PDE5A

Summary

Gene Symbol: PDE5A
Description: phosphodiesterase 5A
Alias: CGB-PDE, CN5A, PDE5, cGMP-specific 3',5'-cyclic phosphodiesterase, cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase, cGMP-specific phosphodiesterase PDE5A2, cGMP-specific phosphodiesterase type 5A, phosphodiesterase 5A, cGMP-specific, phosphodiesterase isozyme 5
Species: human

Top Publications

  1. ncbi Substrate- and kinase-directed regulation of phosphorylation of a cGMP-binding phosphodiesterase by cGMP
    M K Thomas
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615
    J Biol Chem 265:14971-8. 1990
  2. pmc PDE5 is converted to an activated state upon cGMP binding to the GAF A domain
    Sergei D Rybalkin
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    EMBO J 22:469-78. 2003
  3. pmc Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice
    Peter Pokreisz
    Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium
    Circulation 119:408-16. 2009
  4. pmc Oxidative stress regulates left ventricular PDE5 expression in the failing heart
    Zhongbing Lu
    Cardiovascular Division, University of Minnesota, Minneapolis, MN 55455, USA
    Circulation 121:1474-83. 2010
  5. pmc Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling
    Florian Mullershausen
    Abteilung für Pharmakologie und Toxikologie, Medizinische Fakultat, Ruhr Universitat Bochum, MA N1 43, Universitaetsstr 150, 44780 Bochum, Germany
    J Cell Biol 160:719-27. 2003
  6. ncbi Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries--immunohistochemical distribution and functional significance
    Eginhard Waldkirch
    Department of Urology, Hannover Medical School, 30625, Hannover, Germany
    World J Urol 23:405-10. 2005
  7. doi PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries
    António José Santos-Silva
    Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Av Infante D Henrique, 6200 506 Covilha, Portugal
    Eur J Pharmacol 582:102-9. 2008
  8. doi Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia
    Christina Luong
    Department of Pediatrics, Women and Children Health Research Institute, Cardiovascular Research Group, University of Alberta, Edmonton, Canada
    Circulation 123:2120-31. 2011
  9. doi Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus
    Rodrigo O Capel
    Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas UNICAMP, Campinas, SP, Brazil
    J Sex Med 8:1616-25. 2011
  10. ncbi Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues
    Stefan Uckert
    Hannover Medical School Department of Urology, Hannover, Germany, and IPF Pharmaceuticals GmbH Urological Research Unit, Hannover, Germany
    J Sex Med 4:1604-9. 2007

Research Grants

  1. cGMP Phosphodiesterase Inhibitors in a Mouse Model of Duchenne Muscular Dystrophy
    STANLEY FROEHNER; Fiscal Year: 2009
  2. DAVID ALAN KASS; Fiscal Year: 2016
  3. Rick H Cote; Fiscal Year: 2016
  4. Structure and Regulation of the GPCR-G Protein Interactions in the Visual System
    ARNOLD EINO RUOHO; Fiscal Year: 2011
  5. A Novel HTS Cell-Based Assay For Cyclic GMP
    Gary Piazza; Fiscal Year: 2007
  6. NITRIC OXIDE AND IN VIVO BRAIN ARTERIOLAR RELAXATION
    Dale Pelligrino; Fiscal Year: 2004
  7. REGULATION OF PDE 5 IN HUMAN PENILE SMOOTH MUSCLE CELLS
    Noel Kim; Fiscal Year: 2001
  8. Peptide Therapy for Pulmonary Arterial Hypertension
    Jawaharlal M Patel; Fiscal Year: 2013
  9. Planning a Multicenter Trial of PDE5A Inhibition for Duchenne Muscular Dystrophy
    Ronald G Victor; Fiscal Year: 2012
  10. Nancy J Brown; Fiscal Year: 2014

Detail Information

Publications264 found, 100 shown here

  1. ncbi Substrate- and kinase-directed regulation of phosphorylation of a cGMP-binding phosphodiesterase by cGMP
    M K Thomas
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615
    J Biol Chem 265:14971-8. 1990
    ..Such regulation would greatly increase the selectivity of the phosphorylation of cG-BPDE and would represent a unique mechanism of action of a cyclic nucleotide or other second messenger...
  2. pmc PDE5 is converted to an activated state upon cGMP binding to the GAF A domain
    Sergei D Rybalkin
    Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
    EMBO J 22:469-78. 2003
    cGMP-specific, cGMP-binding phosphodiesterase (PDE5) regulates such physiological processes as smooth muscle relaxation and neuronal survival...
  3. pmc Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice
    Peter Pokreisz
    Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium
    Circulation 119:408-16. 2009
    Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role in left ventricular (LV) failure remains incompletely understood...
  4. pmc Oxidative stress regulates left ventricular PDE5 expression in the failing heart
    Zhongbing Lu
    Cardiovascular Division, University of Minnesota, Minneapolis, MN 55455, USA
    Circulation 121:1474-83. 2010
    Phosphodiesterase type 5 (PDE5) inhibition has been shown to exert profound beneficial effects in the failing heart, suggesting a significant role for PDE5 in the development of congestive heart failure (CHF)...
  5. pmc Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling
    Florian Mullershausen
    Abteilung für Pharmakologie und Toxikologie, Medizinische Fakultat, Ruhr Universitat Bochum, MA N1 43, Universitaetsstr 150, 44780 Bochum, Germany
    J Cell Biol 160:719-27. 2003
    ..within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred...
  6. ncbi Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries--immunohistochemical distribution and functional significance
    Eginhard Waldkirch
    Department of Urology, Hannover Medical School, 30625, Hannover, Germany
    World J Urol 23:405-10. 2005
    ....
  7. doi PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries
    António José Santos-Silva
    Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Av Infante D Henrique, 6200 506 Covilha, Portugal
    Eur J Pharmacol 582:102-9. 2008
    ..umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected...
  8. doi Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia
    Christina Luong
    Department of Pediatrics, Women and Children Health Research Institute, Cardiovascular Research Group, University of Alberta, Edmonton, Canada
    Circulation 123:2120-31. 2011
    ..Phosphodiesterase type 5 (PDE5) limits the effects of NO by inactivation of cyclic GMP...
  9. doi Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus
    Rodrigo O Capel
    Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas UNICAMP, Campinas, SP, Brazil
    J Sex Med 8:1616-25. 2011
    ..Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown...
  10. ncbi Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues
    Stefan Uckert
    Hannover Medical School Department of Urology, Hannover, Germany, and IPF Pharmaceuticals GmbH Urological Research Unit, Hannover, Germany
    J Sex Med 4:1604-9. 2007
    The use of inhibitors of phosphodiesterase 5 (PDE5) has been suggested to treat symptoms of female sexual dysfunction (FSD)...
  11. doi Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue
    Stefan Uckert
    Department of Urology, Hannover Medical School, Hannover, Germany
    Urology 71:526-30. 2008
    ..the mechanism of action of phosphodiesterase (PDE) inhibitors on the human prostate, the effects of PDE4 and PDE5 inhibitors on the tension induced by norepinephrine (NE) and on the intracellular levels of cyclic nucleotides in ..
  12. ncbi Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system
    Lars S Kruse
    Department of Neurology, Glostrup Hospital, Nordre Ringvej 57, Denmark
    Neurosci Lett 404:202-7. 2006
    ..For comparison, rat aorta and mesenteric artery were analysed. PDE3A, PDE3B, and PDE5A mRNA were detected in all tissues examined except for PDE3A mRNA in dura mater and the trigeminal ganglion...
  13. ncbi Experimental studies on guanosine 3',5'-cyclic monophosphate levels and airway responsiveness of the novel phosphodiesterase type 5 inhibitor SR 265579 in guinea-pigs
    Z Kapui
    Biological Research Department, Chinoin Pharmaceutical and Chemicals Works, Budapest, Hungary
    Arzneimittelforschung 49:685-93. 1999
    ..SR 265579), a potent inhibitor of guanosine 3',5'-cyclic monophosphate (cyclic GMP) phosphodiesterase (PDE5), was examined regarding its specificity toward the other cyclic nucleotide phosphodiesterases, the effect on ..
  14. doi Effects of phosphodiesterase inhibitors on the contractile responses of isolated human seminal vesicle tissue to adrenergic stimulation
    Stefan Uckert
    Division of Surgery, Department of Urology, Hannover Medical School, Hannover, Germany
    J Sex Med 6:408-14. 2009
    It has been suggested that the capability of the phosphodiesterase 5 (PDE5) inhibitor sildenafil citrate (VIAGRA) to retard the ejaculatory response may include modulation of the contraction of seminal vesicle (SV) smooth muscle...
  15. doi Phosphodiesterase inhibitors and the eye
    Nathan M Kerr
    Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    Clin Experiment Ophthalmol 37:514-23. 2009
    Phosphodiesterase type 5 (PDE5) inhibitors are effective oral treatments for erectile dysfunction and have become one of the most widely prescribed medications worldwide...
  16. ncbi Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions
    Robert A Kloner
    Heart Institute, Good Samaritan Hospital, Keck School of Medicine, University of Southern California, Los Angeles, CA 90017, USA
    Am J Cardiol 96:42M-46M. 2005
    Currently, 3 phosphodiesterase 5 (PDE5) inhibitor agents are available worldwide for the treatment of erectile dysfunction (ED): sildenafil, vardenafil, and tadalafil...
  17. doi Effect of sildenafil on middle-aged sexually active males with no erectile complaints: a randomized placebo-controlled double-blind study
    Ilan Gruenwald
    Neuro urology unit, Rambam Health Care Campus and the Technion Faculty of Medicine, Haifa, Israel
    Eur Urol 55:969-76. 2009
    In clinical practice, we commonly encounter sexually healthy males who use phosphodiesterase type 5 (PDE5) inhibitors and report a beneficial effect to their sex life.
  18. doi Combination of doxazosin and sildenafil exerts an additive relaxing effect compared with each compound alone on human cavernosal and prostatic tissue
    Stephanie Oger
    Pelvipharm, Orsay Parc, Orsay, France
    J Sex Med 6:836-47. 2009
    Phosphodiesterase 5 inhibitors (PDE5) such as sildenafil are first-line treatment for erectile dysfunction (ED)...
  19. doi Phosphodiesterase type 5 regulation in the penile corpora cavernosa
    Ching Shwun Lin
    Knuppe Molecular Urology Laboratory, University of California, Department of Urology, San Francisco, CA 94115, USA
    J Sex Med 6:203-9. 2009
    Penile detumescence depends on the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterase type 5 (PDE5)...
  20. pmc Concerted regulation of cGMP and cAMP phosphodiesterases in early cardiac hypertrophy induced by angiotensin II
    Walid Mokni
    CNRS UMR 7213, Biophotonique et Pharmacologie, Faculte de Pharmacie, Universite de Strasbourg, Illkirch, France
    PLoS ONE 5:e14227. 2010
    ..130% for PDE1; +76% for PDE2; +113% for PDE5) and associated with increased expressions for PDE1A, PDE1C and PDE5A. The cGMP-PDE1 activation by Ca(2+)/CaM was reduced. BNP expression was increased by 3...
  21. ncbi PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation
    Anna R Hemnes
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 850, Baltimore, MD 21205, USA
    Am J Physiol Lung Cell Mol Physiol 294:L24-33. 2008
    ..lung disease-associated pulmonary hypertension, and this process can be abrogated by phosphodiesterase type 5 (PDE5) inhibition to improve pulmonary vascular remodeling and right ventricular function...
  22. ncbi Effectiveness of sildenafil citrate (Viagra) and tadalafil (Cialis) on sexual responses in Saudi men with erectile dysfunction in routine clinical practice
    Syed Tabrez Ali
    Department of Physiology, Faculty of Medicine, Umm Al Qura University, Makkah, Saudi Arabia
    Pak J Pharm Sci 21:275-81. 2008
    ..Sildenafil citrate (Viagra) is a potent inhibitor of the electrolytic enzyme type V phosphodiesterase (PDE5), in the corpus cavernosum and therefore increases the penile response to sexual stimulation...
  23. doi [Erectile dysfunction after radical prostatectomy : patient information, contact persons, postoperative proerectile therapy]
    S Kaufmann
    Klinik für Urologie und Kinderurologie, Universitatsklinikum Schleswig Holstein, Campus Kiel, Campus Kiel, Arnold Heller Str 7, 24105, Kiel, Deutschland
    Urologe A 49:525-9. 2010
    ..the patients prior to the intervention about the risk of ED, which individuals the patients discuss this issue with, and whether the patients preoperatively consider use of a PDE5 inhibitor for proerectile therapy after the operation.
  24. ncbi Role of nitric oxide/cyclic GMP pathway in regulating spontaneous excitations in detrusor smooth muscle of the guinea-pig bladder
    Yoshimasa Yanai
    Department of Nephro urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    Neurourol Urodyn 27:446-53. 2008
    ..We have investigated the effects of NO donors and phosphodiesterase-5 (PDE5) inhibition on spontaneous excitations in DSM.
  25. doi Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: a critical analysis of the basic science rationale and clinical application
    Konstantinos Hatzimouratidis
    2nd Department of Urology, Aristotle University, Thessaloniki, Greece
    Eur Urol 55:334-47. 2009
    ..Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy ..
  26. ncbi Phosphodiesterase inhibitors in the treatment of erectile dysfunction in spinal cord-injured men
    J M Soler
    Centre Bouffard Vercelli, Laboratoire d urodynamique et de sexologie, Cerbère, France
    Spinal Cord 45:169-73. 2007
    ..Open, before-after study...
  27. doi Effects of phosphodiesterase inhibitors on the inflammatory response of endothelial cells stimulated by myeloperoxidase-modified low-density lipoprotein or tumor necrosis factor alpha
    Thierry Roumeguere
    Laboratory of Experimental Medicine, Unit 222, CHU Charleroi, Free University of Brussels, Montigny le Tilleul, Belgium
    Eur Urol 57:522-8. 2010
    Sildenafil, vardenafil, and tadalafil are phosphodiesterase type 5 inhibitors (PDE5-Is) usually used in the treatment of erectile dysfunction (ED)...
  28. ncbi Successful withdrawal of oral long-acting nitrates to facilitate phosphodiesterase type 5 inhibitor use in stable coronary disease patients with erectile dysfunction
    Graham Jackson
    Guy s and St Thomas Hospital Cardiothoracic Centre, London, United Kingdom
    J Sex Med 2:513-6. 2005
    Vascular disease is the most common cause of male erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors are effective in up to 80% of men but are contraindicated in the presence of oral nitrates, because of a potentially ..
  29. ncbi Time course of the interaction between tadalafil and nitrates
    Robert A Kloner
    The Heart Institute, Good Samaritan Hospital, Cardiovascular Division, Keck School of Medicine, University of Southern California, Los Angeles, California 90017, USA
    J Am Coll Cardiol 42:1855-60. 2003
    This study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t(1/2)) of 17.5 h.
  30. ncbi Phosphodiesterase 5 inhibitors in the treatment of premature ejaculation
    W F Wang
    Department of Urology, Hainan Provincial People s Hospital, Haikou, Hainan Province, China
    Int J Androl 29:503-09. 2006
    To date, there is no FDA-approved therapy for premature ejaculation (PE). Recently, phosphodiesterase 5 inhibitors (PDE5-Is) have been demonstrated to have encouraging results in the treatment of PE by a few studies...
  31. ncbi Molecular modeling studies of pyridopurinone derivatives--potential phosphodiesterase 5 inhibitors
    P Srivani
    Molecular Modeling Group, Organic Chemical Sciences, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
    J Mol Graph Model 26:378-90. 2007
    ..QSAR) and docking studies were carried out on a series of pyridopurinones, to model their phosphodiesterase 5 (PDE5) inhibitory activities...
  32. ncbi Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects
    C Foresta
    Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
    Eye (Lond) 22:144-9. 2008
    We tested the effect of two phosphodiesterase type-5 (PDE5) inhibitors, sildenafil and tadalafil, on ophthalmic artery (OA) blood flow velocity and investigated the presence of the PDE5 enzyme on human retinal tissue in comparison with ..
  33. ncbi Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity
    F Dimitriadis
    Department of Urology, Ioannina University School of Medicine, Ioannina 45110, Greece
    Asian J Androl 10:115-33. 2008
    The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte...
  34. pmc Effect of the phosphodiesterase 5 inhibitors sildenafil, tadalafil and vardenafil on rat anococcygeus muscle: functional and biochemical aspects
    Haroldo A Toque
    Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas, Sao Paulo, Brazil
    Clin Exp Pharmacol Physiol 36:358-66. 2009
    ..The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2...
  35. doi Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling
    Stefan Schafer
    Cardiology Research, Bayer Schering Pharma, Aprather Weg 18, 42096 Wuppertal, Germany
    Cardiovasc Res 82:30-9. 2009
    Inhibition of phosphodiesterase 5 (PDE5) decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension...
  36. doi The ontogenetic expression pattern of type 5 phosphodiesterase correlates with androgen receptor expression in rat corpora cavernosa
    Eleonora Carosa
    Course of Endocrinology and Medical Sexology, Department of Experimental Medicine, University of L Aquila, L Aquila, Italy
    J Sex Med 6:388-96. 2009
    ..The mechanisms controlling erection in animals and in humans are mainly age-dependent. However, the ontogenesis of the biochemical machinery of erection is largely unknown...
  37. ncbi Microarray analysis of gene expression profile in the corpus cavernosum of hypercholesterolemic rats after chronic treatment with PDE5 inhibitor
    Han Gook Jung
    Research Institutes of Dong A Pharmaceutical Company, 47 5 Sanggal, Kiheung, Youngin, Kyunggi 449 905, Republic of Korea
    Life Sci 80:699-708. 2007
    ..of hypercholesterolemia-related ED and to investigate the effects of Udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on gene expression, we performed microarray gene expression analysis via gene discovery methods using ..
  38. ncbi [3H]sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous, and stimulated by cGMP
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, TN 37232 0615, USA
    Mol Pharmacol 63:1364-72. 2003
    ..acting as a nonhydrolyzable analog of cGMP and competing with this nucleotide for catalysis by phosphodiesterase-5 (PDE5), but the characteristics of direct binding of radiolabeled sildenafil to PDE5 have not been determined...
  39. ncbi cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism
    Eiki Takimoto
    Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
    Circ Res 96:100-9. 2005
    ..cGMP is also catabolically regulated by phosphodiesterase 5A (PDE5A)...
  40. pmc Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism
    Hunter C Champion
    Department of Cardiology, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 102:1661-6. 2005
    ..We investigated the role of downstream guanylate cyclase and phosphodiesterase type 5 (PDE5A) expression and function in mediating these responses in eNOS-/- and nNOS-/-, eNOS-/- mice...
  41. ncbi The role of phosphodiesterase type 5 inhibitors in the management of premature ejaculation: a critical analysis of basic science and clinical data
    Juza Chen
    Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Eur Urol 52:1331-9. 2007
    To assess the usefulness of the phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of premature ejaculation (PE) and to describe possible mechanisms to explain their effect.
  42. ncbi Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors
    Roya Zoraghi
    Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Biochemistry 46:13554-63. 2007
    The molecular bases for phosphodiesterase 5 (PDE5) catalytic-site affinity for cyclic guanosine monophosphate (cGMP) and potency of inhibitors are poorly understood...
  43. ncbi Resistance to the nitric oxide/cyclic guanosine 5'-monophosphate/protein kinase G pathway in vascular smooth muscle cells from the obese Zucker rat, a classical animal model of insulin resistance: role of oxidative stress
    I Russo
    Diabetes Unit, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, 10043 Orbassano TO, Italy
    Endocrinology 149:1480-9. 2008
    ..and cGMP ability to induce, via PKG, vasodilator-stimulated phosphoprotein (VASP) phosphorylation at serine 239 and PDE5 activity; 3) protein expression of sGC, PKG, total VASP, and PDE5; 4) superoxide anion concentrations and ability ..
  44. ncbi Differential effects of the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, and tadalafil in rat aorta
    Cleber E Teixeira
    Department of Physiology, Medical College of Georgia, Augusta, 30912 3000, USA
    J Pharmacol Exp Ther 316:654-61. 2006
    Presumably, the vasorelaxant properties of phosphodiesterase type 5 (PDE5) inhibitors are similar in isolated blood vessels...
  45. ncbi In vitro effects of PDE5 inhibitors sildenafil, vardenafil and tadalafil on isolated human ureteral smooth muscle: a basic research approach
    Christian Gratzke
    Department of Urology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistr 15, 81377, Munich, Germany
    Urol Res 35:49-54. 2007
    ..The aim of the present study was to evaluate the functional effects of PDE5 inhibitors sildenafil (Sil), vardenafil (Var) and tadalafil (Tad), as well as nitric oxide (NO)-donating agent ..
  46. doi Pharmacological characterization of a novel phosphodiesterase type 5 (PDE5) inhibitor lodenafil carbonate on human and rabbit corpus cavernosum
    Haroldo A Toque
    Department of Pharmacology, UNICAMP, Campinas, SP, 13081 970, Brazil
    Eur J Pharmacol 591:189-95. 2008
    ..Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong the NO effects by inhibiting cGMP breakdown...
  47. pmc Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension
    Reshma S Baliga
    Centre for Clinical Pharmacology, University College London, The Rayne Building, 5 University Street, London WC1E 5JJ, UK
    Am J Respir Crit Care Med 178:861-9. 2008
    Phosphodiesterase 5 (PDE5) inhibitors (e.g., sildenafil) are selective pulmonary vasodilators in patients with pulmonary arterial hypertension...
  48. pmc A placebo-controlled study of sildenafil effects on cognition in schizophrenia
    Donald C Goff
    Department of Psychiatry, MGH Schizophrenia Program, Freedom Trail Clinic, Massachusetts General Hospital, Harvard Medical School, 25 Staniford St, 2nd Floor, Boston, MA, 02114, USA
    Psychopharmacology (Berl) 202:411-7. 2009
    Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and ..
  49. doi The role of PDE5 inhibitors in heme oxygenase-cGMP relationship in rat cavernous tissues
    M Talaat Abdel Aziz
    Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
    J Sex Med 5:1636-45. 2008
    ..Heme oxygenase (HO) enzyme catalyzes oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO shares many properties with nitric oxide (NO) including the activation of soluble guanyl cyclase...
  50. doi Randomized phase II trial evaluation of erectile function after attempted unilateral cavernous nerve-sparing retropubic radical prostatectomy with versus without unilateral sural nerve grafting for clinically localized prostate cancer
    John W Davis
    Department of Urology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Eur Urol 55:1135-43. 2009
    ..Nonrandomized studies of unilateral nerve-sparing (UNS) radical prostatectomy (RP) have reported improved recovery of erectile function if the sacrificed cavernous nerve is reconstructed with a sural nerve graft (SNG)...
  51. doi Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries
    Javier Angulo
    Departamento de Investigacion, Hospital Ramon y Cajal, Madrid, Spain
    J Sex Med 7:758-68. 2010
    Diabetic men with erectile dysfunction (ED) are less responsive to therapy with type 5 phosphodiesterase (PDE5) inhibitors...
  52. pmc Allosteric-site and catalytic-site ligand effects on PDE5 functions are associated with distinct changes in physical form of the enzyme
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, United States
    Cell Signal 21:1768-74. 2009
    Native phosphodiesterase-5 (PDE5) homodimer contains distinct non-catalytic cGMP allosteric sites and catalytic sites for cGMP hydrolysis. Purified recombinant PDE5 was activated by pre-incubation with cGMP...
  53. doi Does educational status affect a patient's behavior toward erectile dysfunction?
    Andrea Salonia
    Department of Urology, University Vita Salute San Raffaele, Scientific Institute H San Raffaele, Milan, Italy
    J Sex Med 5:1941-8. 2008
    ..rarely as a potential factor affecting the behavior of patients with new onset erectile dysfunction (ED) toward seeking first medical help and subsequent compliance with prescribed phosphodiesterase type 5 inhibitor (PDE5) therapy.
  54. doi Co-possession of phosphodiesterase type-5 inhibitors (PDE5-I) with nitrates
    Li Ling Chang
    IMS Health, Inc, Plymouth Meeting, PA 19422, USA
    Curr Med Res Opin 26:1451-9. 2010
    Estimate the proportion of phosphodiesterase type-5 inhibitor (PDE5-I) patients who co-possess nitrates and compare the proportion of tadalafil patients dispensed nitrates to a matched control group...
  55. doi Vardenafil can improve continence recovery after bilateral nerve sparing prostatectomy: results of a randomized, double blind, placebo-controlled pilot study
    Mauro Gacci
    Department of Urology, University of Florence, Careggi Hospital, Florence, Italy
    J Sex Med 7:234-43. 2010
    Phosphodiesterase type 5 inhibitors (PDE5-I) have acquired an established role in the treatment of post-prostatectomy erectile dysfunction (ED)...
  56. ncbi The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development
    Marco Guazzi
    Department of Medicine, Surgery and Dentistry, University of Milan, San Paolo Hospital, Milan, Italy
    Curr Med Chem 14:2181-91. 2007
    ..g., cGMP and cAMP. PDE isoenzyme 5 (PDE5) is specifically involved in cGMP inactivation in the smooth muscle cell...
  57. ncbi Phosphodiesterase type 5 inhibition coupled to strong reinforcement results in two periods of transient retention loss in the young chick
    T M Edwards
    School of Psychology, Psychiatry and Psychological Medicine, Monash University, Wellington Rd, Clayton, Victoria 3800, Australia
    Behav Brain Res 183:231-5. 2007
    Previous behavioural studies which have administered phosphodiesterase type-5 (PDE5) inhibitors have consistently demonstrated improved retention...
  58. pmc Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy contribute to adverse LV remodeling
    Sara Vandenwijngaert
    Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
    PLoS ONE 8:e58841. 2013
    ..We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure ..
  59. doi Effect of nitric oxide on the cyclic guanosine monophosphate (cGMP) pathway during meiosis resumption in bovine oocytes
    Kátia R Lancellotti Schwarz
    Departamento de Medicina Veterinaria, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de Sao Paulo, Pirassununga SP, Brazil
    Theriogenology 81:556-64. 2014
    ..Also, to our knowledge this is the first report to detect PKG1, PKG2, phosphodiesterase-5A, ADCY3, ADCY6, and ADCY9 transcripts in bovine oocytes. ..
  60. doi Pomegranate juice causes a partial improvement through lowering oxidative stress for erectile dysfunction in streptozotocin-diabetic rat
    E Onal
    Departments of Pharmacology and Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey
    Int J Impot Res 28:234-240. 2016
    ..Our results highlight the success of antioxidant mechanism of PJ in ED with diabetes and open the way for future understanding in alternative treatment combinations with PDE5 inhibitors.
  61. ncbi Novel alternative splice variants of cGMP-binding cGMP-specific phosphodiesterase
    J Kotera
    Discovery Research Laboratory, Tanabe Seiyaku Co Ltd, 2 50, Kawagishi 2 chome, Toda, Saitama, 335 8505, Japan
    J Biol Chem 273:26982-90. 1998
    ..Thus, two types of alternative splice variants of canine cGB-PDE have been identified and shown to have similar biological properties in vitro...
  62. ncbi [The endocrine basis of sexual dysfunction in the elderly]
    W Krause
    Arbeitskreis Andrologie der Deutschen Dermatologen AAD, Abteilung Andrologie, Dermatologische Klinik, Klinikum der Philipps Universität, Marburg
    Urologe A 39:411-3. 2000
    ..In an animal experiment, the intracavernous pressure, the density of alpha-receptors, and the PDE5 activity depended on normal testosterone levels...
  63. ncbi Physiological significance of nitrergic transmission in human penile erection
    P G Adaikan
    Department of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Lower Kent Ridge Road, Singapore 119 074
    Asian J Androl 2:51-6. 2000
    ..This causes relaxation of CC muscle. Phosphodiesterase type 5 (PDE5) is responsible for the degradation of cGMP and regulation of CC muscle tone...
  64. ncbi Characterization of human, dog and rabbit corpus cavernosum type 5 phosphodiesterases
    P Wang
    Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Life Sci 68:1977-87. 2001
    Human, dog and rabbit corpus cavernosum type 5 phosphodiesterases (PDE5) were isolated and their characteristics were compared. The three enzymes showed Km values of 0.8, 2.1 and 2.3 uM, respectively...
  65. ncbi Absence of clinically important HERG channel blockade by three compounds that inhibit phosphodiesterase 5--sildenafil, tadalafil, and vardenafil
    R Dustan Sarazan
    Lilly Research Laboratories, Eli Lilly and Company, 2001 W Main St, Greenfield, Indianapolis, IN 46140, USA
    Eur J Pharmacol 502:163-7. 2004
    Compounds that inhibit phosphodiesterase 5 (PDE5) have been developed for the treatment of erectile dysfunction...
  66. ncbi The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats
    G J Ahn
    Department of Efficacy and Toxicology, Preclinical Division, Research Laboratories, Dong A Pharmaceutical Company Ltd, Kyunggi, Republic of Korea
    Int J Impot Res 17:134-41. 2005
    ..87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED...
  67. ncbi Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects
    S K Kulkarni
    Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
    Methods Find Exp Clin Pharmacol 26:789-99. 2004
    ..Phosphodiesterase type 5 (PDE5) is one of the members of the superfamily that specifically cleaves cyclic guanosine monophosphate (cGMP), a key ..
  68. ncbi Clinical monograph for drug formulary review: erectile dysfunction agents
    Helen Eloise Campbell
    WellPoint Pharmacy Management, PO Box 9, Cherry Valley, NY, 13320, USA
    J Manag Care Pharm 11:151-71. 2005
    ..in recent years, most notably the introduction of sildenafil, the first oral selective phosphodiesterase type 5 (PDE5) inhibitor, in 1998...
  69. ncbi In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes
    Mario dell'Agli
    Department of Pharmacological Sciences, Faculty of Pharmacy, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
    J Agric Food Chem 53:1960-5. 2005
    ..wine-derived phenolic compounds was associated with the inhibition of phosphodiesterases (PDEs) and, in particular, PDE5. For this purpose, human recombinant PDE5A1 isoform was prepared by expression of the full-length cDNA of PDE5A1 ..
  70. ncbi Effects of combined treatment with sildenafil and itraconazole on the cardiovascular system in telemetered conscious dogs
    Eun Joo Kim
    Department of Pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea
    Drug Chem Toxicol 28:177-86. 2005
    Sildenafil, a potent PDE5 inhibitor, is widely prescribed as a treatment of erectile dysfunction. Itraconazole is an inhibitor of CYP3A4, a metabolic enzyme of sildenafil...
  71. ncbi Life after PDE4: overcoming adverse events with dual-specificity phosphodiesterase inhibitors
    Mark A Giembycz
    Department of Pharmacology and Therapeutics, Institute of Infection, Immunity and Inflammation, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
    Curr Opin Pharmacol 5:238-44. 2005
    ..The development of dual-specificity compounds that inhibit PDE4 and PDE1, PDE3, PDE5 or PDE7 could be beneficial for the treatment of chronic inflammatory lung diseases and are currently being ..
  72. ncbi [Cost of fertility and erectile dysfunction therapy: who has to pay what in the GVK?]
    I Schroeder-Printzen
    Universitätsklinikum Giessen und Marburg, Giessen
    Urologe A 44:1179-82. 2005
    ..Before 2004 medical therapy of erectile dysfunction (autoinjection therapy, PDE5 inhibitors) was included in the coverage of the general health insurance; however, it is now excluded by law...
  73. doi Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence
    Michael J Mathers
    Urological Ambulatory Remscheid, Remscheid, Germany
    BJU Int 101:1129-34. 2008
    To test the hypothesis that a variable dosage of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (25, 50, 100 mg) or vardenafil (5, 10, 25 mg) determined according to results obtained from nocturnal penile tumescence and ..
  74. doi Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy
    Francesco Montorsi
    Division of Urology, Universita Vita Salute San Raffaele, Via Olgettina 60, Milan, Italy
    Eur Urol 54:924-31. 2008
    ..data have been available from large, well-designed trials comparing on demand and nightly dosing of phosphodiesterase type 5 (PDE5) inhibitors on recovery of erectile function in postprostatectomy patients with erectile dysfunction (ED).
  75. doi Aspects of sexual satisfaction in men with erectile dysfunction: a factor analytic and logistic regression approach
    Axel Fugl-Meyer
    University of Uppsala Neuroscience, Rehabilitation Medicine, Upssala, Sweden
    J Sex Med 6:232-42. 2009
    ..Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) assess efficacy of phosphodiesterase type 5 (PDE5) inhibitor treatment of erectile dysfunction (ED).
  76. doi Combined use of PDE5 inhibitors and nitrates in the treatment of pulmonary arterial hypertension in patients with heart failure
    Josef Stehlik
    Cardiology Section, VA Salt Lake City Health Care System, Salt Lake City, UT 84148, USA
    J Card Fail 15:31-4. 2009
    Phosphodiesterase-5 (PDE5) inhibitors, which induce relaxation of smooth muscle with some selectivity for the pulmonary vasculature, are used in the treatment of pulmonary hypertension...
  77. pmc Lack of direct androgen regulation of PDE5 expression
    Rong Yang
    Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, 533 Parnassus Ave, Box 0738, San Francisco, CA 94143 0738, USA
    Biochem Biophys Res Commun 380:758-62. 2009
    ..Prostate specific antigen (PSA) promoter activity was upregulated while PDE5A promoter activity remained unchanged in DHT-treated CSMC...
  78. doi Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system
    Robert O Hughes
    Pfizer Global Research and Development, Chesterfield Parkway West, St Louis, MO 63017, USA
    Bioorg Med Chem Lett 19:4092-6. 2009
    Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described...
  79. doi Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid-beta load in an Alzheimer's disease mouse model
    Daniela Puzzo
    Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA
    J Neurosci 29:8075-86. 2009
    ..Here, we report that the phosphodiesterase 5 inhibitor (PDE5) sildenafil (Viagra), a molecule that enhances phosphorylation of CREB, a molecule involved in memory, through ..
  80. doi Acute hemodynamic effects of intravenous sildenafil citrate in congestive heart failure: comparison of phosphodiesterase type-3 and -5 inhibition
    Phil Botha
    Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
    J Heart Lung Transplant 28:676-82. 2009
    ..The phosphodiesterase 3 (PDE3) and PDE5 inhibitors both increase levels of cyclic nucleotides in the vascular smooth muscle, causing vasodilatation...
  81. ncbi [Vardenafil for refractory erectile dysfunction: the latest advances]
    Hao Yang Wang
    Department of Reproduction and Genetics, PLA Research Institute of Clinical Laboratory Medicine, Nanjing General Hospital of Nanjing Military Region, Nanjing, Jiangsu 210002, China
    Zhonghua Nan Ke Xue 15:1035-8. 2009
    In recent years, more and more attention has been drawn to the role of phosphodiesterase 5 (PDE5) in penile erection...
  82. doi Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy
    Won Ho Hahn
    Department of Pediatrics, East West Kidney Diseases Research Institute, School of Medicine, Kyung Hee University, Hoegi dong 1, Dongdaemun Gu, Seoul 130 702, Korea
    Pediatr Nephrol 25:1663-71. 2010
    ..The present study was conducted to investigate the association among 16 single nucleotide polymorphisms (SNPs) of PDE5A and childhood IgAN...
  83. doi [Treatment of pulmonary arterial hypertension]
    Xavier Jais
    Universite Paris Sud XI, Orsay, France
    Presse Med 39:1S22-32. 2010
    ..with epoprostenol and either an endothelin-receptor antagonist (ERA) or a phosphodiesterase type 5 inhibitor (PDE5 I), or both should also be discussed...
  84. doi Avanafil, a new rapid-onset phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction
    Ma Limin
    Tulane University, Health Sciences Center, Department of Urology, 1430 Tulane Avenue, SL 42, New Orleans, LA 70112, USA
    Expert Opin Investig Drugs 19:1427-37. 2010
    ..Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil and vardenafil) are currently the first-line treatment option presented to ..
  85. doi Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats
    Delphine Behr-Roussel
    Pelvipharm, Orsay, France
    Eur Urol 59:272-9. 2011
    Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate...
  86. doi GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization
    Cathy J Tralau-Stewart
    Drug Discovery Institute, Faculty of Medicine, Imperial College London, London, United Kingdom
    J Pharmacol Exp Ther 337:145-54. 2011
    ..GSK256066 was highly selective for PDE4 (>380,000-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2500-fold against PDE7), inhibited PDE4 isoforms A-D with equal affinity, and had a substantial ..
  87. ncbi [Phosphodiesterase regulation of cardiovascular functions]
    La Li
    Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China
    Sheng Li Ke Xue Jin Zhan 41:100-6. 2010
    ..The functions of blood vessels are regulated by the reactivity and phenotypes of vascular smooth muscle. PDE5 inhibitors, by enhancing the vasodilator effect of cGMP, have been successfully applied to the treatment of ..
  88. doi Treatment of erectile dysfunction and lower urinary tract symptoms by phosphodiesterase inhibitors
    Stefan Uckert
    Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, 30625 Hannover, Germany
    Handb Exp Pharmacol . 2011
    ..symptoms of lower urinary tract dysfunction is now widely accepted following the successes of phosphodiesterase 5 (PDE5) inhibitor treatment of erectile dysfunction, the treatment of urological diseases has focused on orally available ..
  89. pmc Non-invasive management of primary phosphodiesterase type 5 inhibitor failure in patients with erectile dysfunction
    Gregory Lowe
    Department of Urology, Ohio State University Medical Center, Columbus, OH, USA
    Ther Adv Urol 1:235-42. 2009
    Phosphodiesterase type 5 inhibitors (PDE5-i) have become first line therapy for the treatment of erectile dysfunction. Most initial prescriptions for PDE5-i are by primary care practitioners...
  90. ncbi [Effects and mechanisms of phosphodiesterase type 5 inhibitors on rats with overactive bladder]
    Hong de Chen
    Department of Urology, Wenzhou Medical College, Wenzhou, China
    Zhonghua Yi Xue Za Zhi 91:2001-5. 2011
    To investigate the effects and the possible mechanistic pathway of phosphodiesterase type 5 (PDE5) inhibitors on rats with overactive bladder.
  91. doi Recurrent uveitis due to sildenafil usage in a patient with Behçet's disease
    Metin Isik
    Department of Internal Medicine, Hacettepe University Hospital, Sihhiye, Ankara, Turkey
    Rheumatol Int 33:803. 2013
    ..Sildenafil (Viagra(R)) and the other phosphodiesterase type 5 (PDE5) inhibitors are the first-line options for the treatment of erectile dysfunction, but transient visual symptoms and ..
  92. doi Does current scientific and clinical evidence support the use of phosphodiesterase type 5 inhibitors for the treatment of premature ejaculation? a systematic review and meta-analysis
    Anastasios D Asimakopoulos
    UOC of Urology, Department of Surgery, University of Tor Vergata, Policlinico Casilino, Rome, Italy
    J Sex Med 9:2404-16. 2012
    ..Premature ejaculation (PE) is a highly prevalent and complex syndrome that remains poorly defined and inadequately characterized. Pharmacotherapy represents the current basis of lifelong PE treatment...
  93. doi cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function
    Mirko Jaumann
    University of Tubingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, Tubingen, Germany
    Nat Med 18:252-9. 2012
    ..mice, and its expression partly overlapped with the expression profile of cGMP-hydrolyzing phosphodiesterase 5 (Pde5)...
  94. pmc Ca2+ -activated K+ channel (KCa) stimulation improves relaxant capacity of PDE5 inhibitors in human penile arteries and recovers the reduced efficacy of PDE5 inhibition in diabetic erectile dysfunction
    R Gonzalez-Corrochano
    Servicio de Histología Investigación, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramon y Cajal, Madrid, Spain
    Br J Pharmacol 169:449-61. 2013
    ..calcium-activated potassium channels (KCa ) activation on cGMP-mediated relaxation in human penile tissues from non-diabetic and diabetic patients, and on the effects of PDE5 inhibitors on erectile responses in control and diabetic rats.
  95. doi Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice
    Subramaniam Uthayathas
    Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama Department of Pharmacology, Howard University College of Medicine, Washington, DC
    Synapse 67:741-7. 2013
    Phosphodiesterases (PDEs) belong to a family of proteins that control metabolism of cyclic nucleotides. Targeting PDE5, for enhancing cellular function, is one of the therapeutic strategies for male erectile dysfunction...
  96. doi The molecular basis for the selectivity of tadalafil toward phosphodiesterase 5 and 6: a modeling study
    Yi You Huang
    School of Pharmaceutical Sciences, Sun Yat Sen University, Guangzhou 510006, China
    J Chem Inf Model 53:3044-53. 2013
    Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction...
  97. doi In-vitro effects of PDE5 inhibitor and statin treatment on the contractile responses of experimental MetS rabbit's cavernous smooth muscle
    Yasin Erden
    Cumhuriyet University School of Medicine Department of Urology
    Arch Ital Urol Androl 86:33-8. 2014
    ....
  98. pmc Regulation of OSU-03012 toxicity by ER stress proteins and ER stress-inducing drugs
    Laurence Booth
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia
    Mol Cancer Ther 13:2384-98. 2014
    ..examined the toxic interaction between the non-coxib celecoxib derivative OSU-03012 and phosphodiesterase 5 (PDE5) inhibitors, and also determined the roles of endoplasmic reticulum stress response regulators in cell survival...
  99. doi Somatic amplifications and deletions in genome of papillary thyroid carcinomas
    Nadia Passon
    Azienda Ospedaliero Universitaria S Maria della Misericordia, Udine, Italy
    Endocrine 50:453-64. 2015
    ..Most frequent amplifications were detected at regions 2q35, 4q26, and 4q34.1, containing FN1, PDE5A, and GALNTL6 genes, respectively. Most frequent deletions occurred at regions 6q25...
  100. pmc Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity to sildenafil in female rats with type 2 diabetes
    Styliani Goulopoulou
    Department of Physiology, Georgia Regents University, Augusta, Georgia
    Am J Physiol Heart Circ Physiol 309:H297-304. 2015
    ..82 ± 0.07 vs. 10.27 ± 0.08, P < 0.05) and increased sensitivity to sildenafil [phosphodiesterase 5 (PDE5) inhibitor; pEC50: 7.89 ± 0.14 vs. 8.25 ± 0.13, P < 0.05]...
  101. pmc Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases
    Ayodeji Adegunsoye
    Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Biomed Res Int 2015:929170. 2015
    ..calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors...

Research Grants70

  1. cGMP Phosphodiesterase Inhibitors in a Mouse Model of Duchenne Muscular Dystrophy
    STANLEY FROEHNER; Fiscal Year: 2009
    ..PDE inhibitors, particularly those targeted at PDE5, reduce cardiac hypertrophy and fibrosis in a pressure induced mouse model...
  2. DAVID ALAN KASS; Fiscal Year: 2016
    ..This has led to two major NIH- sponsored multicenter trials of PDE5 inhibitors in heart failure with either reduced or preserved ejection fraction...
  3. Rick H Cote; Fiscal Year: 2016
    ..Furthermore, the increasing therapeutic reliance on PDE5 inhibitors (e.g...
  4. Structure and Regulation of the GPCR-G Protein Interactions in the Visual System
    ARNOLD EINO RUOHO; Fiscal Year: 2011
    ..spectrometry analysis;(c) The NMR solution structure of the full-length PDEg complexed with the catalytic core of a PDE5/6 chimera will be determined using 2H/13C/15N labeled proteins...
  5. A Novel HTS Cell-Based Assay For Cyclic GMP
    Gary Piazza; Fiscal Year: 2007
    ..protein composed of cyan- and yellow fluorescent proteins (CFP/YFP) fused with the cGMP binding domain of PDE2 or PDE5. Fluorescence resonance energy transfer (FRET) results from a conformational change of the protein upon cGMP ..
  6. NITRIC OXIDE AND IN VIVO BRAIN ARTERIOLAR RELAXATION
    Dale Pelligrino; Fiscal Year: 2004
    ..3 principal PDEs found in cerebral VSM-the cAMP-"preferring" PDE3, the cAMP-specific PDE4, and the cGMP-specific PDE5. Primary increases in endogenous cAMP and cGMP production will be elicited by the adenylyl and guanylyl cyclase ..
  7. REGULATION OF PDE 5 IN HUMAN PENILE SMOOTH MUSCLE CELLS
    Noel Kim; Fiscal Year: 2001
    ..function in men with impotence, resulting from a broad range of etiologies, emphasizes the crucial aspect which PDE5 plays in regulating penile smooth muscle tone...
  8. Peptide Therapy for Pulmonary Arterial Hypertension
    Jawaharlal M Patel; Fiscal Year: 2013
    ..Alternatively, pulmonary vascular cGMP levels can also be elevated via inhibition of phosphodiesterase type 5 (PDE5) to achieve a similar response...
  9. Planning a Multicenter Trial of PDE5A Inhibition for Duchenne Muscular Dystrophy
    Ronald G Victor; Fiscal Year: 2012
    ..Indeed, phosphodiesterase (PDE5A) inhibitors, which prolong the half-life of cGMP-the downstream target of NO in vascular smooth muscle-rapidly ..
  10. Nancy J Brown; Fiscal Year: 2014
    ..In contrast, three-week treatment with the phosphodiesterase 5 (PDE5) inhibitor tadalafil improves beta cell function in subjects with the metabolic syndrome without altering ..
  11. PITCH HF (CCC) Lead Application
    Marc J Semigran; Fiscal Year: 2013
    ..will be the first trial to assess the effect of a selective pulmonary vasodilator, the type 5 phosphodiesterase (PDE5) inhibitor tadalafil, on long-term clinical outcomes in heart failure (HF) patients with left ventricular (LV) ..
  12. Preeclampsia, IUGR and Hypertension: Targets for Treatment
    Joey P Granger; Fiscal Year: 2013
    ..Based on our exciting preliminary data, we propose to test the central hypothesis that PDE5 inhibitors attenuate the blood pressure and renal responses to placental ischemia in pregnant rats by inhibition of ..
  13. Kathryn N Farrow; Fiscal Year: 2016
    ..dysregulation in the pulmonary vasculature are soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5)...
  14. Regulation and function of cGMP dependent protein kinase in cardiac hypertrophy
    Eiki Takimoto; Fiscal Year: 2013
    ..We recently found that blocking cGMP degradation with phospho- diesterase5A (PDE5A) inhibitor have potent anti-hypertrophic and anti-remodeling effects...
  15. PITCH HF (DCC)
    Flora Sandra Siami; Fiscal Year: 2013
    ..will be the first trial to assess the effect of a selective pulmonary vasodilator, the type 5 phosphodiesterase (PDE5) inhibitor tadalafil, on long-term clinical outcomes in heart failure (HF) patients with left ventricular (LV) ..
  16. PDE5A Inhibition Stimulates Stem Cell Survival &Differentiation
    Muhammad Ashraf; Fiscal Year: 2013
    ..To address this, we propose the following four hypotheses. Hypothesis 1: Suppression of PDE5A using a long acting inhibitor, Tadalafil, will promote MSCs survival, engraftment and angiomyogenic ..
  17. Nitric Oxide/cGMP Modulation of Corporal Fibrosis Caused by Neuropraxia
    MONICA GABRIELA FERRINI; Fiscal Year: 2012
    ..induced by BCNR/BCNC can be prevented pharmacologically by the continuous and long-term administration of either PDE5 inhibitors, which increases intracorporeal NO and cGMP...
  18. Regulation, interaction, and inhibitor discovery of phosphodiesterases
    Hengming Ke; Fiscal Year: 2013
    ..Selective inhibitors of PDEs have been studied as therapeutic agents for various human diseases. An example is PDE5-selective inhibitor sildenafil (Viagra) that is a drug for treatment of erectile dysfunction and pulmonary ..
  19. CELLULAR BIOLOGY OF RENAL FUNCTION AND DISEASE
    Dennis Brown; Fiscal Year: 2012
    ..A novel role for AQP2 in regulating actin polymerization via interaction with RhoGAPS will be explored. Use of PDE5 inhibitors and statins to achieve VP-independent urine concentration will be tested as a potential strategy for ..
  20. Mark T Nelson; Fiscal Year: 2016
    ..corpus tissue will be addressed in Aim 2, which will also consider the role of the cGMP-specific phosphodiesterase, PDE5, and Ca2+-sensitive chloride currents (ClCa) as potential contributors to tissue-specific differences in NO ..
  21. Novel Peptide for Dynamic Regulation of Lung Endothelium NOS/cGMP Functions
    Jawaharlal M Patel; Fiscal Year: 2011
    ..Alternatively, pulmonary vascular cGMP levels can also be elevated via inhibition of phosphodiesterase type 5 (PDE5) to achieve a similar response...
  22. Role of calcium sensitization in diabetes-induced erectile dysfunction
    MICHAEL EDWARD DISANTO; Fiscal Year: 2010
    ..Although efficacious orally active PDE5 inhibitors have been developed to treat ED, a large percentage of diabetic men (with estimates as high as 50%) ..
  23. PDE5i with Tadalafil Changes the Extent of Renal Damage (PITCH_ER)
    Ravi Thadhani; Fiscal Year: 2013
    ..study provides an efficient, economical, and well-powered approach to identify potential renoprotective effects of PDE5 inhibition...
  24. Gary A Piazza; Fiscal Year: 2016
    ..NSAIDs such as sulindac sulfide (SS) are closely associated with inhibition of the cGMP-specific phosphodiesterase, PDE5. SS can selectively inhibit PDE5 to increase intracellular cGMP levels and activate protein kinase G to ..
  25. S MURTHY KARNAM; Fiscal Year: 2016
    ..are regulated via feedback phosphorylation of cyclases (AC V/VI and sGC) and phosphodiesterases (PDE3A, PDE4D5, and PDE5) by PKA and PKG...
  26. Dennis Brown; Fiscal Year: 2016
    ..Aim 2 will first expand our promising work on phosphodiesterase (PDE5) inhibitors, calcitonin and statins, which promote AQP2 membrane accumulation and increase urine concentration...
  27. MicroRNA, sulindac, and breast cancer chemoprevention
    Yaguang Xi; Fiscal Year: 2013
    ..MiR-200b can reduce the expression of the cGMP-specific phosphodiesterase PDE5, which has been previously reported to be overexpressed in tumor cells and closely associated with the apoptosis-..
  28. Lei Wang; Fiscal Year: 2015
    ..The phosphodiesterase-5 (PDE5) enzyme is highly specific for hydrolysis of cGMP...
  29. The role of myeloid suppressor cells in tumor-specific tolerance
    Ivan M Borrello; Fiscal Year: 2011
    ..We will also examine the role of PDE5 inhibitors such as sildenafil in abrogating MSC function and test various therapeutic conditions in an effort to ..
  30. BRIAN RICHARD LINDMAN; Fiscal Year: 2015
    ..Emerging preclinical and clinical data suggest that phosphodiesterase type 5 (PDE5) inhibition may help in this regard...
  31. Novel PDE5 inhibitors as a therapeutic tool against Alzheimer's Disease
    Ottavio Arancio; Fiscal Year: 2013
    ..Most importantly, sildenafil, an inhibitor of the cGMP-degrading enzyme phosphodiesterase V (PDE5), one of the components of the pathway, ameliorates synaptic and memory abnormalities in an amyloid-depositing ..
  32. Epsilon-sarcoglycan in LGMD Type 2D
    Kevin Campbell; Fiscal Year: 2009
    ..Significantly, we found that pharmacological treatment with PDE5A inhibitors relieves this form of fatigue by enhancing the nitric oxide signaling from active muscle...
  33. Basic Investigations in Brain Remodeling
    Zheng Gang Zhang; Fiscal Year: 2011
    Treatment of stroke with a selective inhibitor of phosphodiesterase type 5 (PDE5), e.g...
  34. Sonic hedgehog, a regulator of CN injury induced apoptosis
    CAROL ANN PODLASEK; Fiscal Year: 2012
    ..30-87% of prostate cancer patients treated by prostatectomy experience ED and PDE5 inhibitors are ineffective in 29-86% of prostatectomy patients who experience ED, depending on their nerve injury ..
  35. BASIS FOR RENAL RESISTANCE TO ATRIAL NATRIURETIC PEPTIDE
    Michael Humphreys; Fiscal Year: 2004
    ..We shall determine the role of heightened PDE5 activity in the renal resistance to ANP observed in rats with experimental nephrosis or liver cirrhosis by (1) ..
  36. ERECTILE DYSFUNCTION AND NITRIC OXIDE SYNTHASE IN AGING
    Nestor Gonzalez Cadavid; Fiscal Year: 2006
    ..Failure to respond to PDE5 inhibitors may be related to these factors. The overall ...
  37. PDE5 Inhibition Modulates Right Ventricular Failure
    Anna Hemnes; Fiscal Year: 2006
    ..guanylyl cyclase in response to stimulation by nitric oxide, and is cleared by phosphodiesterases, including PDE5A. Expression of PDE5A has been found in cardiomyocytes...
  38. Molecular Mechanisms of PDE5 Regulation
    Jackie Corbin; Fiscal Year: 2005
    ..The subject of this application is the cGMP-binding cGMP-specific PDE (PDE5), which is specific for cGMP over cAMP at its allosteric cGMP-binding sites and at its catalytic site...
  39. Molecular Control of cGMP Signaling by PKGs and PDEs
    Jackie Corbin; Fiscal Year: 2007
    ..cGMP effects are cGMP-dependent protein kinase (PKG), cGMP-gated ion channel proteins, cGMP-binding PDEs (PDE2, PDE5, PDE6, PDE 10, PDE11), and cAMP-dependent protein kinase (PKA) by cross-activation...
  40. COLLABORATIVE R01-CARDIAC GRAFTS-FUNCTIONAL ANALYSES
    Robert Kloner; Fiscal Year: 2003
    ....
  41. Biologic Ventricular Assist Device
    Robert Kloner; Fiscal Year: 2004
    ..Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers. ..
  42. Mesenchymal Stem Cells for Myocardial Infarction
    Robert Kloner; Fiscal Year: 2006
    ..abstract_text> ..
  43. Tadalafil Induced Modulation of Immune Response in HNSCC
    Joseph A Califano; Fiscal Year: 2010
    ..anergy in both CD4+ and CD8+ T-cells in HNSCC, and that functional elimination of MDSCs via phosphodiesterase 5 (PDE5) inhibitors can restore T cell function in lymphocytes from HNSCC patients...
  44. NITRIC OXIDE REGULATORY SYSTEM IN THE PENIS
    Arthur Burnett; Fiscal Year: 2002
    ....
  45. 2008 AUA/SBUR Summer Research Conference
    Arthur Burnett; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  46. Role of Stretch to Endothelial Pulse-Perfusion Response
    David Kass; Fiscal Year: 2005
    ..abstract_text> ..
  47. Cardiovascular Stiffening in Aged Patients with CHF
    David Kass; Fiscal Year: 2005
    ..This could lead to new therapeutic approaches to this difficult clinical problem that affects a growing aged patient population. ..
  48. EXCITATORY AMINO ACIDS IN GLAUCOMA
    Alan Laties; Fiscal Year: 2004
    ..These experiments will help test the central hypothesis--for if one can block the effects of IOP elevation with glutamate antagonists, then elevated 10P may toxic glutamate levels ganglion cell loss. ..
  49. Poly(ADP-ribose)Polymerase & Doxorubicin Cardiotoxicity
    Jon Mabley; Fiscal Year: 2002
    ..PROPOSED COMMERCIAL APPLICATIONS: The annual anticipated revenues for an effective therapeutic to prevent anti-cancer-drug induced cardiodepression is over $100 million in the US alone. ..
  50. Lower urinary tract dysfunction in Parkinson's disease
    Naoki Yoshimura; Fiscal Year: 2003
    ..This is a high priority in the urologic care of patients with Parkinson's disease. ..
  51. SIGNALING MECHANISMS IN PHARMACOLOGICAL PRECONDITIONING
    RAKESH KUKREJA; Fiscal Year: 2004
    ..These studies will help us learn a great deal on the endogenous mechanisms of delayed preconditioning and assist us in developing innovative techniques leading to one of the most effective means of salvaging ischemic myocardium. ..
  52. Bladder Pain Gene Therapy with Pro-opiomelanocortin cDNA
    Naoki Yoshimura; Fiscal Year: 2004
    ..This research project is important to provide a solid basis for potential future clinical application. ..
  53. Myicardial injury: role of poly (ADP-ribose) synthetase
    Csaba Szabo; Fiscal Year: 2005
    ..Further, based on exciting preliminary data, the final, fifth aim is focusing in establishing the role of PARS in myocardial preconditioning. ..
  54. Afferent modulation in bladde dysfunction
    Naoki Yoshimura; Fiscal Year: 2007
    ..abstract not provided ..
  55. Study of Intrinsic Bladder Activity by Optical Imaging
    Anthony Kanai; Fiscal Year: 2007
    ..To study the neural-chemical control of spontaneous detrusor activity; and III.) To determine the origin of detrusor overactivity in partially obstructed bladders. ..
  56. INFLAMMATION & CORTICOSTEROID RESPONSES IN SEVERE ASTHMA
    KIAN CHUNG; Fiscal Year: 2005
    ..The molecular mechanisms underlying loss of CR will be examined. These studies should lead to more effective therapies for chronic severe asthma. ..
  57. Molecular Anatomy of Mitochondria in HNSC
    Joseph Califano; Fiscal Year: 2006
    ..Ultimately, identified mitochondrial alterations will be used as markers for molecular detection approaches using a novel, fluorescence based gap ligase chain reaction assay. [unreadable] [unreadable]..
  58. MOLECULAR MECHANISM FOR ERECTILE FUNCTION & DYSFUNCTION
    Michael Disanto; Fiscal Year: 2002
    ..It will also provide and explanation for changes in contractility of smooth muscle cells seen in patients with erectile dysfunction. ..
  59. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  60. New Strategies to Enhance Drug Adherence in Hypertension
    Robert DeBusk; Fiscal Year: 2003
    ..Demonstration of the efficacy of nurse case management of hypertension in the proposed project may facilitate the dissemination of this approach to underserved populations throughout the U.S. ..
  61. Central betal adrenergic receptors and behavior
    Han Ting Zhang; Fiscal Year: 2004
    ..This will lead to the better understanding of pathophysiology and pharmacotherapy of depression. ..
  62. Role of DEG/ENaC in the renal myogenic response
    NIKKI JERNIGAN; Fiscal Year: 2005
    ..abstract_text> ..
  63. Sertoli Cell Mediated Engulfment of Apoptotic Germ Cells
    Kodi S Ravichandran; Fiscal Year: 2010
    ..abstract_text> ..
  64. Influences on Sexual Health
    MARGAERT NUSBAUM; Fiscal Year: 2007
    ..Nusbaum with experience crucial to her growth as an independent academic researcher in sexual health care. ..
  65. Neurophysiology and Biomechanics of Urethra in Stress Urinary Incontinence
    Naoki Yoshimura; Fiscal Year: 2008
    ..This is recognized as a high priority in the urologic/gynecologic care of SUI patients. [unreadable] [unreadable]..
  66. Genetic Investigation of Arrhythmogenic Right Ventricular Dysplasia
    Daniel Judge; Fiscal Year: 2008
    ..A more efficient type of genetic analysis will be tested. This will lead to better understanding of genetic susceptibility to sudden death from heart disease. [unreadable] [unreadable] [unreadable]..
  67. HU/JHU Head and Neck Cancer Translational Research and *
    Joseph Califano; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  68. Prostanoids and hypoxic neonatal pulmonary hypertension
    CANDICE FIKE; Fiscal Year: 2009
    ..The goal of this project is to help us understand why infants develop pulmonary hypertension, determine what happens in the lung blood vessels during disease development, and develop treatments for this disease. ..
  69. AFFERENT PLASTICITY UNDERLYING URETHRAL AND PELVIC PAIN
    Naoki Yoshimura; Fiscal Year: 2010
    ..This is recognized as a high priority in the urologic care of patients with IC/CPPS. ..
  70. Folate in Schizophrenia
    Donald C Goff; Fiscal Year: 2010
    ..This will be the first adequately-powered study to assess efficacy and identify predictors of response. ..