Sildenafil effect on the human bladder involves the L-cysteine/hydrogen sulfide pathway: A novel mechanism of action of phosphodiesterase type 5 inhibitors

European Urology

Volumn 62, Issue 6, 2012, Pages 1174-1180

  Fusco, Ferdinando ^a   D'Emmanuele Di Villa Bianca, Roberta ^a   Mitidieri, Emma ^a   Cirino, Giuseppe ^a   Sorrentino, Raffaella ^a   Mirone, Vincenzo ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Human bladder; Hydrogen sulfide; L cysteine; Lower urinary tract symptoms; Phosphodiesterase inhibitors; Sildenafil

Indexed keywords

8 BROMO CYCLIC GMP; BUCLADESINE; CYSTEINE; HYDROGEN SULFIDE; SILDENAFIL;

ADULT; AGED; ARTICLE; COLORIMETRY; DETRUSOR MUSCLE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; MALE; PRIORITY JOURNAL; PROSTATE HYPERTROPHY; PROSTATECTOMY; SMOOTH MUSCLE RELAXATION; WESTERN BLOTTING;

AGED; CYSTEINE; HUMANS; HYDROGEN SULFIDE; MALE; MIDDLE AGED; PHOSPHODIESTERASE 5 INHIBITORS; PIPERAZINES; PURINES; SIGNAL TRANSDUCTION; SULFONES; URINARY BLADDER;

EID: 84868558970     PISSN: 03022838     EISSN: 18737560     Source Type: Journal    
DOI: 10.1016/j.eururo.2012.07.025     Document Type: Article

References (30)

1. R. Rosen, J. Altwein, and P. Boyle Lower urinary tract symptoms and male sexual dysfunction: the Multinational Survey of the Aging Male (MSAM-7) Eur Urol 44 2003 637 649
2. C.R. Chapple, and C.G. Roehrborn A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder Eur Urol 49 2006 651 659
3. Oelke M, Bachmann A, Descazeaud A, et al., European Association of Urology Guidelines Office. Guidelines on the management of male lower urinary tract symptoms (LUTS), including benign prostatic obstruction (BPO). Presented at: 27th European Association of Urology annual congress; February 24-28, 2012; Paris, France.
4. S. Ückert, and M. Oelke Phosphodiesterase (PDE) inhibitors in the treatment of lower urinary tract dysfunction Br J Clin Pharmacol 72 2011 197 204
5. M. Conti, and S.L. Jin The molecular biology of cyclic nucleotide phosphodiesterases Prog Nucleic Acid Res Mol Biol 63 1999 1 38
6. S. Ückert, A. Küthe, U. Jonas, and C.G. Stief Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate J Urol 166 2001 2484 2490
7. M.C. Truss, S. Ückert, C.G. Stief, M.A. Kuczyk, and U. Jonas Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle: I. Identification and characterization Urol Res 24 1996 123 128
8. K.E. Andersson, W.C. de Groat, and K.T. McVary Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action Neurourol Urodyn 30 2011 292 301
9. J.A.F. Bittencourt Relaxant effects of sildenafil on the human isolated bladder neck Urology 73 2009 427 430
10. V. Werkström, A. Svensson, K.E. Andersson, and P. Hedlund Phosphodiesterase 5 in the female pig and human urethra: morphological and functional aspects BJU Int 98 2006 414 423
11. S. Oger, D. Behr-Roussel, and D. Gorny Signalling pathways involved in sildenafil-induced relaxation of human bladder dome smooth muscle Br J Pharmacol 160 2010 1135 1143
12. R. Dmochowski, C. Roehrborn, S. Klise, L. Xu, J. Kaminetsky, and S. Kraus Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial J Urol 183 2010 1092 1097
13. M. Gacci, G. Del Popolo, and A. Macchiarella Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study J Urol 178 2007 2040 2044
14. 2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder Br J Pharmacol 142 2004 31 34
15. R. d'Emmanuele di Villa Bianca, R. Sorrentino, and P. Maffia Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation Proc Natl Acad Sci U S A 106 2009 4513 4518
16. H. Guo, J.W. Gai, Y. Wang, H.F. Jin, J.B. Du, and J. Jin Characterization of hydrogen sulfide and its synthases, cystathionine β-synthase and cystathionine γ-lyase, in human prostatic tissue and cells Urology 79 2012 483.e1-5
17. R. Wang Physiological implications of hydrogen sulfide: a whiff exploration that blossomed Physiol Rev 92 2012 791 896
18. M. Bucci, A. Papapetropoulos, and V. Vellecco Hydrogen sulfide is an endogenous inhibitor of phosphodiesterase activity Arterioscler Thromb Vasc Biol 30 2010 1998 2004
19. M.H. Stipanuk, and P.W. Beck Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat Biochem J 206 1982 267 277
20. F.R. Báu, F.Z. Mónica, F.B. Priviero, L. Baldissera Jr., G. de Nucci, and E. Antunes Evaluation of the relaxant effect of the nitric oxide-independent soluble guanylyl cyclase stimulator BAY 41-2272 in isolated detrusor smooth muscle Eur J Pharmacol 637 2010 171 177
21. F.N. Salloum, V.Q. Chau, and N.N. Hoke Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide Circulation 120 2009 S31 S36
22. R. Patacchini, P. Santicioli, S. Giuliani, and C.A. Maggi Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle Eur J Pharmacol 509 2005 171 177
23. R.A. Dombkowski, M.M. Doellman, S.K. Head, and K.R. Olson Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle J Exp Biol 209 2006 3234 3240
24. M.C. Truss, S. Ückert, C.G. Stief, M.A. Kuczyk, and U. Jonas 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 1996 129 134
25. S. Oger, D. Behr-Roussel, and D. Gorny Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition Eur Urol 51 2007 772 781
26. E. Bischoff Potency, selectivity, and consequences of nonselectivity of PDE inhibition Int J Impot Res 16 2004 S11 S14
27. C. Zhao, S.H. Kim, and S.W. Lee Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia BJU Int 107 2011 1943 1947
28. V. Werkström, P. Hedlund, T. Lee, and K.E. Andersson Vardenafil-induced relaxation and cyclic nucleotide levels in normal and obstructed rat urinary bladder BJU Int 104 2009 1740 1745
29. C. Peers, C.C. Bauer, J.P. Boyle, J.L. Scragg, and M.L. Dallas Modulation of ion channels by hydrogen sulfide Antioxid Redox Signal 17 2012 95 105
30. C. Gratzke, P. Weinhold, and O. Reich Transient receptor potential A1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells Eur Urol 57 2010 902 910