Skip to main content
SpringerLink
Log in

Cyclic Nucleotide Phosphodiesterases

  • Chapter
Cell Regulation by Intracellular Signals

Part of the book series: NATO Advanced Study Institutes Series ((NSSA,volume 44))

  • 38 Accesses

Abstract

Once adenosine 3′,5′-monophosphate (cyclic AMP) was established as the heat stable factor that mediated the activation of liver phosphorylase by epinephrine and glucagonl, the search began to identify an enzyme to inactivate the factor. A number of general phosphatases and diesterases failed to affect it. However, an enzyme capable of destroying the biological activity of cyclic AMP was detected in extracts of heart, brain and liver2. The enzyme was later identified in a great many tissues3 and shown to form adenosine 5′-phosphate as the product of hydrolysis. Partially purified enzyme activity from dog heart was activated by magnesium ion and inhibited by the methylxanthine caffeine. The possible complexity of this activity, as a system, was indicated by its presence in soluble as well as particulate fractions. Approximately 60% of the phosphodiesterase activity in homogenates of beef heart was found to be associated with particulate fractions after low-speed centrifugation. The apparent Km of the partially purified soluble enzyme activity was around 100pM. It was inhibited, in a competitive manner, by theophylline>theobromine = caffeine. The activity was stimulated by imidazole which shifted the pH optima for enzyme activity from around 8 (in tris buffer) to approximately 7.4. Subsequent attempts to purify phosphodiesterase from other tissue sources, e.g., rabbit brain4, dog heart5 and rat brain6 failed to yield enzyme preparations with specific activities greater than those reported for the beef heart enzyme3.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. T. W. Rall and E. W. Sutherland, J. Biol. Chem. 232: 105 (1958).

    Google Scholar 

  2. E. W. Sutherland and T. W. Rall, J. Biol. Chem. 232: 1077 (1958).

    PubMed  CAS  Google Scholar 

  3. R. W. Butcher and E. W. Sutherland, J. Biol. Chem. 237: 1244 (1962).

    PubMed  CAS  Google Scholar 

  4. G. I. Drummond and S. Perrott-Yee, J. Biol Chem. 236: 1126 (1962).

    Google Scholar 

  5. K. G. Nair, Biochemistery 5: 150 (1966).

    Article  CAS  Google Scholar 

  6. W. Y. Cheung, Biochemistery 6: 1079 (1966).

    Article  Google Scholar 

  7. G. Brooker, L. J. Thomas and M. M. Appleman, Biochemistry 7: 4177 (1968).

    Article  PubMed  CAS  Google Scholar 

  8. W. J. Thompson and M. M. Appleman, Biochemistry 7: 4177 (1968).

    Article  Google Scholar 

  9. T. R. Russell, W. J. Thompson, F. W. Schneider and M. M. Appleman, Proc. Natl. Acad. Sci. U.S.A. 69: 1791 (1972).

    Article  CAS  Google Scholar 

  10. W. J. Appleman and M. M. Appleman, J. Biol. Chem. 246: 3145 (1971).

    PubMed  CAS  Google Scholar 

  11. J. N. Wells and J. G. Hardman, Adv. Cyclic Nucl. Res. 8: 119 (1977).

    CAS  Google Scholar 

  12. S. J. Strada and W. J. Thompson, Adv. Cyclic Nucl. Res. 9: 265 (1978).

    CAS  Google Scholar 

  13. W. J. Thompson, P. M. Epstein and S. J. Strada, Biochemistry 18: 5228 (1979).

    Article  PubMed  CAS  Google Scholar 

  14. R. K. Sharma, T. H. Wang, E. Wirch and J. H. Wang, J. Biol. Chem. 255: 5916 (1980).

    PubMed  CAS  Google Scholar 

  15. W. J. Thompson, G. Brooker and M. M. Appleman, Methods Enzymol 38: 205 (1974).

    Article  PubMed  CAS  Google Scholar 

  16. W. J. Thompson and M. M. Appleman, Biochemistry 10: 311 (1979).

    Google Scholar 

  17. W. J. Thompson, W. J. Terasaki, P. M. Epstein and S. J. Strada, Adv. Cyclic Nucl. Res. 10: 69 (1979).

    CAS  Google Scholar 

  18. J. Londesborough, Anal. Biochem. 71: 623 (1976).

    Article  PubMed  CAS  Google Scholar 

  19. T. R. Russell, W. L. Terasaki and M. M. Appleman, J. Biol. Chem. 248: 1334 (1973).

    PubMed  CAS  Google Scholar 

  20. W. L. Terasaki and M. M. Appleman, Metabolism 24: 311 (1975).

    Article  PubMed  CAS  Google Scholar 

  21. H. Hidaka and T. Asano, Biochim. Biophys. Acta 429: 485 (1976).

    Article  CAS  Google Scholar 

  22. R. G. Van Inwegen, W. J. Pledger S. J. Strada and W. J. Thompson, Arch. Biochem. Biophys. 175: 700 (1976).

    Article  PubMed  Google Scholar 

  23. P. Uzunov and B. Weiss, Biochim. Biophys. Acta 284: 220 (1972).

    Article  CAS  Google Scholar 

  24. S. J. Strada, P. Uzunov and B. Weiss, J. Neurochem. 23: 1097 (1974).

    Article  PubMed  CAS  Google Scholar 

  25. B. Weiss, R. Fertel, R. Figlin and P. Uzunov, Mol. Pharmacol. 10: 615 (1974).

    CAS  Google Scholar 

  26. B. Weiss, Adv. Cyclic Nucl. Res. 5: 195 (1975).

    CAS  Google Scholar 

  27. W. J. Thompson and S. J. Strada, in: “Receptors and Hormone Action”, Vol.3, L. Birnbaumer and B. W. O’Malley, 553 Academic Press, New York (1978).

    Google Scholar 

  28. R. J. Marchmont and M. D. Houslay, Nature 286: 904 (1980).

    Article  PubMed  CAS  Google Scholar 

  29. T. Kono, F. W. Robinson and J. A. Sarber, J. Biol. Chem. 250: 7826 (1975).

    PubMed  CAS  Google Scholar 

  30. A. Robertson and J. Grutsch, Life Sci. 15: 1031 (1976).

    Article  Google Scholar 

  31. S. J. Strada and W. J. Pledger, in: “Cyclic Nucleotides in Disease”, B. Weiss, ed., 3, University Park Press, Baltimore, Md. (1975).

    Google Scholar 

  32. W. J. Pledger, W. J. Thompson, P. M. Epstein and S. J. Strada, J. Cell. Physol. 100: 497 (1979).

    Article  CAS  Google Scholar 

  33. P. M. Epstein, J. S. Mills, E. M. Hersh, S. J. Strada and W. J. Thompson, Cancer Res. 40: 379 (1980).

    PubMed  CAS  Google Scholar 

  34. G. M. Stancel, W. J. Thompson and S. J. Strada, Molec. Cell. Endo. 3:283 (1975).

    Google Scholar 

  35. J. J. Heindel, M. I. Hintz, E. Steinberger and S. J. Strada, Endo. Res. Commun. 4: 311 (1977).

    Article  CAS  Google Scholar 

  36. B. Weiss and S. J. Strada in: “Fetal Pharmacology”, L. Boureus, ed., 205, Raven Press, New York (1973).

    Google Scholar 

  37. J. A. Smoake, S. Y. Song and W. Y. Cheung, Biochim. Biophys. Acta 341: 402 (1974).

    Article  CAS  Google Scholar 

  38. E. A. Gardner, W. J. Thompson, S. J. Strada and G. M. Stancel, Biochemistry 17: 2995 (1978).

    Article  PubMed  CAS  Google Scholar 

  39. E. G. Beale, J. R. Dedman and A. R. Means, Endocrinology 100: 1621 (1977).

    Article  Google Scholar 

  40. M. Vaughan, in:“Eukaryotic Cell Function and Growth: Regulation by Intracellular Cyclic Nucleotides”, J. E. Dumont,B. L. Brown and N. J. Marshall, 195, Plenum Press, New York (1976).

    Google Scholar 

  41. J. A. Nesbitt, W. B..Anderson, Z. Miller, I. Pastan, T. R. Russell and D. Gospodarowicz, J. Biol. Chem. 251: 2344 (1976).

    PubMed  CAS  Google Scholar 

  42. H. R. Bourne, G. M. Tomkins and S. Dion, Science 181: 952 (1973).

    Article  PubMed  CAS  Google Scholar 

  43. H. R. Bourne, P. Coffino, K. L. Thomkins, and Y. Weinstein, Adv. Cyclic Nucl. Res. 5: 771 (1975).

    CAS  Google Scholar 

  44. F. J. Chlapowski, L. A. Kelly and R. W. Butcher, Adv. Cyclic Nucl. Res. 5: 245 (1975).

    Google Scholar 

  45. W. J. Pledger, R. M. Gardner, P. M. Epstein, W. J. Thompson, S. J. Strada, and L. Wlodyka, Exptl. Cell Res. 118: 389 (1979).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, The University of Texas Medical School at Houston, Houston, Texas, 77030, USA

    Samuel J. Strada

Authors
  1. Samuel J. Strada
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Brussels Medical School, Brussels, Belgium

    Stéphane Swillens  & Jacques E. Dumont  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1982 Springer Science+Business Media New York

About this chapter

Cite this chapter

Strada, S.J. (1982). Cyclic Nucleotide Phosphodiesterases. In: Swillens, S., Dumont, J.E. (eds) Cell Regulation by Intracellular Signals. NATO Advanced Study Institutes Series, vol 44. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7718-4_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-7718-4_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-7720-7

  • Online ISBN: 978-1-4684-7718-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation