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

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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-beta-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.

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