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 t hey are deprived of depolarizing KCl. Results from this study indicate that the cAMP analog cyclic 8-(4-chlorophenylthio) adenosine-3'5'-mon ophosphate (CPT-cAMP) can prevent the cell death in a dose-dependent m anner, with the maximal effect seen at 500 mu M. Approximately 70% of cells can be saved with this concentration of CPT-cAMP for at least 6 days. Pituitary adenylate cyclase-activating polypeptide (PACAP) incre ased 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 cou ld function as a neurotrophic factor for cerebellar granule cells in v ivo.