Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Abstract

The effects of serum deprivation on several general cellular biochemical processes ("pleiotypic response") related to the growth of normal fibroblasts can be mimicked by treatment of these cells with prostaglandin E(1) in the presence of serum. N(6),O(2)'-Dibutyryl adenosine 3':5'-cyclic monophosphate and theophylline inhibit the membrane transport processes without much effect on other pleiotypic reactions such as overall protein and RNA synthesis and protein degradation. The amount of intracellular cyclic AMP increases during serum starvation and returns to the initial concentration in unstarved cells when growth is initiated again upon addition of serum. Fibroblasts transformed by simian virus 40 have a lower cyclic AMP content than their untransformed parents. Serum deprivation neither increases cyclic AMP content nor significantly affects the pleiotypic reactions in transformed cells. Cycloheximide causes a decrease in cyclic AMP content of normal fibroblasts coincidentally with the ability of this inhibitor to stimulate uridine transport and slow protein degradation in cells deprived of serum.