Letter | Published:

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



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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Temin, H. M., Pierson, R. W., and Dulab, N. C., in Growth, Nutrition and Metabolism of Cells in Culture (edit. by Rothblat, G. H., and Cristofals, V. J.), 50–82 (Academic London, 1972).

  2. 2

    Sheppard, J. R., Nature new Biol., 236, 14–16 (1972).

  3. 3

    Seifert, W., and Paul, D., Nature new Biol., 240, 281–283 (1972).

  4. 4

    Seifert, W. E., and Rudland, P. S., Nature, 248, 138–140 (1974).

  5. 5

    Rudland, P. S., Seeley, M., and Seifert, W., Nature, 251, 417–419 (1974).

  6. 6

    Lineweaver, H., and Burk, D., J. Am. chem. Soc., 56, 658–666 (1934).

  7. 7

    Schröder, J., and Plagemann, P. G. W., J. natn. Cancer Inst., 46, 423–429 (1971).

  8. 8

    Pledger, W. J., Thompson, W. J., and Strada, S. J., J. Cyclic Nucl. Res. (in the press).

  9. 9

    Thompson, W. J., and Appleman, M. M., Biochemistry, 10, 311–316 (1971).

  10. 10

    Thompson, W. J., and Appleman, M. M., J. biol. Chem., 246, 3145–3150 (1971).

  11. 11

    Steiner, A. L., Parker, C. W., and Kipnis, D. M., J. biol. Chem., 247, 1106–1113 (1972).

  12. 12

    Thompson, W. J., and Williams, R. H., Archs biochem. Biophys., 165, 468–477 (1974).

Download references

Author information

Rights and permissions

To obtain permission to re-use content from this article visit RightsLink.

About this article

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.