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The role of phosphodiesterases in bladder pathophysiology

Nature Reviews Urology volume 10, pages 414–424 (2013)Cite this article

Subjects

Abstract

Nitric oxide and the cyclic nucleotide monophosphates cAMP and cGMP have a role in control of the micturition process and hence, are suggested to be involved in the pathophysiology of storage and voiding disorders. Phosphodiesterase enzymes (PDEs) hydrolyse cAMP and cGMP. Inhibition of PDEs increases cAMP and cGMP levels and relaxes urinary bladder smooth musculature. Although many preclinical studies have been conducted, to date, only PDE1 and PDE5 inhibitors have been tested clinically for the management of storage and voiding disorders. Treatment with PDE1 inhibitors might improve micturition frequency in patients with overactive bladder, whereas inhibition of PDE5 improves lower urinary tract symptoms in men, either with or without BPH and erectile dysfunction (ED). Furthermore, the combination of a PDE5 inhibitor and an α-adrenoceptor antagonist has superior efficacy to monotherapy with either agent. However, the role of PDE5 inhibitors in the treatment of women with detrusor overactivity remains unclear. The clinical application of agents that inhibit other PDEs, including PDE4, also certainly merits scientific attention. PDE inhibitors seem likely to become a valuable alternative treatment for patients with storage and voiding disorders in the future.

Key Points

  • Phosphodiesterases (PDEs) hydrolyse cAMP and cGMP, and are thought to have a crucial role in bladder physiology

  • Inhibition of PDEs raises cAMP and cGMP levels and relaxes urinary bladder muscles

  • Although PDEs 1–5 and 7–9 occur in the human urinary bladder, only PDE1 and PDE5 inhibitors have been clinically tested for the treatment of storage and voiding disorders

  • PDE1 inhibition improves micturition frequency

  • PDE5 inhibition alleviates lower urinary tract symptoms in men, including those with and without BPH and erectile dysfunction

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Figure 1: Schematic diagram of the cyclic nucleotide signalling pathways.
Figure 2: A schematic overview of the different PDE isoenzymes and some of their characteristics, including affinity for cAMP and cGMP.
Figure 3: Phosphodiesterases and innervation in the male lower urinary tract.

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Authors and Affiliations

  1. Department of Urology, Maastricht University Medical Centre, P. O. Box 5800, Maastricht, 6202 AZ, The Netherlands

    Mohammad S. Rahnama'i & Gommert A. van Koeveringe

  2. Department of Urology & Urological Oncology, Division of Surgery, Feodour-Lynen-Strasse 35, Medical Park Business Area, Hannover Medical School, Hannover, 30625, Germany

    Stefan Ückert

  3. The Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience, Maastricht University, P. O. Box 616, Maastricht, 6200 MD, The Netherlands

    Ramona Hohnen

Authors
  1. Mohammad S. Rahnama'i
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  2. Stefan Ückert
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  3. Ramona Hohnen
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  4. Gommert A. van Koeveringe
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Contributions

M. S. Rahnama'i wrote the article. In addition, M. S. Rahnamai and R. Hohnen researched the data for the article, and M. S. Rahnama'i, S. Ückert and G. A. van Koeveringe contributed substantially to discussions of the content and review or editing of the manuscript before submission.

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Correspondence to Mohammad S. Rahnama'i.

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The authors declare no competing financial interests.

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Rahnama'i, M., Ückert, S., Hohnen, R. et al. The role of phosphodiesterases in bladder pathophysiology. Nat Rev Urol 10, 414–424 (2013). https://doi.org/10.1038/nrurol.2013.101

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