Inhibitors of cyclic-nucleotide phosphodiesterase induce morphological differentiation of mouse neuroblastoma cell culture

Abstract

Inhibitors of phosphodiesterase, papaverine, 4-(3-butoxy-4-methoxybenzyl)-2 imidazolidinone (RO 20-1724) and 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (RO-7-2956) induce morphological differentiation of mouse neuroblastoma cells in culture as shown by the formation of axon-like processes. These differentiated cells showed morphological maturation as revealed by an increase in the size of soma and nucleus. On removal of papaverine and re-addition of fresh growth medium 1 day after treatment, the morphological differentiation was reversible; however, when the drug was removed 3 days after treatment, the morphological differentiation for the most part was irreversible. Although a maximal differentiation of cells was seen 24 h after papaverine treatment, a maximal inhibition of cell division was observed 2 days after treatment. This observation further supports the hypothesis that the inhibition of cell division may be secondary to the induction of differentiation.