Nerve growth factor, epidermal growth factor, and insulin differentially potentiate ATP-induced [Ca2+]i rise and dopamine secretion in PC12 cells.
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.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
C M
CM
Huang
L S
LS
Kao
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects; D013268:Stimulation, Chemical; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D007328:Insulin; D008934:Mitogens; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D013729:Terpenes; D004815:Epidermal Growth Factor; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D004299:Dopamine beta-Hydroxylase; D011188:Potassium; D002118:Calcium; D004298:Dopamine