‐day incubation of cells, all three factors increased ATP‐induced dopamine secretion significantly. We then examined which step of ATP‐induced secretion was affected by the growth factors. Cellular levels of dopamine‐β‐hydroxylase and catecholamines were increased by NGF treatment but were not affected by EGF or insulin. The ATP‐induced [Ca2+]i rise was also enhanced after growth factor treatment. The EC50 of ATP for inducing [Ca2+]i rise and dopamine secretion was increased by NGF treatment but not by treatment with EGF or insulin. Accordingly, the dependence on [Ca2+]i of dopamine secretion was increased significantly only in NGF‐treated cells. Our results suggest that for EGF‐ and insulin‐treated PC12 cells, the increase in secretion is mainly due to increased potency of ATP in inducing [Ca2+]i rise. NGF treatment not only increased the potency of ATP but also decreased the Ca2+ sensitivity of the secretory pathway, which as a result becomes more tightly regulated by changes in [Ca2+]i.