Cyclic AMP and sympathetic neuronal programmed cell death.

The survival and proper functioning of sympathetic neurons are dependent on nerve growth factor (NGF). When immature sympathetic neurons are deprived of NGF, they undergo an 'active' dying process usually termed 'programmed cell death' or 'apoptosis'. This trophic factor dependence is age-related such that the cells become less dependent on NGF as they mature. Removal of NGF in immature cultures, which triggered the process of programmed cell death, resulted in a significant decrease of intracellular cAMP levels. In contrast, when these cells matured in culture and became relatively NGF independent, NGF withdrawal did not lead to a drop of cAMP levels. Pituitary adenylate cyclase-activating polypeptide (PACAP), a naturally occurring bioactive peptide structurally similar to VIP, could increase cAMP levels in these sympathetic neurons, and delay neuronal cell death resulting from NGF deprivation. These results suggest that PACAP may serve as a neurotrophic factor in sympathetic neurons.