Mediation of serum-induced changes in cyclic nucleotide levels in cultured fibroblasts by cyclic nucleotide phosphodiesterase

Abstract

CELL cultures of untransformed fibroblasts can be maintained in a stationary or relatively quiescent state by adjusting serum concentrations to suboptimal levels1. Addition of excess serum to quiescent cell cultures causes a rapid decrease in the intracellular concentration of cyclic AMP and a rapid increase in cyclic GMP levels2–5. These alterations in cyclic nucleotide concentrations precede the changes in macromolecular synthesis (such as RNA, protein and DNA synthesis) and growth induced by serum, and constitute one of the earliest steps in the sequence of events before the initiation of growth. The mechanism responsible for altering cyclic nucleotide concentrations in response to serum or other growth stimuli has not been elucidated however. We show here that a rapid alteration in cyclic nucleotide phosphodiesterase activity occurs when serum is added to quiescent fibroblasts and demonstrate that this alteration could mediate the changes in cyclic nucleotide levels.