Cyclic AMP Oscillations

Science's STKE  24 Jan 2006:
Vol. 2006, Issue 319, pp. tw37
DOI: 10.1126/stke.3192006tw37

The original second messenger, cyclic adenosine monophosphate (cAMP), has received a lot of attention but still has some new secrets to be revealed. Dyachok et al. provide evidence that oscillations in the concentration of intracellular cAMP occur and may result in distinct signals from those elicited by more stable increases in the amount of the second messenger. As every good student of signal transduction knows, when cAMP binds to the regulatory subunit of cAMP-dependent protein kinase, it causes dissociation of the catalytic and regulatory subunits. By tagging a truncated form of the regulatory subunit of cAMP-dependent protein kinase with a fluorescent label and expressing it in cells along with a fluorescently labeled version of the catalytic subunit, the authors could monitor rapid changes in the [cAMP]i as changes in fluorescence in live cells. In cultured rat insulinoma cells, GLP-1 (glucagon-like peptide 1) or glucagon at high doses produced stable increases in the [cAMP]i. However, lower doses caused oscillations in [cAMP]i with frequencies of .16 to 1.5 min–1 in 20 to 40% of the cells tested. The authors used stable or pulsatile application of a phosphodiesterase inhibitor (which blocks degradation of cAMP) to cause stable or oscillating changes in [cAMP]i and found that either treatment caused oscillations in the intracellular concentration of free calcium. However, only stable increases in [cAMP]i cause translocation of a fluorescently tagged version of the catalytic subunit of cAMP-dependent protein kinase to the nucleus. Thus, the authors propose that information may be encoded in the temporal pattern of cAMP signals as well as the absolute amount of the second messenger.

O. Dyachok, Y. Isakov, J. Sågetorp, A. Tengholm, Oscillations of cyclic AMP in hormone-stimulated insulin-secreting β-cells. Nature 439, 349-352 (2006). [PubMed]