Cooperative regulation of neurotensin content in PC12 pheochromocytoma cell cultures: effects of nerve growth factor, dexamethasone, and activators of adenylate cyclase.

Nerve growth factor, dexamethasone, and forskolin or cholera toxin (CT) act cooperatively to increase the content of neurotensin (NT) in PC12 pheochromocytoma cells. Relatively small increases in NT content occur in the presence of NGF alone or dexamethasone alone, but not of forskolin or CT alone. Increases of 10- to 100-fold occur in the presence of NGF plus dexamethasone or NGF plus forskolin, and up to 600-fold increases occur in the presence of all three agents. These increases are extremely stable and persist for at least 2 weeks after removal of dexamethasone or forskolin. The complex regulation of NT stores in PC12 cells might reflect mechanisms that regulate NT content of normal chromaffin cells and/or neurons during development or in adult life. A small amount of stored NT is released in response to stimulation with 52 mM K+. This release is blocked in the presence of 2 mM Co2+, suggesting that it occurs via Ca2+-mediated exocytosis.