Update on Phosphodiesterase (PDE) Isoenzymes as Pharmacologic Targets in Urology: Present and Future{A figure is presented}

European Urology

Volumn 50, Issue 6, 2006, Pages 1194-1207

  Ückert, Stefan ^a,d   Hedlund, Petter ^b   Andersson, Karl Erik ^b   Truss, Michael C ^a   Jonas, Udo ^a   Stief, Christian G ^c  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^d IPF PHARMACEUTICALS GMBH   (Germany)

Author keywords

Human urogenital tract; Phosphodiesterase (PDE) enzymes; Phosphodiesterase inhibitors

Indexed keywords

1 [6 CHLORO 4 (3,4 METHYLENEDIOXYBENZYLAMINO) 2 QUINAZOLINYL] 4 PIPERIDINECARBOXYLIC ACID; 3 ISOBUTYL 8 METHOXYMETHYL 1 METHYLXANTHINE; 4 (3 BUTOXY 4 METHOXYBENZYL) 2 IMIDAZOLIDINONE; AMRINONE; CILOSTAMIDE; CP 461; ENOXIMONE; ETAZOLATE; GLYCERYL TRINITRATE; ISOENZYME; LINSIDOMINE; MILRINONE; N [[3 (4,7 DIHYDRO 1 METHYL 7 OXO 3 PROPYL 1H PYRAZOLO[4,3 D]PYRIMIDIN 5 YL) 4 PROPOXYPHENYL]SULFONYL] 1 METHYL 2 PYRROLIDINEPROPANAMIDE; NITRIC OXIDE DONOR; NITROPRUSSIDE SODIUM; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE V INHIBITOR; PROSTAGLANDIN E1; QUAZINONE; ROFLUMILAST; SIGUAZODAN; SILDENAFIL; SILDENAFIL NITRATE; TA 1709; TA 1790; TADALAFIL; TREQUINSIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VARDENAFIL; VASOACTIVE INTESTINAL POLYPEPTIDE; VINPOCETINE; ZAPRINAST; ZARDAVERINE; ZK 803616;

BACKACHE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG INDUCED HEADACHE; DYSPEPSIA; ENZYME INHIBITION; ERECTILE DYSFUNCTION; FEMALE SEXUAL DYSFUNCTION; FLUSHING; GENE TARGETING; HUMAN; HYPOTENSION; MORBIDITY; NOSE CONGESTION; OVERACTIVE BLADDER; PREMATURE EJACULATION; PREVALENCE; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATISM; REVIEW; SIDE EFFECT; URINARY TRACT DISEASE; UROGENITAL SYSTEM; UROLITHIASIS; VISUAL DISORDER;

FEMALE; FEMALE UROGENITAL DISEASES; HUMANS; MALE; MALE UROGENITAL DISEASES; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; TREATMENT OUTCOME; UROLOGY;

EID: 33750633515     PISSN: 03022838     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.eururo.2006.05.025     Document Type: Review

References (119)

1. Antoni F.A. Molecular diversity of cAMP signaling. Front Neuroendocrinol 21 (2000) 103-112
2. Lucas K.A., Pitari G.M., Kazerounian S., et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 52 (2000) 375-414
3. Andersson K.E. Pharmacology of lower urinary tract smooth muscle and penile erectile tissues. Pharmacol Rev 45 (1993) 253-308
4. Vemulapalli S., and Kurowski S. Sildenafil relaxes rabbit clitoral corpus cavernosum. Life Sci 67 (2000) 23-29
5. Kim S.W., Jeong S.J., Kim N.N., and Traish A.M. Role of the nitric oxide-cyclic GMP pathway in regulation of vaginal blood flow. Int J Impot Res 15 (2003) 355-361
6. Michaeli T., Bloom T.J., Martins T., et al. Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase deficient Saccharomyces cerevisiae. J Biol Chem 268 (1994) 12925-12932
7. Han P., Zhu X., and Michaeli T. Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A) mRNA in human skeletal muscle and heart. J Biol Chem 272 (1997) 16152-16157
8. Fisher A.D., Smith J.F., Pillar J.S., St. Denis S., and Cheng J.B. Isolation and characterization of PDE8A, a novel cAMP-specific phosphodiesterase. Biochem Biophys Res Commun 246 (1998) 570-577
9. Fisher A.D., Smith J.F., Pillar J.S., St. Denis S., and Cheng J.B. Isolation and characterization of PDE9A, a novel cGMP-specific phosphodiesterase. J Biol Chem 273 (1998) 15559-15564
10. Loughney K., Snyder P.B., Uher L., Rosman G.J., Ferguson K., and Florio V.A. Isolation and characterization of PDE10A, a novel human 3′.5′-cyclic nucleotide phosphodiesterase. Gene 234 (1999) 109-117
11. Fawcett L., Baxendale R., Stacey P., et al. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Natl Acad Sci USA 97 (2000) 3702-3707
12. Conti M., and Jin S.L. The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 63 (1999) 1-38
13. Essayan D.M. Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 108 (2001) 671-680
14. Rybulkin S.D., Yan C., Bornfeld K.E., and Beavo J.A. Cyclic GMP phosphodiesterase and smooth muscle function. Circ Res 93 (2003) 280-291
15. Maurice D.H., Palmer D., Tilley D.G., et al. Cyclic nucleotide phosphodiesterase activity, expression, and targeting cells in the cardiovascular system. Mol Pharmacol 64 (2003) 533-546
16. Holmquist F., Stief C.G., Jonas U., and Andersson K.E. Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit. Acta Physiol Scand 143 (1991) 299-304
17. Rajfer J., Aronson W.J., Bush P.A., Dorey F.J., and Ignarro L.J. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to non-adrenergic, non-cholinergic neurotransmission. N Engl J Med 326 (1992) 90-94
18. Truss M.C., Becker A.J., Djamillian M.H., Stief C.G., and Jonas U. Role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the diagnosis and treatment of erectile dysfunction. Urology 44 (1994) 553-556
19. Heaton J.P., Morales A., and Owen J. Topical glyceryltrinitrate causes measurable penile arterial dilatation in impotent men. J Urol 143 (1990) 729-731
20. Boolell M., Allen M.J., Balard S.A., et al. Sildenafil, an orally active type 5 cyclic GMP phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8 (1996) 47-52
21. Taher A. Cyclic nucleotide phosphodiesterase isoenzymes in human cavernous smooth muscle. World J Urol 15 (1997) 32-35
22. Sussman D.O. Pharmacokinetics, pharmacodynamics, and efficacy of phosphodiesterase type 5 inhibitors. J Am Osteopath Assoc 104 (2004) S11-S15
23. Kalsi J.S., and Kell P.D. Update on the oral treatments for male erectile dysfunction. Eur Acad Dermatol Venereol 18 (2004) 267-274
24. Morelli A., Filippi S., Mancina R., et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 145 (2004) 2253-2263
25. Moreland R.B., Goldstein I., and Traish A. Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 62 (1998) 309-318
26. Turko I.V., Ballard S.A., Francis S.H., and Corbin J.D. Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (type 5) by sildenafil and related compounds. Mol Pharmacol 56 (1999) 124-130
27. Corbin J.D., and Francis S.H. Molecular biology and pharmacology of PDE5-inhibitor therapy for erectile dysfunction. J Androl 24 (2003) S38-S41
28. Carson C.C., Burnett A.L., Levine L.A., and Neha A. The efficacy of sildenafil citrate (VIAGRA) in clinical populations: an update. Urology 60 (2002) 12-27
29. Fink H.A., McDonald R., Rutks I.R., Nelson D.B., and Wilt T.J. Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med 162 (2002) 1349-1360
30. Goldstein I., Lue T.F., Padma-Nathan H., Rosen R.C., Steers W.D., and Wicker P.A. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 338 (1998) 1397-1404
31. Küthe A., Mägert H.J., Ückert S., Forssmann W.G., Stief C.G., and Jonas U. Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. Eur Urol 38 (2000) 108-114
32. Padma-Nathan H. A four year update on the safety of sildenafil citrate (VIAGRA). Urology 60 (2002) 67-90
33. Bischoff E. Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events. Int J Impot Res 16 (2004) S34-S37
34. Blount M.A., Beasley A., Zoraghi R., et al. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol 66 (2004) 144-152
35. Saenz de Tejada I., Angulo J., Cuevas P., et al. The posphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res 13 (2001) 282-290
36. Bischoff E., Mondritzki T., Niewoehner U., Haning A., and Zimmer D. Vardenafil improved erections in rabbits longer than expected from plasma half-life. Int J Impot Res 14 (2002) S42
37. Young J., Auerbach S., and Prost H. Vardenafil, a new selective PDE5 inhibitor, significantly improved all IIEF domains and showed favourable safety profile in patients with erectile dysfunction over 12 weeks. J Urol 165 (2001) 224
38. Markou S., Perimenis P., Gyftopoulos K., Athanasopoulos A., and Barbialis G. Vardenafil (LEVITRA) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. Int J Impot Res 16 (2004) 470-478
39. Stief C., Porst H., Saenz de Tejada I., Ulbrich E., Beneke M., and and the Vardenafil Study Group. Sustained efficacy and tolerability with vardenafil over two years of treatment in men with erectile dysfunction. Int J Clin Pract 58 (2004) 230-239
40. Mazzu A., Nicholls A., and Zinny M. Vardenafil: a new highly selective PDE5 inhibitor, interacts minimally with nitroglycerin in healthy middle-aged subjects. Int J Impot Res 13 (2001) S64
41. Thadani U., and Mazzu A. Exercise-induced ischemia was not adversely affected by vardenafil during exercise stress test in men with coronary artery disease. Eur Urol Suppl 1 1 (2002) 151
42. Eardly I., and Cartledge J. Tadalafil (CIALIS) for men with erectile dysfunction. Int J Clin Pract 56 (2002) 300-304
43. Yuasa K., Kotera J., Fujishige K., Michibata H., Sasaki T., and Omori K. Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. J Biol Chem 275 (2000) 31469-31479
44. Brock G.B., McMahon C.G., Chen K.K., et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 168 (2002) 1332-1336
45. Porst H., Patma-Nathan H., Guiliano F., Anglin G., Varanese L., and Rosen R. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized, controlled study. Urology 62 (2003) 121-125
46. Guiliano F., and Varanese L. Tadalafil: a novel treatment for erectile dysfunction. Eur Heart J 4 (2002) H24-H31
47. Gbekor E., Betheil S., Fawcett L., et al. Selectivity of sildenafil and other phosphodiesterase type 5 (PDE5) inhibitors against all human phosphodiesterase families. Eur Urol Suppl 1 1 (2001) 63
48. Emmick J.T., Stuewe S.R., and Mitchell M. Overview of the cardiovascular effects of tadalafil. Eur Heart J 4 (2002) H32-H47
49. Ottensen B., Wagner G., Virag R., and Fahrenkrug J. Penile erection: possible role for vasoactive intestinal polypeptide as a neurotransmitter. Br J Med 288 (1984) 9-11
50. Porst H. The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol 155 (1996) 802-815
51. Cahn D., Melman A., Valcic M., and Christ G.J. Forskolin: a promising new adjunct to intracavernous pharmacotherapy. J Urol 155 (1997) 1789-1794
52. Rajasekaran M., Sikka S., Hellstrom W., and Doherty P. Evidence for the presence of the type 4 phosphodiesterase in isolated human cavernosal smooth muscle cells. Int J Impot Res 10 (1998) S55
53. Küthe A., Wiedenroth A., Mägert H.J., Ückert S., Forssmann W.G., Stief C.G., et al. Expression of different phosphodiesterase genes in human cavernous smooth muscle. J Urol 165 (2001) 280-283
54. Stief C.G., Taher A., Truss M.C., et al. Die phosphodiesterase-Isoenzyme des humanen corpus cavernosum penis und deren funktionelle bedeutung. Akt Urol 26 (1995) 22-24
55. Stief C.G., Ückert S., Becker A.J., Truss M.C., and Jonas U. Effects of specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. J Urol 159 (1998) 1390-1393
56. Ückert S., Hedlund P., Waldkirch E., et al. Interactions between cGMP- and cAMP-pathways are involved in the regulation of penile smooth muscle tone. World J Urol 22 (2004) 261-266
57. Guay D., Hamel P., Blouin M., et al. Discovery of L-791.943: a potent, selective, non-emetic and orally active phosphodiesterase 4 inhibitor. Bioorg Med Chem Lett 12 (2002) 1457-1461
58. Silver P.J., Dundore R.L., Bode D.C., et al. Cyclic GMP potentiation by WIN 58237, a novel cyclic nucleotide phosphodiesterase inhibitor. J Pharmacol Exp Ther 271 (1997) 1143-1149
59. Salinas Casado J., Virseda Chamorro M., Samblas Garcia R., et al. Neurobiology of ejaculation and orgasm disorders. Arch Esp Urol 51 (1998) 265-268
60. Machtens S., Ückert S., Stanarius A., et al. Ist die sekretion der humanen samenblase durch stickoxid (NO) reguliert?. J Urol Urogynäkol 4 (2001) 15-22
61. Machtens S., Ückert S., Stief C.G., Tsikas D., Frölich J.C., and Jonas U. Effects of various nitric oxide-donating drugs on adrenergic tension of human seminal vesicles in vitro. Urology 61 (2003) 479-483
62. Ückert S., Stanarius A., Stief C.G., Wolf G., Jonas U., and Machtens S. Immunocytochemical distribution of nitric oxide synthase in the human seminal vesicle: a light- and electron microscopical study. Urol Res 31 (2003) 262-266
63. Heuer O., Ückert S., Machtens S., et al. Effects of various nitric oxide donating agents on the contractility and cyclic nucleotide turnover of human seminal vesicles in vitro. Urology 59 (2002) 958-962
64. Abdel-Hamid I.A. Phosphodiesterase 5 inhibitors in rapid ejaculation: potential use and possible mechanisms of action. Drugs 64 (2004) 13-26
65. Rosen R.C., and McKenna K.E. PDE5 inhibition and sexual response: pharmacological mechanisms and clinical outcomes. Annu Rev Sex Res 13 (2002) 36-88
66. Ückert S., Scheller F., Jonas U., and Basrafshan S. Functional responses of isolated human seminal vesicle tissue to selective phosphodiesterase inhibitors. J Sex Med (2006) 57
67. Guess H.A. Epidemiology and natural history of benign prostatic hyperplasia. Urol Clin North Am 22 (1995) 247-261
68. Chiricos T.N., and Sanford E. Cost consequences of surveillance, medical management or surgery for benign prostatic hyperplasia. J Urol 155 (1996) 1311-1316
69. Jacobsen S.J., Guess H.A., Panser L., et al. A population-based study of health care-seeking behaviour for treatment of urinary symptoms. Arch Fam Med 2 (1993) 729-735
70. Hieble J.R., and Ruffolo Jr. R.R. The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hyperplasia: an overview. Pharmacol Res 33 (1996) 145-160
71. Andersen J.T., Ekman P., Wolf H., et al. Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. Urology 46 (1995) 631-637
72. Roehrborn C.G., Marks L.S., Fenter T., et al. Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 63 (2004) 709-715
73. Lu-Yao G.L., Barry M.J., Chang C.H., Wasson J.H., and Wennberg J.E. Transurethral resection of the prostate among Medicare beneficiaries in the United States: time trends and outcomes. Urology 44 (1994) 692-699
74. Gingel J.C., Knonagel H., Kurth K.H., Tunn U.W., and and the Schering 90.062 Study Group. Placebo-controlled, double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia. J Urol 154 (1995) 399-401
75. Denis L., Pagano F., Nonis A., Robertson C., Romano P., and Boyle P. Double-blind, placebo-controlled trial to assess the efficacy and tolerability of mepartricin in the treatment of BPH. Prostate 37 (1998) 246-252
76. ®) bei Benigner Prostatahyperplasie: Ergebnisse einer Anwendungsbeobachtung. J Urol Urogynäkol 4 (2000) 13-19
77. Raschack M., Göck S., Unger L., et al. LU 302 872 and its racemate show balanced endothelin-A/B receptor affinity, high oral activity, and inhibit human prostate contractions. J Cardiovasc Pharmacol 31 (1998) S241-S244
78. Drescher P., Eckert R.E., and Madsen P.O. Smooth muscle contractility in prostatic hyperplasia: role of cyclic adenosine monophosphate. Prostate 25 (1994) 76-80
79. Takeda M., Tang R., Shapiro E., Burnett A.L., and Lepor H. Effects of nitric oxide on human and canine prostates. Urology 45 (1995) 440-446
80. Bloch W., Klotz T., Loch C., Schmidt G., Engelmann U., and Addicks K. Distribution of nitric oxide synthase implies a regulation of circulation, smooth muscle tone, and secretory function in the human prostate by nitric oxide. Prostate 33 (1997) 1-8
81. Ückert S., Küthe A., Jonas U., and Stief C.G. Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol 166 (2001) 2484-2490
82. Ückert S., Hedlund P., Stief C.G., Andersson K.E., and Jonas U. Histochemische distribution cAMP- und cGMP-spezifischer phosphodiesterase-Isoenzyme in der humanen prostata. Wiener Klin Wochenschr 115 (2003) 18
83. Sairam K., Kulinskaya E., McNicholas T.A., Boustead G.B., and Hanbury D.C. Sildenafil influences lower urinary tract symptoms. BJU Int 90 (2002) 836-839
84. Ückert S., Hedlund P., Oelke M., Stief C.G., Andersson K.E., and Jonas U. Immunohistochemical presence of phosphodiesterase 11A in the human prostate. J Urol 171 (2004) 352
85. Bang Y.J., Pirnia F., Fang W.G., et al. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. Proc Natl Acad Sci USA 91 (2003) 5330-5334
86. Goto T., Matsushima H., Hasuya Y., et al. The effect of papaverine on morphologic differentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells. Int J Urol 6 (1999) 314-319
87. Liu L., Li H., Underwood T., et al. Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells. J Pharmacol Exp Ther 299 (2001) 583-592
88. 2-terminal kinase 1. Clin Cancer Res 6 (2000) 4136-4141
89. Andersson K.E., Chapple C., and Wein A. The basis for drug treatment of the overactive bladder. World J Urol 19 (2001) 294-298
90. Sellers D.J., Chapple C.R., and Chess-williams R. Potential therapeutic targets for the treatment of the overactive bladder. World J Urol 19 (2001) 307-311
91. Truss M.C., Ückert S., Stief C.G., Kuczyk M.A., and Jonas U. Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle: I. Identification and characterization. Urol Res 24 (1996) 123-128
92. Truss M.C., Ückert S., Stief C.G., Kuczyk M.A., and Jonas U. 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
93. Ückert S., Seemann C., Stief C.G., et al. Funktionelle in vitro-effekte cAMP/cGMP-modulierender pharmaka am humanen detrusormuskel. J Urol Urogynäkol 1 (2002) 7-14
94. Truss M.C., Stief C.G., Ückert S., et al. Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside. World J Urol 19 (2001) 344-350
95. Hartmann M. Urologische notfallsituationen. In: Altwein J.E., and Rübben H. (Eds). Urologie (1991), Enke Verlag, Stuttgart 395-424
96. Taher A., Schulz-Knappe P., Meyer M., et al. Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro. World J Urol 12 (1994) 286-291
97. Kühn R., Ückert S., Stief C.G., et al. Relaxation of human ureteral smooth muscle in vitro by modulation of cyclic nucleotide dependent pathways. Urol Res 28 (2000) 110-115
98. Becker A.J., Stief C.G., Meyer M., Truss M.C., Forssmann W.G., and Jonas U. The effect of the specific phosphodiesterase 4 inhibitor rolipram on the ureteral peristalsis in vitro and in vivo. J Urol 160 (1998) 920-925
99. Lauman E., Paik A., and Rosen R. Sexual dysfunction in the United States: prevalence and predictors. JAMA 281 (1999) 537-544
100. Berman J.R., and Goldstein R. Female sexual dysfunction. Urol Clin North Am 28 (2001) 94-143
101. Berman J.R., and Bassuk J. Physiology and pathophysiology of female sexual function and dysfunction. World J Urol 20 (2002) 111-118
102. Khan M.A., Thompson C.S., Mumtaz F.H., Mikhailidis D.P., and Morgan R.J. Urological aspects of female sexual dysfunction. Urol Int 65 (2000) 1-8
103. Burnett A.L., Calvin D.C., Silver R.I., Peppas D.S., and Docimo S.G. Immunohistochemical description of nitric oxide synthase isoforms in human clitoris. J Urol 158 (1997) 75-78
104. Park K., Moreland R.B., Goldstein I., Atala A., and Traish A. Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle. Biochem Biophys Res Comm 49 (1998) 612-617
105. Oelke M., Ückert S., Hedlund P., Stief C.G., Jonas U., and Andersson K.E. Immunohistochemical presence of cyclic AMP- and cyclic GMP-phosphodiesterase isoenzymes in the human clitoris. Int J Impot Res 15 (2003) S178
106. Ückert S., Oelke M., Hedlund P., et al. Detection of phosphodiesterase isoenzymes 1, 2, 10 and 11 in the human clitoris by means of molecular biology and immunohistochemistry. Eur Urol Suppl 3 2 (2004) 64
107. Ückert S., Oelke M., Waldkirch E., et al. Cyclic adenosine monophosphate and cyclic guanosine monophosphate-phospho-diesterase isoenzymes in the human vagina: relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide containing nerves. Urology 65 (2005) 604-610
108. D'Amati G., Di Gioia C.R.T., Giordano D., Giorgi M., Dolci S., and Jannini E.A. Type 5 phosphodiesterase expression in the human vagina. Urology 60 (2002) 191-195
109. Caruso S., Intelisano G., Lupo L., and Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, crossover, placebo-controlled study. BJOG 108 (2001) 623-628
110. Berman J.R., Berman L.A., Lin H., et al. Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder. J Sex Marital Ther 27 (2001) 411-420
111. Berman J.R., Berman L.A., Toler S.M., Gill J., Haughie S., and and the Sildenafil Study Group. Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo-controlled study. J Urol 170 (2003) 2333-2338
112. Dasgupta R., Wiseman O.J., Kanabar G., Fowler C.J., and Mikol D.D. Efficacy of sildenafil in the treatment of female sexual dysfunction due to multiple sclerosis. J Urol 171 (2004) 1189-1193
113. Sipski M.L., Rosen R.C., Alexander C.J., and Hamer R.M. Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury. Urology 55 (2000) 812-815
114. Kaplan S.A., Rodolfo R.B., Kohn I.J., Ikeguchi I.F., Laor E., Te A.E., et al. Safety and efficacy of sildenafil in postmenopausal women with sexual dysfunction. Urology 53 (1999) 481-486
115. Basson R., and Brotto L.A. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial. BJOG 110 (2003) 1014-1024
116. Conti M., and Jin S.L. The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 63 (1999) 1-38
117. Lin C.S., Lau A., Tu R., and Lue T.R. Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Comm 268 (2000) 628-635
118. Bai W.J., Hou S.K., Wang X.F., et al. The effects of antisense oligodeoxynucleotide on the cyclic nucleotide monophosphates in smooth muscle cells of human corpus cavernosum. Zhongua Nan Ke Xue 8 (2002) 88-91
119. Hedlund P. Genes and erectile function. Curr Opin Urol 13 (2003) 397-403