Distribution of phosphodiesterase type 5 (PDE5) in the lateral wall of the guinea pig urinary bladder

Authors

  • Mohammad S. Rahnama'i,

    Corresponding author
    1. European Graduate School of Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
    • Department of Urology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
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  • Gommert A. van Koeveringe,

    1. Department of Urology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
    2. European Graduate School of Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
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  • Ramona Hohnen,

    1. European Graduate School of Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
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  • Samsya Ona,

    1. Lehman College of The City University of New York, New York, NY, USA
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  • Philip E.V. van Kerrebroeck,

    1. Department of Urology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
    2. European Graduate School of Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
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  • Stefan G.G. de Wachter

    1. Department of Urology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands
    2. European Graduate School of Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
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Correspondence: Mohammad S. Rahnama'i, Department of Urology, Maastricht University Medical Centre, P. Debeyelaan 25, Maastricht, PO Box 5800, 6202 AZ, The Netherlands.

e-mail: sajjad_r@yahoo.com

Abstract

Objective

  • To study PDE5 localisation by visualising the product of phosphodiesterase type 5 (PDE5) inhibition, namely cGMP, to determine the site of action of inhibitors in the urinary bladder.

Materials and Methods

  • Bladders of nine male guinea pigs were dissected and treated in wells containing 2 mL Krebs' solution and 1 μM of the specific PDE5 inhibitor vardenafil at 36 °C for 30 min.
  • After stimulating tissues with 100 μM of the nitric oxide (NO) donor diethylamine-NONOate for 10 min, the tissues were snap-frozen and 9–10 μm sections were cut.
  • Sections were examined for cGMP immunoreactivity and also stained for vimentin, a marker for interstitial cells and the neuromarkers protein gene product 9.5 (PGP9.5), synaptic vesicle protein 2 (SV2), neurofilament (NF) and calcitonin gene-related peptide (CGRP), using the two-step indirect immunohistochemistry technique.

Results

  • After PDE5 inhibition, cGMP was found to be present in the urothelium, suburothelial interstitial cells and endothelium of blood vessels.
  • cGMP was not expressed in nerves positive for CGRP, NF and SV2, and was expressed only in very few efferent nerves positive for PGP9.5.

Conclusion

  • Our data show that the possible sites of action of PDE5 inhibition in the bladder are the urothelium, suburothelial interstitial cells and blood vessels, rather than the bladder nerve fibres.

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