PDE5 inhibitors as potential tools in the treatment of cystic fibrosis

Frontiers in Pharmacology

Volumn 3 SEP, Issue , 2012, Pages

  Noel, Sabrina ^a   Dhooghe, Barbara ^a   Leal, Teresinha ^a  

^a UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

Author keywords

CFTR; Cystic fibrosis; PDE5 inhibitors; Sildenafil; Taladafil; Vardenafil

Indexed keywords

CAFFEINE; CYCLIC AMP; CYCLIC GMP; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DIPYRIDAMOLE; METHYLXANTHINE; PARAXANTHINE; PF 04957325; PHOSPHODIESTERASE; PHOSPHODIESTERASE I; PHOSPHODIESTERASE III; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IX; PHOSPHODIESTERASE V; PHOSPHODIESTERASE V INHIBITOR; PHOSPHODIESTERASE VI; PHOSPHODIESTERASE VII; PHOSPHODIESTERASE VIII; PHOSPHODIESTERASE X; PHOSPHODIESTERASE XI; ROLIPRAM; SILDENAFIL; SPLEEN EXONUCLEASE; TADALAFIL; THEOPHYLLINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VARDENAFIL; VINPOCETINE;

BINDING AFFINITY; BLOOD PRESSURE; CHLORIDE TRANSPORT; CLINICAL PRACTICE; COUGHING; CYSTIC FIBROSIS; DELETION MUTANT; DRUG ABSORPTION; DRUG APPROVAL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; ENZYME SPECIFICITY; ERECTILE DYSFUNCTION; EVIDENCE BASED MEDICINE; FOOD DRUG INTERACTION; GASTROINTESTINAL SYMPTOM; HEART RATE; HUMAN; LIPID DIET; LUNG LAVAGE; NAUSEA; NEBULIZER; NONHUMAN; PNEUMONIA; PROTEIN EXPRESSION; PROTEIN FUNCTION; RESPIRATORY TRACT DISEASE; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SYSTEMIC DISEASE; WILD TYPE;

EID: 84867136562     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2012.00167     Document Type: Review

References (146)

1. Ahn, H. S., Foster, M., Cable, M., Pitts, B. J.,and Sybertz, E. J. (1991). Ca/CaMstimulated and cGMP-specific phosphodiesterases in vascular and nonvascular tissues. Adv. Exp. Med. Biol. 308, 191-197.
2. Amaral, M. D. (2004). CFTR and chaperones: processing and degradation. J. Mol. Neurosci. 23, 41-48.
3. Antoni, F. A. (2000). Molecular diversity of cyclic AMP signalling. Front. Neuroendocrinol. 21:193. doi:10.1006/frne.1999.0193
4. Aoi, M., Aihara, E., Nakashima, M., and Takeuchi, K. (2004). Participation of prostaglandin E receptor EP4 subtype in duodenal bicarbonate secretion in rats. Am. J. Phys- iol. Gastrointest. Liver Physiol. 287, G96-G103.
5. Baratti, C. M.,and Boccia, M. M. (1999). Effects of sildenafil on long-term retention of an inhibitory avoidance response in mice. Behav. Pharmacol. 10, 731-737.
6. Barnes, P. J. (2003a). Theophylline: new perspectives for an old drug. Am. J. Respir. Crit. Care Med. 167, 813-818.
7. Barnes, P. J. (2003b). Therapy of chronic obstructive pulmonary disease. Pharmacol. Ther. 97, 87-94.
8. Barnes, P. J. (2003c). Theophylline in chronic obstructive pulmonary disease: new horizons. Proc. Am. Tho- rac. Soc. 2, 334-339.
9. Barnes, P. J., and Stockley, R. A. (2005). COPD: current therapeutic interventions and future approaches. Eur. Respir. J. 25, 1084-1106.
10. Beavo, J. A., Rogers, N. L., Crofford, O. B., Hardman, J. G., Sutherland, E. W., and Newman, E. V. (1970). Effects of xanthine derivatives on lipolysis and on adenosine 3',5'-monophosphate phosphodiesterase activity. Mol. Pharmacol. 6, 597-603.
11. Bella, A. J., and Brock, G. B. (2003). Tadalafil in the treatment of erectile dysfunction. Curr. Urol. Rep. 4, 472-478.
12. Bender, A. T., and Beavo, J. A. (2006). Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol. Rev. 58, 488-520.
13. Berry, B., Altman, P., Rowe, J., and Vaisman, T. (2009). Comparison of pharmacokinetics of vardenafil administered using an ultrasonic nebulizer for inhalation versus a single 10-mg oral tablet. J. Sex. Med. PMID: 19656275. [Epub ahead of print].
14. Bhatt-Mehta, V., and Schumacher, R. E. (2003). Treatment of apnea of prematurity. Paediatr. Drugs 5, 195-210.
15. Boess, F. G., Hendrix, M., van der Staay, F. J., Erb, C., Schreiber, R., van Staveren, W., de Vente, J., Prickaerts, J., Blokland, A., and Koenig, G. (2004). Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology 47, 1081-1092.
16. Brock, G. B. (2003). Tadalafil: a new agent for erectile dysfunction. Can. J. Urol. 10(Suppl. 1), 17-22.
17. Burgess, G., Hoogkamer, H., Collings, L., and Dingemanse, J. (2008). Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur. J. Clin. Pharma- col. 64, 43-50.
18. Carev, M., Bulat, C., Karanovic, N., Lojpur, M., Jercic, A., Nenadic, D., Marovih, Z., Husedzinovic, I., and Letica, D. (2010). Combined usage of inhaled and intravenous milrinone in pulmonary hypertension after heart valve surgery. Coll. Antropol. 34, 1113-1117.
19. Carlile, G. W., Robert, R., Zhang, D., Teske, K. A., Luo, Y., Hanrahan, J. W., and Thomas, D. Y. (2007). Correctors of protein trafficking defects identified by a novel high-throughput screening assay. Chembiochem 8, 1012-1020.
20. Ceyhan, O., Birsoy, K., and Hoffman, C. S. (2012). Identification of biologically active PDE11-selective inhibitors using a yeast-based highthroughput screen. Chem. Biol. 19, 155-163.
21. Chappe, V., Mettey, Y., Vierfond, J. M., Hanrahan, J. W., Gola, M., Verrier, B., and Becq, F. (1998). Structural basis for specificity and potency of xanthine derivatives as activators of the CFTR chloride channel. Br. J. Pharmacol. 123, 683-693.
22. Cheung, W. Y. (1970). Cyclic nucleotide phosphodiesterase. Adv. Biochem. Psychopharmacol. 3, 51-65.
23. Conti, M. (2000). Phosphodiesterases and cyclic nucleotide signaling in endocrine cells. Mol. Endocrinol. 14, 1317-1327.
24. Coquil, J. F., Franks, D. J., Wells, J. N., Dupuis, M., and Hamet, P. (1980). Characteristics of a new binding protein distinct from the kinase for guanosine 3':5'-monophosphate in rat platelets. Biochim. Biophys. Acta 631, 148-165.
25. Corbin, J. D., Beasley, A., Blount, M. A., and Francis, S. H. (2005). High lung PDE5: a strong basis for treating pulmonary hypertension with PDE5 inhibitors. Biochem. Biophys. Res. Commun. 334, 930-938.
26. Curran, M., and Keating, G. (2003). Tadalafil. Drugs 63, 2203-2212; discussion 2213-2214.
27. Dalby, R., and Suman, J. (2003). Inhalation therapy: technological milestones in asthma treatment. Adv. Drug Deliv. Rev. 55, 779-791.
28. Davis, P. B. (2006). Cystic fibrosis since 1938. Am. J. Respir. Crit. Care Med. 173, 475-482.
29. Dong, H., Osmanova, V., Epstein, P. M., and Brocke, S. (2006). Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes. Biochem. Biophys. Res. Com- mun. 345, 713-719.
30. Dormer, R. L., Harris, C. M., Clark, Z., Pereira, M. M., Doull, I. J., Norez, C., Becq, F., and McPherson, M. A. (2005). Sildenafil (Viagra) corrects DeltaF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis. Thorax 60, 55-59.
31. Dov, A., Abramovitch, E., Warwar, N., and Nesher, R. (2008). Diminished phosphodiesterase-8B potentiates biphasic insulin response to glucose. Endocrinology 149, 741-748.
32. Drumm, M. L., Wilkinson, D. J., Smit, L. S., Worrell, R. T., Strong, T. V., Frizzell, R. A., Dawson, D. C., and Collins, F. S. (1991). Chloride conductance expressed by delta F508 and othermutant CFTRs inXenopus oocytes. Science 254, 1797-1799.
33. Eardley, I., and Cartledge, J. (2002). Tadalafil (Cialis) for men with erectile dysfunction. Int. J. Clin. Pract. 56, 300-304.
34. Essayan, D. M. (2001). Cyclic nucleotide phosphodiesterases. J. Allergy Clin. Immunol. 108, 671-680.
35. Estrade, M., Grondin, P., Cluzel, J., Bonhomme, B., and Doly, M. (1998). Effect of a cGMP-specific phosphodiesterase inhibitor on retinal function. Eur. J. Pharmacol. 352, 157-163.
36. Fawcett, L., Baxendale, R., Stacey, P., McGrouther, C., Harrow, I., Soderling, S., Hetman, J., Beavo, J. A., and Phillips, S. C. (2000). Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc. Natl. Acad. Sci. U.S.A. 97, 3702-3707.
37. Filgueiras, C. C., Krahe, T. E., and Medina, A. E. (2010). Phosphodiesterase type 1 inhibition improves learning in rats exposed to alcohol during the third trimester equivalent of human gestation. Neurosci. Lett. 473, 202-207.
38. Francis, S. H., and Corbin, J. D. (1988). Purification of cGMP-binding protein phosphodiesterase from rat lung. Meth. Enzymol. 159, 722-729.
39. Francis, S. H., Lincoln, T. M., and Corbin, J. D. (1980). Characterization of a novel cGMP binding protein from rat lung. J. Biol. Chem. 255, 620-626.
40. Francis, S. H., Turko, I. V., and Corbin, J. D. (2001). Cyclic nucleotide phosphodiesterases: relating structure and function. Prog. Nucleic Acid Res. Mol. Biol. 65, 1-52.
41. Fujishige, K., Kotera, J., Michibata, H., Yuasa, K., Takebayashi, S., Okumura, K., and Omori, K. (1999). Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J. Biol. Chem. 274, 18438-18445.
42. Gardner, C., Robas, N., Cawkill, D., and Fidock, M. (2000). Cloning and characterization of the human and mouse PDE7B, a novel cAMPspecific cyclic nucleotide phosphodiesterase. Biochem. Biophys. Res. Commun. 272, 186-192.
43. Gavilanes, X., Huaux, F., Meyer, M., Lebecque, P., Marbaix, E., Lison, D., Scholte, B., Wallemacq, P., and Leal, T. (2009). Azithromycin fails to reduce increased expression of neutrophil-related cytokines in primary-cultured epithelial cells from cystic fibrosis mice. J. Cyst. Fibros. 8, 203-210.
44. Ghofrani, H. A., Osterloh, I. H., and Grimminger, F. (2006). Sildenafil:from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat. Rev. Drug Discov. 5, 689-702.
45. Glavas, N. A., Ostenson, C., Schaefer, J. B., Vasta, V., and Beavo, J. A. (2001). T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3. Proc. Natl. Acad. Sci. U.S.A. 98, 6319-6324.
46. Gresser, U., and Gleiter, C. H. (2002). Erectile dysfunction: comparison of efficacy and side effects of the PDE5 inhibitors sildenafil, vardenafil and tadalafil - review of the literature. Eur. J. Med. Res. 7, 435-446.
47. Grubb, B., Lazarowski, E., Knowles, M., and Boucher, R. (1993). Isobutylmethylxanthine fails to stimulate chloride secretion in cystic fibrosis airway epithelia. Am. J. Respir. Cell Mol. Biol. 8, 454-460.
48. Guerreiro, S., Toulorge, D., Hirsch, E., Marien, M., Sokoloff, P., and Michel, P. P. (2008). Paraxanthine, the primary metabolite of caffeine, provides protection against dopaminergic cell death via stimulation of ryanodine receptor channels. Mol. Pharmacol. 74, 980-989.
49. Hamet, P., and Coquil, J. F. (1978). Cyclic GMP binding and cyclic GMP phosphodiesterase in rat platelets. J. Cyclic Nucleotide Res. 4, 281-290.
50. Haws, C. M., Nepomuceno, I. B., Krouse, M. E., Wakelee, H., Law, T., Xia, Y., Nguyen, H., and Wine, J. J. (1996). Delta F508-CFTR channels: kinetics, activation by forskolin, and potentiation by xanthines. Am. J. Physiol. 270, C1544-C1555.
51. Hayashi, M., Kita, K., Ohashi, Y., Aihara, E., and Takeuchi, K. (2007). Phosphodiesterase isozymes involved in regulation of HCO3-secretion in isolated mouse duodenum in vitro. Biochem. Pharmacol. 74, 1507-1513.
52. Hebb, A. L., Robertson, H. A., and Denovan-Wright, E. M. (2004). Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms. Neuroscience 123, 967-981.
53. Hetman, J. M., Soderling, S. H., Glavas, N. A., and Beavo, J. A. (2000a). Cloning and characterization of PDE7B, a cAMP-specific phosphodiesterase. Proc. Natl. Acad. Sci. U.S.A. 97, 472-476.
54. Hetman, J. M., Robas, N., Baxendale, R., Fidock, M., Phillips, S. C., Soderling, S. H., and Beavo, J. A. (2000b). Cloning and characterization of two splice variants of human phosphodiesterase 11A. Proc. Natl. Acad. Sci. U.S.A. 97, 12891-12895.
55. Hogan, D. L., Crombie, D. L., Isenberg, J. I., Svendsen, P., Schaffalitzky de Muckadell, O. B., and Ainsworth, M. A. (1997). CFTR mediates cAMPand Ca2+-activated duodenal epithelial HCO3-secretion. Am. J. Physiol. 272, G872-G878.
56. Jeon, K. I., Xu, X., Aizawa, T., Lim, J. H., Jono, H., Kwon, D. S., Abe, J., Berk, B. C., Li, J. D., and Yan, C. (2010). Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc. Natl. Acad. Sci. U.S.A. 107, 9795-9800.
57. Kelley, T. J., Al-Nakkash, L., Cotton, C. U., and Drumm, M. L. (1996). Activation of endogenous deltaF508 cystic fibrosis transmembrane conductance regulator by phosphodiesterase inhibition. J. Clin. Invest. 98, 513-520.
58. Kelley, T. J., Al-Nakkash, L., and Drumm, M. L. (1995). CFTRmediated chloride permeability is regulated by type III phosphodiesterases in airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 13, 657-664.
59. Kelley, T. J., Thomas, K., Milgram, L. J., and Drumm, M. L. (1997). In vivo activation of the cystic fibrosis transmembrane conductance regulator mutant deltaF508 in murine nasal epithelium. Proc. Natl. Acad. Sci. U.S.A. 94, 2604-2608.
60. Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M., and Tsui, L. C. (1989). Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080.
61. Klotz, T., Sachse, R., Heidrich, A., Jockenhovel, F., Rohde, G., Wensing, G., Horstmann, R., and Engelmann, R. (2001). Vardenafil increases penile rigidity and tumescence in erectile dysfunction patients: a RigiScan and pharmacokinetic study. World J. Urol. 19, 32-39.
62. Kobayashi, T., Gamanuma, M., Sasaki, T., Yamashita, Y., Yuasa, K., Kotera, J., and Omori, K. (2003). Molecular comparison of rat cyclic nucleotide phosphodiesterase 8 family: unique expression of PDE8B in rat brain. Gene 319, 21-31.
63. Legssyer, R., Huaux, F., Lebacq, J., Delos, M., Marbaix, E., Lebecque, P., Lison, D., Scholte, B. J., Wallemacq, P., Leal, and T. (2006). Azithromycin reduces spontaneous and induced inflammation in deltaf508 cystic fibrosis mice. Respir. Res. 7, 134.
64. Leier, G., Bangel-Ruland, N., Sobczak, K., Knieper, Y., and Weber, W. M. (2012). Sildenafil acts as potentiator and corrector of CFTR but might be not suitable for the treatment of CF lung disease. Cell Physiol. Biochem. 29, 775-790.
65. Leonard, A., Lebecque, P., Dingemanse, J., and Leal, T. (2012a). A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference. J. Cyst. Fibros. 11, 231-236.
66. Leonard, A., Lubamba, B., Dhooghe, B., Noël, S., Wallemacq, P., Lebecque, P., and Leal, T. (2012b). Comparative variability of nasal potential difference measurements in human and mice. Open J. Respir. Dis. 2, 43-56.
67. Loughney, K., Martins, T. J., Harris, E. A., Sadhu, K., Hicks, J. B., Sonnenburg, W. K., Beavo, J. A., and Ferguson, K. (1996). Isolation and characterization of cDNAs corresponding to two human calcium, calmodulinregulated, 3',5'-cyclic nucleotide phosphodiesterases. J. Biol. Chem. 271, 796-806.
68. Loughney, K., Snyder, P. B., Uher, L., Rosman, G. J., Ferguson, K., and Florio, V. A. (1999). Isolation and characterization of PDE10A, a novel human 3', 5'-cyclic nucleotide phosphodiesterase. Gene 234, 109-117.
69. Lubamba, B., Dhooghe, B., Noël, S., and Leal, T. (2012a). Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy. Clin. Biochem. PMID: 22698459. [Epub ahead of print].
70. Lubamba, B., Huaux, F., Lebacq, J., Marbaix, E., Dhooghe, B., Panin, N., Wallemacq, P., and Leal, T. (2012b). Immunomodulatory activity of vardenafil on induced lung inflammation in cystic fibrosis mice. J. Cyst. Fibros. 11, 266-273.
71. Lubamba, B., Lebacq, J., Lebecque, P., Vanbever, R., Leonard, A., Wallemacq, P., and Leal, T. (2009). Airway delivery of low dose miglustat normalizes nasal potential difference in F508del cystic fibrosis mice. Am. J. Respir. Crit. Care Med. 179, 1022-1028.
72. Lubamba, B., Lebacq, J., Reychler, G., Marbaix, E., Wallemacq, P., Lebecque, P., and Leal, T. (2011). Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice. Eur. Respir. J. 37, 72-78.
73. Lubamba, B., Lecourt, H., Lebacq, J., Lebecque, P., De Jonge, H., Wallemacq, P., and Leal, T. (2008). Preclinical evidence that sildenafil and vardenafil activate chloride transport in cystic fibrosis. Am. J. Respir. Crit. Care Med. 177, 506-515.
74. Lukacs, G. L., Mohamed, A., Kartner, N., Chang, X. B., Riordan, J. R. and Grinstein, S. (1994). Conformational maturation of CFTR but not its mutant counterpart (delta f508) occurs in the endoplasmic reticulum and requires ATP. EMBO J. 13, 6076-6086.
75. McPherson, M. A., Pereira, M. M., Lloyd Mills, C., Murray, K. J., and Dormer, R. L. (1999). A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein. FEBS Lett. 464, 48-52.
76. Medina, A. E. (2010). Vinpocetine as a potent antiinflammatory agent. Proc. Natl. Acad. Sci. U.S.A. 107, 9921-9922.
77. Medina, A. E., Krahe, T. E., and Ramoa, A. S. (2006). Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J. Neurosci. 26, 1057-1060.
78. Mehats, C., Andersen, C. B., Filopanti, M., Jin, S. L., and Conti, M. (2002). Cyclic nucleotide phosphodiesterases and their role in endocrine cell signaling. Trends Endocrinol. Metab. 13, 29-35.
79. Menniti, F. S., Faraci, W. S.,and Schmidt, C. J. (2006). Phosphodiesterases in the CNS: targets for drug development. Nat. Rev. Drug Discov. 5, 660-670.
80. Meyer, M., Huaux, F., Gavilanes, X., van den Brûle, S., Lebecque, P., Lo Re, S., Lison, D., Scholte, B., Wallemacq, P., and Leal, T. (2009). Azithromycin reduces exaggerated cytokine production by M1 alveolarmacrophages in cystic fibrosis. Am. J. Respir. Cell Mol. Biol. 41, 590-602.
81. Milligan, P. A., Marshall, S. F.,and Karlsson, M. O. (2002). A population pharmacokinetic analysis of sildenafil citrate in patients with erectile dysfunction. Br. J. Clin. Pharmacol. 53(Suppl. 1), 45S-52S.
82. Moncada, S., and Martin, J. F. (1993). Evolution of nitric oxide. Lancet 341, 1511.
83. Muirhead, G. J., Rance, D. J., Walker, D. K., and Wastall, P. (2002). Comparative human pharmacokinetics and metabolism of single-dose oral and intravenous sildenafil. Br. J. Clin. Pharmacol. 53(Suppl. 1), 13S-20S.
84. Muller, C. E.,and Jacobson, K.A. (2011). Xanthines as adenosine receptor antagonists. Handb. Exp. Pharmacol. 200, 151-199.
85. Nichols, D. J., Muirhead, G. J., and Harness, J. A. (2002). Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br. J. Clin. Pharma- col. 53(Suppl. 1), 5S-12S.
86. Nohria, A., Tsang, S. W., Fang, J. C., Lewis, E. F., Jarcho, J. A., Mudge, G. H., and Stevenson, L. W. (2003). Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J. Am. Coll. Cardiol. 41, 1797-1804.
87. O'Byrne, P. M., and Gauvreau, G. (2009). Phosphodiesterase-4 inhibition in COPD. Lancet 374, 665-667.
88. O'Grady, S. M., Jiang, X., Maniak, P. J., Birmachu, W., Scribner, L. R., Bulbulian, B., and Gullikson, G. W. (2002). Cyclic AMP-dependent Cl secretion is regulated by multiple phosphodiesterase subtypes in human colonic epithelial cells. J. Membr. Biol. 185, 137-144.
89. Ormrod, D., Easthope, S. E., and Figgitt, D. P. (2002). Vardenafil. Drugs Aging 19, 217-227.
90. Palmer, D., and Maurice, D. H. (2000). Dual expression and differential regulation of phosphodiesterase 3A and phosphodiesterase 3B in human vascular smooth muscle: implications for phosphodiesterase 3 inhibition in human cardiovascular tissues. Mol. Pharmacol. 58, 247-252.
91. Pedemonte, N., Lukacs, G. L., Du, K., Caci, E., Zegarra-Moran, O., Galietta, L. J., and Verkman, A. S. (2005). Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by highthroughput screening. J. Clin. Invest. 115, 2564-2571.
92. Perez-Torres, S., Cortes, R., Tolnay, M., Probst, A., Palacios, J. M., and Mengod, G. (2003). Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization. Exp. Neurol. 182, 322-334.
93. Pitts, W. J., Vaccaro, W., Huynh, T., Leftheris, K., Roberge, J. Y., Barbosa, J., Guo, J., Brown, B., Watson, A., Donaldson, K., Starling, G. C., Kiener, P. A., Poss, M. A., Dodd, J. H., and Barrish, J. C. (2004). Identification of purine inhibitors of phosphodiesterase 7 (PDE7). Bioorg. Med. Chem. Lett. 14, 2955-2958.
94. Podzuweit, T., Nennstiel, P., and Muller, A. (1995). Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine. Cell. Signal. 7, 733-738.
95. Porst, H., Padma-Nathan, H., Giuliano, F., Anglin, G., Varanese, L., and Rosen, R. (2003). Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology 62, 121-125; discussion 125-126.
96. Poschet, J. F., Timmins, G. S., TaylorCousar, J. L., Ornatowski, W., Fazio, J., Perkett, E., Wilson, K. R., Yu, H. D., de Jonge, H. R., and Deretic, V. (2007). Pharmacological modulation of cGMP levels by phosphodiesterase 5 inhibitors as a therapeutic strategy for treatment of respiratory pathology in cystic fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. 293, L712-719.
97. Prickaerts, J., van Staveren, W. C., Sik, A., Markerink-van Ittersum, M., Niewohner, U., van der Staay, F. J., Blokland, A., and de Vente, J. (2002). Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat. Neuroscience 113, 351-361.
98. Reed, T. M., Repaske, D. R., Snyder, G. L., Greengard, P., and Vorhees, C. V. (2002). Phosphodiesterase 1B knock-out mice exhibit exaggerated locomotor hyperactivity and DARPP-32 phosphorylation in response to dopamine agonists and display impaired spatial learning. J. Neurosci. 22, 5188-5197.
99. Repaske, D. R., Swinnen, J. V., Jin, S. L., Van Wyk, J. J., and Conti, M. (1992). A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63kDa calmodulin-dependent phosphodiesterase. J. Biol. Chem. 267, 18683-18688.
100. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L., Iannuzzi, M. C., Collins, F. S., and Tsui, L. P. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073.
101. Rivet-Bastide, M., Vandecasteele, G., Hatem, S., Verde, I., Benardeau, A., Mercadier, J. J., and Fischmeister, R. (1997). cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes. J. Clin. Invest. 99, 2710-2718.
102. Robert, R., Carlile, G. W., Pavel, C., Liu, N., Anjos, S. M., Liao, J., Luo, Y., Zhang, D., Thomas, D. Y., and Hanrahan, J. W. (2008). Structural analog of sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect. Mol. Pharmacol. 73, 478-489.
103. Rosman, G. J., Martins, T. J., Sonnenburg, W. K., Beavo, J. A., Ferguson, K., and Loughney, K. (1997). Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase. Gene 191, 89-95.
104. Rowe, S. M., Miller, S., and Sorscher, E. J. (2005). Cystic fibrosis. N. Engl. J. Med. 352, 1992-2001.
105. Rutten, K., Van Donkelaar, E. L., Ferrington, L., Blokland, A., Bollen, E., Steinbusch, H. W., Kelly, P. A., and Prickaerts, J. H. (2009). Phosphodiesterase inhibitors enhance object memory independent of cerebral blood flow and glucose utilization in rats. Neuropsychopharmacology 34, 1914-1925.
106. Sadhu, K., Hensley, K., Florio, V. A., and Wolda, S. L. (1999). Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. J. Histochem. Cytochem. 47, 895-906.
107. Sasaki, T., Kotera, J., Yuasa, K., and Omori, K. (2000). Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem. Biophys. Res. Commun. 271, 575-583.
108. Scott, A. I., Perini, A. F., Shering, P. A., and Whalley, L. J. (1991). In-patient major depression: is rolipram as effective as amitriptyline? Eur. J. Clin. Pharmacol. 40, 127-129.
109. Sebkhi, A., Strange, J. W., Phillips, S. C., Wharton, J., and Wilkins, M. R. (2003). Phosphodiesterase type 5 as a target for the treatment of hypoxiainduced pulmonary hypertension. Circulation 107, 3230-3235.
110. Sermet-Gaudelus, I., De Boeck, K., Casimir, G. J., Vermeulen, F., Leal, T., Mogenet, A., Roussel, D., Fritsch, J., Constantine, S., Reha, A., Hirawat, S., Miller, N. L., Ajayi, T., Elfring, G. L., and Miller, L. (2010). Ataluren (PTC124) induces CFTR protein expression and activity in children with nonsense mutation cystic fibrosis. Am. J. Respir. Crit. Care Med. 182, 1262-1272.
111. Shin, D. D., Brandimarte, F., De Luca, L., Sabbah, H. N., Fonarow, G. C., Filippatos, G., Komajda, M., and Gheorghiade, M. (2007). Review of current and investigational pharmacologic agents for acute heart failure syndromes. Am. J. Cardiol. 99, 4A-23A.
112. Smith, S. J., Brookes-Fazakerley, S., Donnelly, L. E., Barnes, P. J., Barnette, M. S., and Giembycz, M. A. (2003). Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells. Am. J. Physiol. 284, L279-L289.
113. Smith, S. N., Middleton, P. G., Chadwick, S., Jaffe, A., Bush, K. A., Rolleston, S., Farley, R., Delaney, S. J., Wainwright, B., Geddes, D. M., and Alton, E. W. (1999). The in vivo effects of milrinone on the airways of cystic fibrosis mice and human subjects. Am. J. Respir. Cell Mol. Biol. 20, 129-134.
114. Soderling, S. H., Bayuga, S. J., and Beavo, J. A. (1998a). Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase. Proc. Natl. Acad. Sci. U.S.A. 95, 8991-8996.
115. Soderling, S. H., Bayuga, S. J., and Beavo, J. A. (1998b). Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J. Biol. Chem. 273, 15553-15558.
116. Soderling, S. H., Bayuga, S. J.,and Beavo, J. A. (1999). Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc. Natl. Acad. Sci. U.S.A. 96, 7071-7076.
117. Soderling, S. H., and Beavo, J. A. (2000). Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr. Opin. Cell Biol. 12, 174-179.
118. Staab, A., Tillmann, C., Forgue, S. T., MacKie, A., Allerheiligen, S. R., Rapado, J., and Troconiz, I. F. (2004). Population dose-response model for tadalafil in the treatment of male erectile dysfunction. Pharm. Res. 21, 1463-1470.
119. Stark, S., Sachse, R., Liedl, T., Hensen, J., Rohde, G., Wensing, G., Horstmann, R., and Schrott, K. M. (2001). Vardenafil increases penile rigidity and tumescence in men with erectile dysfunction after a single oral dose. Eur. Urol. 40, 181-188; discussion 189-190.
120. Sullivan, M., Egerton, M., Shakur, Y., Marquardsen, A., and Houslay, M. D. (1994). Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVAh6.1). Cell. Signal. 6, 793-812.
121. Suvarna, N. U., and O'Donnell, J. M. (2002). Hydrolysis of N-methyl-daspartate receptor-stimulated cAMP and cGMP by PDE4 and PDE2 phosphodiesterases in primary neuronal cultures of rat cerebral cortex and hippocampus. J. Pharmacol. Exp. Ther. 302, 249-256.
122. Takeuchi, K., Yagi, K., Kato, S., and Ukawa, H. (1997). Roles of prostaglandin E-receptor subtypes in gastric and duodenal bicarbonate secretion in rats. Gastroenterology 113, 1553-1559.
123. Tenor, H., Hatzelmann, A., Kupferschmidt, R., Stanciu, L., Djukanovic, R., Schudt, C., Wendel, A., Church, M. K.,andShute, J.K. (1995a).Cyclic nucleotide phosphodiesterase isoenzyme activities in human alveolar macrophages. Clin. Exp. Allergy 25, 625-633.
124. Tenor, H., Hatzelmann, A., Wendel, A., and Schudt, C. (1995b). Identification of phosphodiesterase IV activity and its cyclic adenosine monophosphate-dependent up-regulation in a human keratinocyte cell line (HaCaT). J. Invest. Dermatol. 105, 70-74.
125. Tenor, H., Staniciu, L., Schudt, C., Hatzelmann, A., Wendel, A., Djukanovic, R., Church, M. K., and Shute, J. K. (1995c). Cyclic nucleotide phosphodiesterases from purified human CD4+ and CD8+ T lymphocytes. Clin. Exp. Allergy 25, 616-624.
126. Truss, M. C., Stief, C. G., Uckert, S., Becker, A. J., Wefer, J., Schultheiss, D., and Jonas, U. (2001). Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside. World J. Urol. 19, 344-350.
127. Tsai, L. C., Shimizu-Albergine, M., and Beavo, J. A. (2011). The high affinity cAMP-specific phosphodiesterase 8B (PDE8B) controls steroidogenesis in the mouse adrenal gland. Mol. Pharmacol. 79, 639-648.
128. van der Staay, F. J., Rutten, K., Bärfacker, L., Devry, J., Erb, C., Heckroth, H., Karthaus, D., Tersteegen, A., van Kampen, M., Blokland, A., Prickaerts, J., Reymann, K. G., Schröder, U. H., and Hendrix, M. (2008). The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents. Neuropharmacology 55, 908-918.
129. van Doorninck, J. H., French, P. J., Verbeek, E., Peters, R. H., Morreau, H., Bijman, J., and Scholte, B. J. (1995). A mouse model for the cystic fibrosis delta f508 mutation. EMBO J. 14, 4403-4411.
130. Van Goor, F., Straley, K. S., Cao, D., Gonzalez, J., Hadida, S., Hazlewood, A., Joubran, J., Knapp, T., Makings, L. R., Miller, M., Neuberger, T., Olson, E., Panchenko, V., Rader, J., Singh, A., Stack, J. H., Tung, R., Grootenhuis, P. D.,and Negulescu, P. (2006). Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am. J. Physiol. Lung Cell Mol. Physiol. 290, L1117-L1130.
131. Vandecasteele, G., Verde, I., RuckerMartin, C., Donzeau-Gouge, P., and Fischmeister, R. (2001). Cyclic GMP regulation of the l-type Ca(2+) channel current in human atrial myocytes. J. Physiol. (Lond.) 533, 329-340.
132. Vang, A. G., Ben-Sasson, S. Z., Dong, H., Kream, B., DeNinno, M. P., Claffey, M. M., Housley, W., Clark, R. B., Epstein, P. M., and Brocke, S. (2010). PDE8 regulates rapid Teff cell adhesion and proliferation independent of ICER. PLoS ONE 5, e12011. doi:10.1371/journal.pone.0012011
133. Vasta, V., Shimizu-Albergine, M., and Beavo, J. A. (2006). Modulation of Leydig cell function by cyclic nucleotide phosphodiesterase 8A. Proc. Natl. Acad. Sci. U.S.A. 103, 19925-19930.
134. Vergne, F., Bernardelli, P., Lorthiois, E., Pham, N., Proust, E., Oliveira, C., Mafroud, A. K., Royer, F., Wrigglesworth, R., Schellhaas, J., Barvian, M., Moreau, F., Idrissi, M., Tertre, A., Bertin, B., Coupe, M., Berna, P., and Soulard, P. (2004). Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 1: design, synthesis and structure-activity relationship studies. Bioorg. Med. Chem. Lett. 14, 4607-4613.
135. Wang, P., Wu, P., Egan, R. W., and Billah, M. M. (2001). Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution. Gene 280, 183-194.
136. Wang, T., Liu, Y., Chen, L., Wang, X., Hu, X. R., Feng, Y. L., Liu, D. S., Xu, D., Duan, Y. P., Lin, J., Ou, X. M., and Wen, F. Q. (2009). Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur. Respir. J. 33, 1122-1132.
137. Weeks, J. L. II, Zoraghi, R., Francis, S. H., and Corbin, J. D. (2007). N-Terminal domain of phosphodiesterase-11A4 (PDE11A4) decreases affinity of the catalytic site for substrates and tadalafil, and is involved in oligomerization. Biochemistry 46, 10353-10364.
138. Wells, J. N., Wu, Y. J., Baird, C. E., and Hardman, J. G. (1975). Phosphodiesterases from porcine coronary arteries: inhibition of separated forms by xanthines, papaverine, and cyclic nucleotides. Mol. Pharmacol. 11, 775-783.
139. Wharton, J., Strange, J. W., Moller, G. M., Growcott, E. J., Ren, X., Franklyn A. P., Phillips, S. C., and Wilkins, M. R. (2005). Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am. J. Respir. Crit. Care Med. 172, 105-113.
140. Xu, R. X., Rocque, W. J., Lambert, M. H., Vanderwall, D. E., Luther, M. A., and Nolte, R. T. (2004). Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J. Mol. Biol. 337, 355-365.
141. Yan, C., Zhao, A. Z., Bentley, J. K., Loughney, K., Ferguson, K., and Beavo, J. A. (1995). Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons. Proc. Natl. Acad. Sci. U.S.A. 92, 9677-9681.
142. Yang, S. W., Smotryski, J., McElroy, W. T., Tan, Z., Ho, G., Tulshian D., Greenlee, W. J., Guzzi, M., Zhang, X., Mullins, D., Xiao, L., Hruza, A., Chan, T. M., Rindgen, D., Bleickardt, C., and Hodgson, R. (2012). Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia. Bioorg. Med. Chem. Lett. 22, 235-239.
143. Yu, S. M., Hung, L. M., and Lin, C. C. (1997). cGMP-elevating agents suppress proliferation of vascular smooth muscle cells by inhibiting the activation of epidermal growth factor signaling pathway. Circulation 95, 1269-1277.
144. Zhang, H. T., Zhao, Y., Huang, Y., Dorairaj, N. R., Chandler, L. J., and O'Donnell, J. M. (2004). Inhibition of the phosphodiesterase 4 (PDE4) enzyme reverses memory deficits produced by infusion of the MEK inhibitor U0126 into the CA1 subregion of the rat hippocampus. Neuropsychopharmacology 29, 1432-1439.
145. Zhang, L., Murray, F., Zahno, A., Kanter, J. R., Chou, D., Suda, R., Fenlon, M., Rassenti, L., Cottam, H., Kipps, T. J., and Insel, P. A. (2008). Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. U.S.A. 105, 19532-19537.
146. Zhang, X., Feng, Q., and Cote, R. H. (2005). Efficacy and selectivity of phosphodiesterase-targeted drugs in inhibiting photoreceptor phosphodiesterase (PDE6) in retinal photoreceptors. Invest. Ophthalmol. Vis. Sci. 46, 3060-3066.