Cyclic GMP and cyclic AMP levels in normal and transformed fibroblasts.

Abstract

THE 3′–5′ cyclic nucleotides, cyclic AMP and cyclic GMP have been implicated in the control of the growth of cultured fibroblasts in that early, transient decreases in intracellular cyclic AMP1–3 and increases in cyclic GMP4 are observed on reinitiation of the growth of quiescent mouse fibroblasts by serum. Moreover additions of high, nonphysiological concentrations (10−5 M to 10−3 M) of either cyclic AMP or cyclic GMP (or their butyrated analogues) either suppress the induction of DNA synthesis after serum addition5 or initiate substantial increases in DNA synthesis respectively4 in quiescent mouse fibroblasts. Cyclic nucleotide concentrations in asynchronously-growing cell cultures are an average over the entire cell cycle and depend for cyclic AMP on the proportion of cells in a particular phase. The average cyclic AMP level is often correlated with growth rate6, although this may not be such a reliable parameter for cell growth as the relative proportions of G1, S, G2 and M vary with cell type and the culture conditions7. The larger changes in cyclic GMP are correlated directly with the initiation of fibroblast growth when cells are moving out of the G0 state or by passage through the M and G1 boundary and are not exhibited during the remainder of the cell cycle (W. S., and P. S. R., unpublished). Thus cyclic GMP concentrations and the ratios of cyclic AMP to cyclic GMP may be more sensitive and reliable indicators of the growth state of a cell.