Cyclic 3′,5′-AMP Phosphodiesterase Activity During Cyclic AMP-Induced Differentiation of Neuroblastoma Cells in Culture 1

Abstract

Summary

The cyclic AMP phosphodiesterase (PDE) activity markedly increased in morphologically “differentiated” mouse neuroblastoma cells induced by dibutyryl cyclic AMP, prostaglandin E₁ (stimulator of adenylate cyclase) and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724, an inhibitor of PDE). Initially, RO 20-1724 decreased the PDE activity by about 50% of control, but later it increased the PDE activity. All of the above agents are known to increase the endogenous level of cyclic AMP, and therefore, in the differentiated cells, a high level of PDE correlated well with a high level of cyclic AMP. X-Irradiation which causes morphological “differentiation” similar to that by dibutyryl cyclic AMP did not increase the PDE activity. Sodium butyrate, 3′,5′-cyclic AMP, 5′-AMP and theophylline which inhibit cell division without causing morphological differentiation did not affect significantly the basal level of PDE. Cycloheximide markedly reduced the PDE activity, whereas actinomycin D did not. A working hypothesis is proposed that during “differentiation” of neuroblastoma cells in culture the levels of both cyclic AMP and PDE increase, the former probably due to an increase in adenylate cyclase; a reverse process may occur during malignant transformation of nervous tissues.