Vasoactive intestinal peptide suppresses neuronal cell death induced by nerve growth factor deprivation in rat sympathetic ganglion cells in vitro.

Neuropeptides were examined for their effects on the survival of cultured rat superior cervical ganglion cells after acute deprivation of nerve growth factor (NGF). Vasoactive intestinal peptide (VIP, 3 microM) delayed the neuronal death about 6 h alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mM) greatly potentiated its effect, reducing EC50 from 2.5 microM to 8 nM. The neuronal death was completely suppressed under this condition. On the other hand, substance P (1-100 microM) or enkephalin (1-100 microM) alone did not modify the death, whereas the latter (100 microM) enhanced the survival-promoting effect of membrane depolarization with elevated K+. These results suggest strongly that neuropeptides regulate the NGF-independent survival of sympathetic neurons through a cAMP-dependent mechanism.