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Cyclic GMP-Hydrolyzing Phosphodiesterases

  • Chapter
cGMP: Generators, Effectors and Therapeutic Implications

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 191))

Abstract

The cyclic nucleotides (cN), cAMP and cGMP, are key second messengers that mediate the intracellular effects of many signals known as “first messengers”, including environmental signals such as photons for vision and chemicals for taste, as well as hormones, paracrine factors, neurotransmitters, or autocrine factors. Many “first messengers” affect the level of cAMP and/or cGMP thereby initiating increased or decreased signaling selectively through cAMP- or cGMP-signaling pathways. cAMP and cGMP are synthesized by adenylyl cyclases and guanylyl cyclases, respectively, and degraded by a large superfamily of cN phosphodiesterases (PDE). Following the discovery of cAMP (Rall and Sutherland 1958), the search for the role of cAMP in modulating a wide variety of biological processes quickly ensued. Cyclic GMP was discovered in 1963, but many years elapsed before cGMP signaling proved to be a powerful and selective physiological process in its own right. Sutherland and colleagues reasoned that for cNs to be biologically relevant, there must be a mechanism for their removal from the cellular milieu. In 1958 they reported that heart extracts contained PDE activity that dampened or terminated the action of cAMP, and this PDE activity was blocked by methylxanthines, i.e., caffeine and theophylline (Butcher and Sutherland 1962). This was the first report of PDE action and identification of PDE inhibitors.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Light Hall Room 702, Nashville, TN, 37232-0615, USA

    Sharron H. Francis & Jackie D. Corbin

  2. Bayer Schering Pharma AG, Cardiology Research, Pharma Research Center, Wuppertal, 42096, Germany

    Erwin Bischoff

Authors
  1. Sharron H. Francis
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  2. Jackie D. Corbin
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  3. Erwin Bischoff
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Corresponding author

Correspondence to Sharron H. Francis .

Editor information

Editors and Affiliations

  1. Dept. Pharmacology, Monash University, Wellington Road, Clayton, VIC, 3800, Australia

    Harald H. H. W. Schmidt

  2. Inst. Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, München, 80802, Germany

    Franz Hofmann

  3. Bayer Schering Pharma AG Cardiology Research, Pharma Research Center, Wuppertal, 42096, Germany

    Johannes-Peter Stasch

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Francis, S.H., Corbin, J.D., Bischoff, E. (2009). Cyclic GMP-Hydrolyzing Phosphodiesterases. In: Schmidt, H.H.H.W., Hofmann, F., Stasch, JP. (eds) cGMP: Generators, Effectors and Therapeutic Implications. Handbook of Experimental Pharmacology, vol 191. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68964-5_16

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