Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

A Second Role for Second Messengers: Uncovering the Utility of Cyclic Nucleotide Hydrolysis

Abstract

A new technology based on enzyme-catalyzed incorporation of 18O from [18O]water into nucleotide phosphoryls is described that provides the capability to monitor the dynamics of cyclic AMP and cyclic GMP metabolism as well as the metabolism of high energy phosphates in intact cells. This 18O-labeling approach has provided evidence that cyclic GMP hydrolysis, tightly coupled to its synthesis, and independent of changes in cyclic nucleotide steady state levels, may represent a biochemical event of functional utility in its own right, and an essential biochemical event in phototransduction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Robison, G.A., Butcher, R.W. and Sutherland, E.W., 1971. Cyclic AMP. Academic Press, New York.

    Google Scholar 

  2. Goldberg, N.D. and Haddox, M.K. 1977. Cyclic GMP metabolism and involvement in biological regulation. Annu. Rev. Biochem. 46: 823–896.

    Article  CAS  Google Scholar 

  3. Greengard, P., Hayaishi, O. and Colowick, S.P. 1969. Enzymatic adenylation of pyrophosphate by 3′,5′ cyclic AMP: Reversal of the adenyl cyclase reaction. Fed. Proc. 28: 467.

    Google Scholar 

  4. Goldberg, N.D., Walseth, T.F., Stephenson, J.H., Krick, T.P. and Graff, G. 1980. l8O-Labeling of guanosine monophosphate upon hydrolysis of cyclic guanosine 3′:5′-monophosphate by phosphodiesterase. J. Biol. Chem. 255: 10344–10347.

    CAS  PubMed  Google Scholar 

  5. Walseth, T.F., Graff, G., Krick, T.P. and Goldberg, N.D. 1981. The fate of 18O in guanosine monophosphate during enzymic transformations leading to guanosine-3′:5′-cyclic monophosphate generation. J. Biol. Chem. 256: 2176–2179.

    CAS  PubMed  Google Scholar 

  6. Walseth, T.F., Gander, J.E., Eide, S.J., Krick, T.P. and Goldberg, N.D. 1983. 18O Labeling of adenine nucleotide alpha-phosphoryls in platelets: contribution of phosphodiesterase-catalyzed hydrolysis of cAMP. J. Biol. Chem. 258: 1544–1558.

    CAS  PubMed  Google Scholar 

  7. Fung, B.K.-K. and Stryer, L. 1980. Photolyzed rhodopsin catalyzes the exchange of GTP for bound GTP in retinal rod outer segments. Proc. Natl. Acad. Sci. USA 77: 2500–2504.

    Article  CAS  Google Scholar 

  8. Liebman, P.A. and Pugh, E.N., Jr. 1979. The control of phosphodiesterase in rod disk membranes: kinetics, possible mechanisms and significance for vision. Vision Res. 19: 375–380.

    Article  CAS  Google Scholar 

  9. Farber, D.B., Brown, B.M. and Lolley, R.N. 1978. Cyclic GMP: proposed role in visual cell function. Vision Res. 18: 497–499.

    Article  CAS  Google Scholar 

  10. Woodruff, M.L. and Bownds, D. 1979. Amplitude, kinetics, and reversibility of a light-induced decrease in guanosine 3′,5′-cyclic monophosphate in frog photoreceptor membranes. J. Gen. Physiol. 73: 629–653.

    Article  CAS  Google Scholar 

  11. Woodruff, M.L., Bownds, D., Steven, H., Green, J.L. and Shed-lovsky, A. 1977. Guanosine 3′,5′-cyclic monophosphate and the in vitro physiology of frog photoreceptor membranes. J. Gen. Physiol. 69: 667–669.

    Article  CAS  Google Scholar 

  12. Kilbride, P. and Ebrey, T.G. 1979. Light-induced changes of cyclic guanosine monophosphate levels in the frog retina measured with quick-freezing. J. Gen. Physiol. 74: 415–426.

    Article  CAS  Google Scholar 

  13. Ames, A. III and Nesbett, F.B. 1981. In vitro retina as an experimental model of the central nervous system. J. Neurochem. 37: 867–877.

    Article  CAS  Google Scholar 

  14. Berger, S.J., Devries, G.W., Carter, J.G., Schulz, D.W., Passonneau, P.N., Lowry, O.H. and Ferrendelli, J.A. 1980. The distribution of the components of the cyclic GMP cycle in retina. J. Biol. Chem. 255: 3128–3133.

    CAS  PubMed  Google Scholar 

  15. Goldberg, N.D., Ames, A. III, Gander, J.E. and Walseth, T.F. 1983. Magnitude of increase in retinal cGMP metabolic flux determined by 18O incorporation into nucleotide alpha-phosphoryls corresponds with intensity of photic stimulation. J. Biol. Chem. 258: 9213–9219.

    CAS  PubMed  Google Scholar 

  16. Heyman, R., Ames, A. III, Walseth, T., Barad,M., Graeff, R. and Goldberg,N. 1985. Biophysical Society Abstracts, in press.

    Google Scholar 

  17. Hagins, W.A. 1972. The visual process: excitatory mechanisms in the primary receptor cell. Annu. Rev. Biophys. Bioeng. 1: 131–138.

    Article  CAS  Google Scholar 

  18. Koshland, D.E., Jr., 1981. Biochemistry of sensing and adaptation in a simple bacterial system. Annu. Rev. Biochem. 50: 765–782.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goldberg, N., Walseth, T. A Second Role for Second Messengers: Uncovering the Utility of Cyclic Nucleotide Hydrolysis. Nat Biotechnol 3, 235–238 (1985). https://doi.org/10.1038/nbt0385-235

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0385-235

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing