Open Access
Subscription Access
Open Access
Subscription Access
Physiological Activity of Phosphodiesterase
Subscribe/Renew Journal
Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the cellular levels of the second messengers, cAMP and cGMP, by controlling their rates of degradation. There are 11 different PDE families, with each family typically having several different isoforms and splice variants. These unique PDEs differ in their three-dimensional structure, kinetic properties, modes of regulation, intracellular localization, cellular expression, and inhibitor sensitivities. Current literature suggests that individual isozymes modulate distinct regulatory pathways in the cell. These properties therefore offer the opportunity for selectively targeting specific PDEs for treatment of specific disease states. The clinical and commercial success of drugs like vinpocetine, nicardipine, cilostamide, milrinone, Cilostazol, rolipram, cilomilast, roflumilast, sildenafil, tadalafil, vardenafil, zaprinast, dipyridamole, papaverine have increased interest from pharmaceutical companies and academic researchers to further explore the hidden activities of phosphodiesterase activity and development of specific inhibitors of phosphodiesterase enzymes. PDE inhibitors are currently available or in development for treatment of a variety of disease conditions like depression, neurological functioning, Alzheimer's disease, parkinsonism, schizophrenia, asthma, COPD, allergic rhinitis, psoriasis, multiple sclerosis, inflammatory disease, cardiovascular diseases, pulmonary arterial hypertension. Thus PDEs serve as better drug target and current research advancements make them essential for the field of PDE research to develop more specific inhibitors at the level of different PDE sub-families and isoforms to overcome adverse effects nausea, headache, emesis, dizziness, flushing, dyspepsia, nasal congestion or rhinitis, vasodilation which are impediment for clinical approval.
Subscription
Login to verify subscription
User
Font Size
Information
- Kopperud R. et al. cAMP effector mechanisms: Novel twists for an 'old' signaling system. FEBS Lett. 546; 2003: 121-126.
- Vaandrager AB and Jonge HR. Signalling by cGMP-dependent protein kinases. Mol. Cell Biochem. 157; 1996: 23-30.
- Henn V. et al. Compartmentalized cAMP signalling regulates vasopressin mediated water reabsorption by controlling aquaporin-2. Biochem. Soc. Trans. 33; 2005: 1316-1318.
- Boswell-Smith, V. et al. Phosphodiesterase inhibitors. Br. J. Pharmacol. 147(1); 2006: 252-257.
- Halene TB and Siegel SJ. PDE inhibitors in psychiatry-future options for dementia, depression and schizophrenia? Drug discovery today. 12(19/20); 2007: 870-878.
- Conti M and Beavo J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu. Rev. Biochem. 76; 2007: 481-511.
- Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol. Ther. 109; 2006: 366-398.
- Bender AT and Beavo JA. Cyclic nucleotide phosphodiesterase: Molecular regulation to clinical use. Pharmacological reviews. 58; 2006: 488-520.
- Dousa TP. Cyclic-3',5'-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney. Kidney Int. 55 (1); 1999: 29-62.
- Kakkar R, Raju RV and Sharma RK. Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1). Cell. Mol. Life Sci. 55(8-9); 1999: 1164-86.
- Jeon YH et al. "Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development". Cell. Mol. Life Sci. 62(11); 2005: 1198-1220.
- Esposito K, et al. Phosphodiesterase genes and antidepressant treatment response: A review. Annals of Medicine. 41; 2009: 177-185.
- Wechsler J et al. Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes. J Biol Chem. 277; 2002: 38072-38078.
- Choi YH et al. Identification of a novel isoform of the cyclic nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes. Biochem J. 353; 2001: 41-50.
- Puzzo D, et al. Role of phosphodiesterase 5 in synaptic plasticity and memory. Neuropsychiatric Disease and Treatment. 4(2); 2008: 371-387.
- Available from URL: http://www.gencompare.com/pde91.html.
- Ghosh R. et al. Phosphodiesterase inhibitors: their role and implications; International Journal of PharmTech Research. 1(4); 2009: 1148-1160.
- Rao YJ and Lei XI. Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts. Acta Pharmacol Sin. 30(1); 2009: 1-24.
- Kim KY et al. Discovery of new inhibitor for PDE3 by virtual screening. Bioorganic and Medicinal Chemistry Letters. 21; 2011: 1617-1620.
- David MG Halpin ABCD of the phosphodiesterase family: interaction and differential activity in COPD. International Journal of COPD. 3(4); 2008: 543-561.
- Nagel D J, et al. Role of nuclear Ca2+/calmodulin-stimulated phosphodiesterase 1A in vascular smooth muscle cell growth and survival. Circ Res. 98(6); 2006: 777-784.
- Jeon YH et al. Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell. Mol. Life Sci. 62 (11); 2005: 1198-220.
- Bischoff E. Potency, selectivity, and consequences of non-selectivity of PDE inhibition. Int. J. Impot. Res. 16 (1); 2004: S11-4.
- Sonnenburg WK et al. Identification of inhibitory and calmodulin-binding domains of the PDE1A1 and PDE1A2 calmodulin-stimulated cyclic nucleotide Phosphodiesterases. J. Biol. Chem., 270; 1995: 30989-31000.
- Medina AE. Therapeutic utility of phosphodiesterase type I inhibitors in neurological conditions. Frontiers in Neuroscience. 5 (21); 2011: 1-5.
- Wentzinger L et al. Cyclic nucleotide-specific phosphodiesterases of Plasmodium falciparum: PfPDEα, a nonessential cGMP-specific PDE that is an integral membrane protein. Int. J. Parasitology. 38; 2008: 1625-1637.
- Tenor H and Schudt C. Analysis of PDE isoenzyme profiles in cells and tissues by pharmacological methods, in PDE Inhibitors (Schudt C, Dent G, and Rabe K eds) London: Academic Press 2004, 21-40.
- Manganiello VC et al. Diversity in cyclic nucleotide phosphodiesterase isoenzyme families. Arch. Biochem. Biophys. 322; 1995: 1-13.
- Available from URL: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=9079
- Bo ding et al. Functional Role of Phosphodiesterase 3 in Cardiomyocyte Apoptosis: Implication in heart failure. Circulation. 111; 2005: 2469-2476.
- Aizawa T. Role of Phosphodiesterase 3 in NO/cGMP-Mediated Antiinflammatory Effects in Vascular Smooth Muscle Cells. Circulation. 93; 2003: 406-413.
- Barnes PJ. Cyclic nucleotides and phosphodiesterases and airway function. European Respiratory Journal. 8; 1995: 457-462.
- Adderley SP et al. Regulation of cAMP by phosphodiesterases in erythrocytes. Pharmacological reports. 62; 2010: 475-482.
- Klabunde RE. Cardiovascular Pharmacology Concepts. Available from: http://www.cvpharmacology.com/vasodilator/PDEI.htm
- Endoh M. Basic and Clinical Characteristics of PDE 3 Inhibitors as Cardiotonic Agents. Cardiovascular Drugs and Therapy. 21(3); 2007: 135-139.
- Meru AV et al. Intermittent claudication: An overview. Atherosclerosis. 187; 2006: 221-237.
- Katsuichi M, Juri K and Susumu K. The treatment with selective phosphodiesterase-3 inhibitor cilostazol for experimental autoimmune encephalomyelitis. Journal of Neuroimmunology. 203; 2008: 119-280.
- Sahu A. A role of phosphodiesterase-3B pathway in mediating leptin action on proopiomelanocortin and neurotensin neurons in the hypothalamus. Neurosci Lett. 479(1); 2010: 18-21.
- Available from http://www.drugsupdate.com/generic/view/315.Accessed on 10/4/2011.
- Hori M et al. NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase 3 inhibitor, suppress the asthmatic response in guinea pigs, with both bronchodilating and anti-inflammatory effects. Eur J Pharmacol. 618(1-3); 2009: 63-69.
- Swinnen JV, Joseph D and Conti R. Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes. Proc. Natl. Acad. Sci. 86; 1989: 5325-5329.
- Livi GP, et al. Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase. Mol. Cell Biol. 10; 1990: 2678-2686.
- Bolger G, et al. A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster is potential targets for antidepressant drugs. Mol Cell Biol. 13; 1993: 6558-6571.
- Millar JK, et al. Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illness. J Physiol. 584; 2007:401-405.
- Millar JK, et al. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science. 310; 2005: 1187-1191.
- Sengupta R et al. Treating brain tumors with PDE4 inhibitors. Trends in Pharmacological Sciences 3; 2011: 1-8.
- Houslay MD. The Long and Short of Vascular Smooth Muscle. Phosphodiesterase-4 As a Putative Therapeutic Target. Mol Pharmacol. 68(3); 2005: 563-567.
- Houslay MD et al. cAMP-Specific Phosphodiesterase-4 Enzymes in the Cardiovascular System A Molecular Toolbox for Generating Compartmentalized cAMP Signaling. Circ. Res. 100; 2007: 950-966.
- Hatzelmann A et al. The preclinical pharmacology of roflumilast - A selective,oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulmonary Pharmacology and Therapeutics. 23; 2010: 235-256.
- Diamant Z and, Spina D. PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease. Pulmonary Pharmacology and Therapeutics. 5; 2011: 1-8.
- Tobias B, et al. PDE inhibitors in psychiatry-future options for dementia, depression and schizophrenia?. Drug Discovery Today. 12(19/20); 2007: 870-878.
- Puzzo D et al. Role of phosphodiesterase 5 in synaptic plasticity and memory. Neuropsychiatric Disease and Treatment. 4(2); 2008: 371-387.
- Montani D et al. Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension. Nature. 26(9); 2008: 813-825.
- Cheng J. and Grande JP. PDE Inhibitors: Novel therapeutic agents for Renal disease, Exp. Biol. Med. 232; 2007: 38-51.
- Dorsey P et al. Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of erectile dysfunction. Expert Opin. Pharmacother. 11(7); 2010: 1109-1122.
- Liu L et al. Phosphodiesterase-5 Inhibitors for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis. Urology. 77 (1); 2011: 123-129.
- Samuel R, et.al. Structural characterization of sulfoaildenafil, an analog of sildenafil. J. Pharm.Biomed. Anal. 50; 2009: 228-231.
- Roumeguere T, et al. Effects of Phosphodiesterase Inhibitors on the Inflammatory Response of Endothelial Cells Stimulated by Myeloperoxidase-Modified Low-Density Lipoprotein or Tumor Necrosis Factor Alpha. European Urology. 57; 2010: 522-529.
- Barnett CF, Machado RF. Sildenafil in the treatment of pulmonary hypertension Vascular Health and Risk Management. Pharmacol. Review. 2(4); 2006: 411-422.
- Lubamba B et al. Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice. Eur Respir J 37(1); 2009: 72-78.
- Pizanis N et al. PDE-5 inhibitor donor intravenous preconditioning is superior to supplementation in standard preservation solution in experimental lung transplantation. European Journal of Cardio-thoracic Surgery. 32; 2007: 42-47.
- Luu JK et al. Acute effects of sildenafil on the electroretinogram and multifocal electroretinogram. Am J Ophthalmol. 132; 2001: 388-394.
- Giembycz MA and Smith SJ. Phosphodiesterase 7A: a new therapeutic target for alleviating chronic inflammation? Curr Pharm Des. 12(25); 2006: 3207-20.
- Goto M, et al. Inhibition of phosphodiesterase 7A ameliorates Concanavalin A-induced hepatitis in mice. International Immunopharmacology. 9; 2009: 1347-1351.
- Goto M et al. Phosphodiesterase 7A inhibitor ASB16165 suppresses proliferation and cytokine production of NKT cells. Cellular Immunology. 258; 2009: 147-151.
- Berzofsky JA and Terabe M. The contrasting roles of NKT cells in tumor immunity. Curr Mol Med. 9(6); 2009: 667-72.
- Vasan S, Tsuji M. A double-edged sword: The role of NKT cells in malaria and HIV infection and immunity. Seminars in Immunology .xxx (2009) xxx-xxx( article in press).
- Dieren JM, et al. Roles of CD1d-restricted NKT cells in the intestine. Inflamm Bowel Dis. 13(9); 2007: 1146-1152.
- Yamamoto S, et al. Amelioration of collagen-induced arthritis in mice by a novel phosphodiesterase 7 and 4 dual inhibitor, YM-393059. European Journal of Pharmacology. 559; 2007: 219-226.
- Paterniti I, et al. PDE 7 Inhibitors: New Potential Drugs for the Therapy of Spinal Cord Injury. Nature. 6(1); 2011: 1-15.
- Giembycz, MA and Smith SJ. Phosphodiesterase 7 (PDE7) as a therapeutic target. Drugs Fut. 31(3); 2006: 207
- Arnaud-Lopez L, et al.. Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function. The American Journal of Human Genetics.82; 2008: 1270-1280.
- lisatsai LC, et al. The high affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal gland. Molecular pharmacology. 79(4); 2011: 639-648.
- Dong H, et al. Phosphodiesterase 8(PDE8) regulates chemotaxis of activated lymphocytes. Biochem.biophys Res Commun. 345(2); 2006: 713-719.
- Amanda G, et al. PDE8 regulates rapid Teff cell adhesion and proliferation independent of ICER. PloS ONE 5(8); 2010: e12011.
- Andreeva SG, et al. Expression of cGMP-specific phosphodiesterase 9A mRNA in the rat brain. J. Neurosci. 21; 2001: 9068-9076.
- Wunder F. chacterisation of the first potent and selective PDE9 inhibitor using a cGMP reporter cell line. Molecular Pharmacology. 68(6); 2005: 1775-81.
- Vanderstay FJ, et al. the novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents. Neuropharmacology. 55(5); 2008: 908-18.
- Wang H et al. Insight into binding of Phosphodiesterase-9A Selective inhibitors by crystal structures and mutagenesis. J. Med. Chem. 53(4); 2010: 1726-1731.
- Hou J, et al. Structural Asymmetry of Phosphodiesterase-9, Potential Protonation of a Glutamic Acid, and Role of the Invariant Glutamine. Neuropharmacology. 6(3); 2011: 1-6.
- Ring HA. and Serra-Mestres J. Neuropsychiatry of the basal ganglia. J. Neurol. Neurosurg. Psychiatry. 72; 2002: 12-21.
- Graybiel AM. The basal ganglia. Curr. Biol. 10; 2000: R509-R511.
- Hebb AL, Robertson HA and Denovan-Wright EM. Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of neuroscience. Neuroscience. 123; 2004: 967-981.
- Seeger TF, et al. (2003) Immunohistochemical localization of PDE10A in the rat brain. Brain Res. 985; 2003: 113-126.
- Cantin LD, et al. PDE-10A inhibitors as insulin secretagogues. Bioorganic and Medicinal Chemistry Letters. 17; 2007: 2869-2873.
- Siuciak, JA et al. Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. Neuropharmacology. 51; 2006: 386-396.
- Rodefer JS, et al. PDE10A inhibition reverses subchronic PCP induced deficits in attentional set-shifting in rats. Eur. J. Neurosci. 21; 2005: 1070-1076.
- Steven M, et al. Phosphodiesterase 10A Inhibitor Activity in Preclinical Models of the Positive, Cognitive, and Negative Symptoms of Schizophrenia. J. Pharmacol. And Expt. Therapeutics. 331(2); 2009: 574-590.
- Torremans A, et al. Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats. Acta Neurobiol Exp. 70; 2010: 13-19.
- Wayman C, et al. Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology. Int J Impot Res. 17; 2005: 216-223.
- Makhlouf A, Kshirsagar A and Niederberger C. Phosphodiesterase 11: a brief review of structure, expression and function. International Journal of Impotence Research. 18; 2006: 501-509.
Abstract Views: 308
PDF Views: 2