Skip to main content

Advertisement

SpringerLink
Log in

Phosphodiesterase type 2 distribution in the guinea pig urinary bladder

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Introduction

Nitric oxide-stimulated cGMP synthesis represents an important signalling pathway in the urinary bladder. Inhibitors of the PDE1 and PDE5 enzyme have been studied to treat storage and voiding disorders in clinical settings. The distribution of PDE2 in the bladder is unknown. This study focuses on the distribution and site of action of PDE2 within the guinea pig urinary bladder wall.

Methods

Six male guinea pig bladders were dissected and treated in 2 ml Krebs’ solution and 10 µM of the specific PDE2 inhibitor, Bay 60-7550 at 36 °C for 30 min. After stimulating tissues with 100 µM of diethylamine-NONOate for 10 min, the tissues were snap frozen and cut in 10 µm sections which were examined for cGMP immune-reactivity, co-stained with either vimentin, synaptic vesicle protein 2, calcitonin gene-related protein and protein gene product 9.5.

Results

PDE2 inhibitor Bay 60-7550 inhibits cGMP breakdown the most in the urothelial and suburothelial layers, as well as on the nerve fibres. After inhibition by Bay 60-7550, cGMP was mainly expressed in the intermuscle interstitial cells and the nerve fibres of the outer muscle layers of lateral wall, indicating the presence of PDE2 activity.

Discussion and conclusion

Our study is the first to show the distribution of PDE2 in the bladder which was shown to be present in the urothelium, mainly umbrella cells, the interstitial cells of the suburothelium and the outer muscle, as well as in nerve fibres.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Smet PJ, Jonavicius J, Marshall VR, de Vente J (1996) Distribution of nitric oxide synthase-immunoreactive nerves and identification of the cellular targets of nitric oxide in guinea-pig and human urinary bladder by cGMP immunohistochemistry. Neuroscience 71(2):337–348

    Article  CAS  PubMed  Google Scholar 

  2. Gillespie JI, Drake MJ (2004) The actions of sodium nitroprusside and the phosphodiesterase inhibitor dipyridamole on phasic activity in the isolated guinea-pig bladder. BJU Int 93(6):851–858

    Article  CAS  PubMed  Google Scholar 

  3. de Jongh R, van Koeveringe GA, van Kerrebroeck PE, Markerink-van Ittersum M, de Vente J, Gillespie JI (2007) Alterations to network of NO/cGMP-responsive interstitial cells induced by outlet obstruction in guinea-pig bladder. Cell Tissue Res 330(1):147–160

    Article  PubMed  Google Scholar 

  4. Gillespie JI, Markerink-van Ittersum M, De Vente J (2006) Endogenous nitric oxide/cGMP signalling in the guinea pig bladder: evidence for distinct populations of sub-urothelial interstitial cells. Cell Tissue Res 325(2):325–332

    Article  CAS  PubMed  Google Scholar 

  5. Gillespie JI, Markerink-van Ittersum M, de Vente J (2005) Expression of neuronal nitric oxide synthase (nNOS) and nitric-oxide-induced changes in cGMP in the urothelial layer of the guinea pig bladder. Cell Tissue Res 321(3):341–351

    Article  CAS  PubMed  Google Scholar 

  6. Gillespie JI, Markerink-van Ittersum M, de Vente J (2004) cGMP-generating cells in the bladder wall: identification of distinct networks of interstitial cells. BJU Int 94(7):1114–1124

    Article  PubMed  Google Scholar 

  7. Beavo JA (1995) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 75(4):725–748

    CAS  PubMed  Google Scholar 

  8. de Vente J, Markerink-vanIttersum M, Vles JS (2006) The role of phosphodiesterase isoforms 2, 5, and 9 in the regulation of NO-dependent and NO-independent cGMP production in the rat cervical spinal cord. J Chem Neuroanat 31(4):275–303

    Article  PubMed  Google Scholar 

  9. Archer SL, Michelakis ED (2009) Phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension. N Engl J Med 361(19):1864–1871

    Article  CAS  PubMed  Google Scholar 

  10. Rosenzweig EB (2010) Tadalafil for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother 11(1):127–132. doi:10.1517/14656560903413542

    Article  CAS  PubMed  Google Scholar 

  11. Feldman AM, McNamara DM (2002) Reevaluating the role of phosphodiesterase inhibitors in the treatment of cardiovascular disease. Clin Cardiol 25(6):256–262

    Article  PubMed  Google Scholar 

  12. Halene TB, Siegel SJ (2007) PDE inhibitors in psychiatry: future options for dementia, depression and schizophrenia? Drug Discov Today 12(19–20):870–878

    Article  CAS  PubMed  Google Scholar 

  13. Morales AM, Mirone V, Dean J, Costa P (2009) Vardenafil for the treatment of erectile dysfunction: an overview of the clinical evidence. Clin Interv Aging 4:463–472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Rowlands TE, Donnelly R (2007) Medical therapy for intermittent claudication. Eur J Vasc Endovasc Surg 34(3):314–321

    Article  CAS  PubMed  Google Scholar 

  15. Rahnama’i MS, Uckert S, Hohnen R, van Koeveringe GA (2013) The role of phosphodiesterases in bladder pathophysiology. Nat Rev Urol 10(7):414–424

    Article  PubMed  Google Scholar 

  16. Uckert S, Kuczyk MA, Oelke M (2013) Phosphodiesterase inhibitors in clinical urology. Expert Rev Clin Pharmacol 6(3):323–332

    Article  PubMed  Google Scholar 

  17. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC et al (2013) EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 64(1):118–140

    Article  PubMed  Google Scholar 

  18. Fock EM, Lavrova EA, Bachteeva VT, Chernigovskaya EV, Parnova RG (2004) Nitric oxide inhibits arginine-vasotocin-induced increase of water osmotic permeability in frog urinary bladder. Pflug Arch 448(2):197–203

    Article  CAS  Google Scholar 

  19. Zhai K, Chang Y, Wei B, Liu Q, Leblais V, Fischmeister R et al (2014) Phosphodiesterase types 3 and 4 regulate the phasic contraction of neonatal rat bladder smooth myocytes via distinct mechanisms. Cell Signal 26(5):1001–1010

    Article  CAS  PubMed  Google Scholar 

  20. Truss MC, Uckert S, Stief CG, Forssmann WG, Jonas U (1996) Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. II. Effect of various PDE inhibitors on smooth muscle tone and cyclic nucleotide levels in vitro. Urol Res 24(3):129–134

    Article  CAS  PubMed  Google Scholar 

  21. Uckert S, Kuthe A, Jonas U, Stief CG (2001) Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol 166(6):2484–2490

    Article  CAS  PubMed  Google Scholar 

  22. Podzuweit T, Nennstiel P, Muller A (1995) Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine. Cell Signal 7(7):733–738

    Article  CAS  PubMed  Google Scholar 

  23. Boess FG, Hendrix M, van der Staay FJ, Erb C, Schreiber R, van Staveren W et al (2004) Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology 47(7):1081–1092

    Article  CAS  PubMed  Google Scholar 

  24. Rahnama’i MS, van Koeveringe GA, Hohnen R, Ona S, van Kerrebroeck PE, de Wachter SG (2013) Distribution of phosphodiesterase type 5 (PDE5) in the lateral wall of the guinea pig urinary bladder. BJU Int 112(2):246–257

    Article  PubMed  Google Scholar 

  25. de Vente J, Markerink-van Ittersum M, Axer H, Steinbusch HW (2001) Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain. Exp Brain Res 136(4):480–491

    Article  PubMed  Google Scholar 

  26. van Staveren WC, Steinbusch HW, Markerink-van Ittersum M, de Behrends S, Vente J (2004) Species differences in the localization of cGMP-producing and NO-responsive elements in the mouse and rat hippocampus using cGMP immunocytochemistry. Eur J Neurosci 19(8):2155–2168

    Article  PubMed  Google Scholar 

  27. Himms-Hagen J, Cui J, Lynn Sigurdson S (1990) Sympathetic and sensory nerves in control of growth of brown adipose tissue: effects of denervation and of capsaicin. Neurochem Int 17(2):271–279

    Article  CAS  PubMed  Google Scholar 

  28. Kong JH, Adelman JP, Fuchs PA (2008) Expression of the SK2 calcium-activated potassium channel is required for cholinergic function in mouse cochlear hair cells. J Physiol 586(Pt 22):5471–5485

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Kuniyoshi K, Ohtori S, Ochiai N, Murata R, Matsudo T, Yamada T et al (2007) Characteristics of sensory DRG neurons innervating the wrist joint in rats. Eur J Pain 11(3):323–328

    Article  PubMed  Google Scholar 

  30. Ramos-Vara JA, Miller MA (2007) Immunohistochemical detection of protein gene product 9.5 (PGP 9.5) in canine epitheliotropic T-cell lymphoma (mycosis fungoides). Vet Pathol 44(1):74–79

    Article  CAS  PubMed  Google Scholar 

  31. Sadhu K, Hensley K, Florio VA, Wolda SL (1999) Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. J Histochem Cytochem 47(7):895–906

    Article  CAS  PubMed  Google Scholar 

  32. Rahnama’i MS, van Koeveringe GA, Essers PB, de Wachter SG, de Vente J, van Kerrebroeck PE et al (2010) Prostaglandin receptor EP1 and EP2 site in guinea pig bladder urothelium and lamina propria. J Urol 183(3):1241–1247. doi:10.1016/j.juro.2009.11.004

    Article  PubMed  Google Scholar 

  33. Lagou M, Drake MJ, Markerink-Van Ittersum M, De Vente J, Gillespie JI (2006) Interstitial cells and phasic activity in the isolated mouse bladder. BJU Int 98(3):643–650

    Article  CAS  PubMed  Google Scholar 

  34. Park H, Clark E, Conklin JL (2003) Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions. Neurogastroenterol Motil 15(6):625–633

    Article  CAS  PubMed  Google Scholar 

  35. de Groat WC, Yoshimura N (2009) Afferent nerve regulation of bladder function in health and disease. Handb Exp Pharmacol 194:91–138

    Article  PubMed  Google Scholar 

  36. Birder LA (2006) Urinary bladder urothelium: molecular sensors of chemical/thermal/mechanical stimuli. Vasc Pharmacol 45(4):221–226

    Article  CAS  Google Scholar 

  37. Smet PJ, Moore KH, Jonavicius J (1997) Distribution and colocalization of calcitonin gene-related peptide, tachykinins, and vasoactive intestinal peptide in normal and idiopathic unstable human urinary bladder. Lab Invest 77(1):37–49

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Maastricht University Medical Centre (MUMC+), PO Box 5800, 6202 AZ, Maastricht, The Netherlands

    M. S. Rahnama’i, Ph. E. V. Van Kerrebroeck & G. A. van Koeveringe

  2. The Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands

    M. S. Rahnama’i, R. Hohnen, Ph. E. V. Van Kerrebroeck & G. A. van Koeveringe

Authors
  1. M. S. Rahnama’i
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Hohnen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ph. E. V. Van Kerrebroeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. A. van Koeveringe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. S. Rahnama’i.

Additional information

Dr. M.S. Rahnama’i and R. Hohnen have contributed almost equally to this paper and can be considered as joint first author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rahnama’i, M.S., Hohnen, R., Van Kerrebroeck, P.E.V. et al. Phosphodiesterase type 2 distribution in the guinea pig urinary bladder. World J Urol 33, 1623–1633 (2015). https://doi.org/10.1007/s00345-014-1455-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-014-1455-6

Keywords

Search

Navigation