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Cyclic AMP and pituitary adenylate cyclase-activating polypeptide (PACAP) prevent programmed cell death of cultured
J Y Chang1, V V Korolev, J Z Wang
1Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Abstract:
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.