Responses to cAMP depend on stage of neuronal differentiation of NGF-treated adrenal chromaffin cells.

The nerve growth factor (NGF)-dependent transdifferentiation of adrenal chromaffin cells into sympathetic neurons occurs in two sequential phases: The first phase, in which cells extend neurites and increase proliferation, is mimicked by phorbol myristate acetate (PMA), an activator of protein kinase C. Analogs of cAMP, and forskolin, an activator of adenylate cyclase, antagonize the early effects of both NGF and PMA. The second phase of transdifferentiation, in which cells withdraw from the mitotic cycle and express a true neuronal phenotype, occurs after about 2 weeks of exposure to NGF and is neither mimicked by PMA alone nor antagonized by cAMP. Rather, cAMP promotes the neuronal phenotype of cells previously exposed to NGF or PMA. Thus NGF appears to activate different second messenger systems depending on the stage of differentiation of its target cells.