Cyclic AMP and pituitary adenylate cyclase-activating polypeptide (PACAP) prevent programmed cell death of cultured rat cerebellar granule cells.

Cultured cerebellar granule cells undergo programmed cell death when they are deprived of depolarizing KCl. Results from this study indicate that the cAMP analog cyclic 8-(4-chlorophenylthio) adenosine-3'5'-monophosphate (CPT-cAMP) can prevent the cell death in a dose-dependent manner, with the maximal effect seen at 500 microM. Approximately 70% of cells can be saved with this concentration of CPT-cAMP for at least 6 days. Pituitary adenylate cyclase-activating polypeptide (PACAP) increased the intracellular cAMP levels of these cells in a time- and dose-dependent manner. This agent can prevent the decrease of cAMP and cell death induced by KCl withdrawal. These results suggest that PACAP could function as a neurotrophic factor for cerebellar granule cells in vivo.