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 mu M) delayed the neuronal death about 6 h alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mM) greatly potentiated its effect, reducing EC(50) from 2.5 mu M to 8 nM. The neuronal death was completely suppressed under this condition. On the other hand, substance P (1-100 mu M) or enkephalin (1-100 mu M) alone did not modify the death, whereas the latter (100 mu M) 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.