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.

  • Original Research
  • Published:

3′,5′-Cyclic nucleotide phosphodiesterase 11A: localization in human tissues

Abstract

3′,5′-Cyclic nucleotide phosphodiesterase 11 (PDE11) is the most recently discovered family of human 3′,5′-cyclic nucleotide phosphodiesterases (PDEs). This family contains one gene, PDE11A, with four splice variants (PDE11A1–PDE11A4). The physiological role of PDE11A has not been determined. Tadalafil (Cialis®), a PDE5A inhibitor used for the treatment of male erectile dysfunction, has been reported to partially inhibit PDE11. It was therefore of interest to consider the pattern of expression of PDE11 in human tissues. Although four PDE11A mRNA transcripts have been reported, we detected protein corresponding to only one of them, PDE11A4, in human prostate, pituitary, heart and liver. Using immunohistochemistry, there was strong PDE11A antibody staining in the glandular epithelium of the prostate and weak staining of neuronal cells within parasympathetic ganglia in the heart. No PDE11A protein was detected in blood vessels or cardiac myocytes. None of the four potential PDE11A proteins were detected in human skeletal muscle, testis, or penis.

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Francis SH, Turko IV, Corbin JD . Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol 2001; 65: 1–52.

    CAS  Google Scholar 

  2. Fawcett L et al. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Nat Acad Sci USA 2000; 97: 3702–3707.

    Article  CAS  Google Scholar 

  3. Hetman JM et al. Cloning and characterization of two splice variants of human phosphodiesterase 11A. Proc Nat Acad Sci USA 2000; 97: 12891–12895.

    Article  CAS  Google Scholar 

  4. Yuasa K et al. Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. J Biol Chem 2000; 275: 31469–31479.

    Article  CAS  Google Scholar 

  5. Saenz de Tejada I, Argulo Frutos J, Gadau M, Florio V . Comparative selectivity profiles of tadalafil, sildenafil and vardenafil using an in vitro phosphodiesterase activity assay. Int J Impot Res 2002; 14(Suppl 4): S20.

    Google Scholar 

  6. Gbekor E et al. Phosphodiesterase 5 inhibitor profiles against all human phosphodiesterase families: implications for use as pharmacological tools. J Urol 2002; 167(Suppl): 246.

    Google Scholar 

  7. Yuasa K, Kanoh Y, Okumura K, Omori K . Genomic organization of the human phosphodiesterase PDE11A gene: evolutionary relatedness with other PDEs containing GAF domains. Eur J Biochem 2001; 268: 168–178.

    Article  CAS  Google Scholar 

  8. Baxendale RW, Burslem F, Phillips SC . Phosphodiesterase type 11 (PDE11) cellular localisation: progress towards defining a physiological role in testis and/or reproduction. J Urol 2001; 165(Suppl): 340.

    Google Scholar 

  9. Baxendale R, Phillips SC . Human PDE11: a distinct, dual-substrate phosphodiesterase expressed in vascular smooth muscle and cardiac myocytes. Circulation 2000; 102(Suppl): II320.

    Google Scholar 

  10. Baxendale RW, Wayman CP, Turner L, Phillips SC . Cellular localisation of phosphodiesterase type 11 (PDE11) in human corpus cavernosum and the contribution of PDE11 inhibition on nerve-stimulated relaxation. J Urol 2001; 165(Suppl): 233–234.

    Google Scholar 

  11. Ueckert S et al. Immunohistochemical presence of phosphodiesterase (PDE)11A in the human prostate. J Urol 2004; 171(Suppl): 352.

    Article  Google Scholar 

  12. Ueckert S et al. Immunohistochemical presence of phosphodiesterase (PDE)11A in the human prostate. Eur Urol 2004; 3(Suppl): 18.

    Article  Google Scholar 

  13. Sadhu K, Hensley K, Florio VA, Wolda SL . Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. J Histochem Cytochem 1999; 47: 895–905.

    Article  CAS  Google Scholar 

  14. Running Deer J, Allison DS . High-level expression of proteins in mammalian cells using transcription regulatory sequences from the Chinese hamster EF-1 alpha gene. Biotechnol Prog 2004; 20: 880–889.

    Article  Google Scholar 

  15. Harlow E, Lane D . Antibodies: a laboratory manual. Cold Spring Harbor Laboratory Press: NY, 1990.

    Google Scholar 

  16. Yuasa K, Ohgaru T, Asahina M, Omori K . Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A): comparison of rat and human PDE11A splicing variants. Eur J Biochem 2001; 268: 4440–4448.

    Article  CAS  Google Scholar 

  17. Goldberg E et al. Cytochrome c: immunofluorescent localization of the testis-specific form. Science 1977; 196: 1010–1012.

    Article  CAS  Google Scholar 

  18. Zhang Z, Gerstein M . The human genome has 49 cytochrome c pseudogenes including a relic of a primordial gene that still functions in mouse. Gene 2003; 312: 61–72.

    Article  CAS  Google Scholar 

  19. James LC, Roversi P, Tawfik DS . Antibody multispecificity mediated by conformational diversity. Science 2003; 299: 1362–1367.

    Article  CAS  Google Scholar 

  20. Weeks JLII et al. High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests absence of PDE11A4 cross-reaction in patients. Int J Impot Res 2005; 17: 5–9.

    Article  CAS  Google Scholar 

  21. Jackson G et al. Update on clinical trials of tadalafil demonstrates no increased risk of cardiovascular adverse events. J Sex Med 2004; 1: 161–167.

    Article  CAS  Google Scholar 

  22. Carson CC et al. The efficacy and safety of tadalafil: an update. BJU Int 2004; 93: 1276–1281.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Mike Gadau, Lothar Uher, Peter Snyder, Guy Rosman, Sharon Wolda, Esther Trueblood, Kim Nordstrom McCaw and Krishna Sadhu for their contributions. This work was sponsored by Lilly Icos LLC and by Icos Corporation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K Loughney.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loughney, K., Taylor, J. & Florio, V. 3′,5′-Cyclic nucleotide phosphodiesterase 11A: localization in human tissues. Int J Impot Res 17, 320–325 (2005). https://doi.org/10.1038/sj.ijir.3901317

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3901317

Keywords

This article is cited by

Search

Quick links