Kinetics of regulation of neurotensin content in PC12 cells

The mechanism by which nerve growth factor (NGF) and dexamethasone synergistically increase the content of neurotensin (NT) in PC12 cells can be partially separated into NGF and dexamethasone-mediated components by study of cultures pre-treated with either agent. The detectable early response of NGF-treated cells to dexamethasone is at least 24 hours faster than that of dexamethasone-treated cells to NGF, and is also greater in both absolute and relative magnitude. Both in NGF-treated cultures exposed to dexamethasone and in dexamethasone-treated cultures exposed to NGF, however, the rates of increase in NT content are initially low and then accelerate, suggesting periods of enzyme induction preceding NT accumulation. This suggestion is further supported by the absence of increases in the presence of actinomycin D, but an apparently paradoxical increase in NT content is observed in the presence of camptothecin. The findings are consistent with a complex interaction between NGF and dexamethasone, which might involve induction of multiple enzymes.