Gene Symbol: Pde5a
Description: phosphodiesterase 5A
Alias: PDE5A2, cGMP-specific 3',5'-cyclic phosphodiesterase, CGB-PDE, cGMP-binding cGMP specific phosphodiesterase 5A2, cGMP-binding cGMP-specific phosphodiesterase, phosphodiesterase 5A, cGMP-specific, phosphodiesterase type 5
Species: rat
Products:     Pde5a

Top Publications

  1. Murray F, MacLean M, Pyne N. Increased expression of the cGMP-inhibited cAMP-specific (PDE3) and cGMP binding cGMP-specific (PDE5) phosphodiesterases in models of pulmonary hypertension. Br J Pharmacol. 2002;137:1187-94 pubmed
    ..PHT) for 14 days increased cGMP-inhibited cAMP specific phosphodiesterase (PDE3) and cGMP binding cGMP specific phosphodiesterase (PDE5) activities in pulmonary arteries...
  2. Mo E, Amin H, Bianco I, Garthwaite J. Kinetics of a cellular nitric oxide/cGMP/phosphodiesterase-5 pathway. J Biol Chem. 2004;279:26149-58 pubmed
    ..Downstream phosphorylation in platelets was detectable within 2 s, and, with continuous exposure (1 min), this pathway could be engaged by subnanomolar NO concentrations (EC(50) = 0.5 nm). ..
  3. Perez N, Piaggio M, Ennis I, Garciarena C, Morales C, Escudero E, et al. Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. Hypertension. 2007;49:1095-103 pubmed
    ..We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction. ..
  4. Ghali Ghoul R, Tahseldar Roumieh R, Sabra R. Effect of chronic administration of sildenafil on sodium retention and on the hemodynamic complications associated with liver cirrhosis in the rat. Eur J Pharmacol. 2007;572:49-56 pubmed
    ..These results suggest that chronic sildenafil administration may help prevent or ameliorate sodium retention in cirrhosis, but that hemodynamic adverse effects may ensue. ..
  5. Takimoto E, Champion H, Li M, Belardi D, Ren S, Rodriguez E, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11:214-22 pubmed
    ..Here, we show that blocking the intrinsic catabolism of cGMP with an oral phosphodiesterase-5A (PDE5A) inhibitor (sildenafil) suppresses chamber and myocyte hypertrophy, and improves in vivo heart function in mice ..
  6. Kim D, Aizawa T, Wei H, Pi X, Rybalkin S, Berk B, et al. Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: a mechanism by which angiotensin II antagonizes cGMP signaling. J Mol Cell Cardiol. 2005;38:175-84 pubmed
    ..Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC)...
  7. Jaumann M, Dettling J, Gubelt M, Zimmermann U, Gerling A, Paquet Durand F, et al. cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function. Nat Med. 2012;18:252-9 pubmed publisher
    ..These data suggest vardenafil or related drugs as possible candidates for the treatment of NIHL. ..
  8. Buhimschi C, Garfield R, Weiner C, Buhimschi I. The presence and function of phosphodiesterase type 5 in the rat myometrium. Am J Obstet Gynecol. 2004;190:268-74 pubmed
    ..In contrast to the lung, the uterus expresses an 80-kd PDE-5 isoform. Sildenafil in pharmacologic doses inhibits mechanical uterine activity and might be of benefit if selectively used for treatment of preterm labor. ..
  9. Nagendran J, Archer S, Soliman D, Gurtu V, Moudgil R, Haromy A, et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116:238-48 pubmed
    ..The beneficial effects of phosphodiesterase type 5 (PDE5) inhibitors in pulmonary arterial hypertension are thought to result from relatively selective ..

More Information


  1. Ferrini M, Kovanecz I, Sanchez S, Vernet D, Davila H, Rajfer J, et al. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biol Reprod. 2007;76:915-23 pubmed
    ..Phosphodiesterase 5 (PDE5A) inhibitors, in part via upregulating inducible nitric oxide synthase (NOS2A), have antifibrotic properties in ..
  2. Takimoto E, Koitabashi N, Hsu S, Ketner E, Zhang M, Nagayama T, et al. Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest. 2009;119:408-20 pubmed publisher
    ..Thus, RGS2 is required for early myocardial compensation to pressure overload and mediates the initial antihypertrophic and cardioprotective effects of PDE5 inhibitors. ..
  3. Zhang Z, Klyachko V, Jackson M. Blockade of phosphodiesterase Type 5 enhances rat neurohypophysial excitability and electrically evoked oxytocin release. J Physiol. 2007;584:137-47 pubmed
    b>Phosphodiesterase type 5 (PDE5) acts specifically on cyclic guanosine monophosphate (cGMP) and terminates cGMP-mediated signalling...
  4. Bender A, Ostenson C, Giordano D, Beavo J. Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression. Cell Signal. 2004;16:365-74 pubmed
    ..We found that GM-CSF differentiation triggers a small decrease in soluble guanylyl cyclase (sGC) and a large increase in GC-A, while M-CSF significantly decreases sGC. ..
  5. Zhang M, Koitabashi N, Nagayama T, Rambaran R, Feng N, Takimoto E, et al. Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cell Signal. 2008;20:2231-6 pubmed publisher
    Cyclic GMP-selective phosphodiesterase type 5 (PDE5) has been traditionally thought to play a little role in cardiac myocytes, yet recent studies using selective inhibitors such as sildenafil suggest it can potently modulate acute and ..
  6. Vaccari S, Weeks J, Hsieh M, Menniti F, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009;81:595-604 pubmed publisher
  7. Kang K, Yu J, Yoo M, Kwon J. The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction. Int J Impot Res. 2005;17:409-16 pubmed
    This study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia...
  8. Filippi S, Morelli A, Sandner P, Fibbi B, Mancina R, Marini M, et al. Characterization and functional role of androgen-dependent PDE5 activity in the bladder. Endocrinology. 2007;148:1019-29 pubmed
    ..b>Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) decrease lower urinary tract symptoms in ..
  9. Rybalkin S, Rybalkina I, Shimizu Albergine M, Tang X, Beavo J. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO J. 2003;22:469-78 pubmed
    ..The data also suggest that development of agonists and antagonists of PDE5 activity based on binding to this site might be possible. ..
  10. Loureiro Silva M, Iwakiri Y, Abraldes J, Haq O, Groszmann R. Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. J Hepatol. 2006;44:886-93 pubmed
    ..419) and sinusoidal/post-sinusoidal (P=0.875) responses to S-nitroso-N-acetylpenicillamine. Increased PDE-5 expression is involved in the decreased vascular response to NO in cirrhotic livers. ..
  11. Choi D, Jeong J, Lim B, Chung S, Chang Y, Lee S, et al. Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. Am J Physiol Renal Physiol. 2009;297:F362-70 pubmed publisher
    ..In conclusion, this study suggests that sildenafil has antiapoptotic effects in experimental IR renal injury via ERK phosphorylation, induction of iNOS and eNOS production, and a decrease in the Bax/Bcl-2 ratio. ..
  12. Menniti F, Ren J, Coskran T, Liu J, Morton D, Sietsma D, et al. Phosphodiesterase 5A inhibitors improve functional recovery after stroke in rats: optimized dosing regimen with implications for mechanism. J Pharmacol Exp Ther. 2009;331:842-50 pubmed publisher
    Phosphodiesterase 5A (PDE5A) inhibitors improve functional recovery after middle cerebral artery occlusion (MCA-o) in rats...
  13. Ni X, Safai M, Rishi R, Baylis C, Humphreys M. Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat. J Am Soc Nephrol. 2004;15:1254-60 pubmed
    ..This may contribute to the physiologic sodium retention of normal pregnancy. ..
  14. Díaz R, Nolly M, Massarutti C, Casarini M, Garciarena C, Ennis I, et al. Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH(i): role of phosphatases. Cell Physiol Biochem. 2010;26:531-40 pubmed publisher
    This study aimed to identify the signaling pathway for the proposed link between phosphodiesterase-5A (PDE5A) inhibition and decreased cardiac Na(+)/H(+) exchanger (NHE-1) activity...
  15. Kotera J, Yanaka N, Fujishige K, Imai Y, Akatsuka H, Ishizuka T, et al. Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in Purkinje cell layers during postnatal neuronal development. Eur J Biochem. 1997;249:434-42 pubmed
    ..In addition the NO/cGMP/cGB-PDE pathway appears to be essential for the induction of long-term depression. ..
  16. Yang R, Huang Y, Lin G, Wang G, Hung S, Dai Y, et al. Lack of direct androgen regulation of PDE5 expression. Biochem Biophys Res Commun. 2009;380:758-62 pubmed publisher
    ..Prostate specific antigen (PSA) promoter activity was upregulated while PDE5A promoter activity remained unchanged in DHT-treated CSMC...
  17. Zhang W, Zang N, Jiang Y, Chen P, Wang X, Zhang X. Upregulation of Phosphodiesterase type 5 in the Hyperplastic Prostate. Sci Rep. 2015;5:17888 pubmed publisher
    ..Numerous clinical trials have demonstrated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5-Is) for treating LUTS/BPH with/without ED...
  18. Isenberg J, Ridnour L, Perruccio E, Espey M, Wink D, Roberts D. Thrombospondin-1 inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner. Proc Natl Acad Sci U S A. 2005;102:13141-6 pubmed
    ..These results demonstrate a potent antagonism between TSP1 and proangiogenic signaling downstream of NO. Further elucidation of this inhibitory signaling pathway may identify new molecular targets to regulate pathological angiogenesis. ..
  19. Das A, Xi L, Kukreja R. Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. J Biol Chem. 2008;283:29572-85 pubmed publisher
    ..Moreover, our results demonstrate that sildenafil activates a PKG-dependent novel signaling cascade that involves activation of ERK and inhibition of glycogen synthase kinase 3beta leading to cytoprotection. ..
  20. Ahn G, Kang K, Kim D, Ahn B, Kim W, Kang S, et al. DA-8159 reverses selective serotonin reuptake inhibitor-induced erectile dysfunction in rats. Urology. 2005;65:202-7 pubmed
  21. Abboud K, Bassila J, Ghali Ghoul R, Sabra R. Temporal changes in vascular reactivity in early diabetes mellitus in rats: role of changes in endothelial factors and in phosphodiesterase activity. Am J Physiol Heart Circ Physiol. 2009;297:H836-45 pubmed publisher
    ..At 4 wk, a reduction in NO activity is superimposed; at this stage, PDE activity is reduced, together with increased production of vasodilating prostaglandins, possibly as a compensatory mechanism to maintain normal vascular reactivity. ..
  22. Kostic T, Stojkov N, Janjic M, Andric S. Structural complexity of the testis and PKG I / StAR interaction regulate the Leydig cell adaptive response to repeated immobilization stress. Int J Androl. 2010;33:717-29 pubmed publisher
  23. Hahn W, Suh J, Cho B. Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy. Pediatr Nephrol. 2010;25:1663-71 pubmed publisher
    ..The present study was conducted to investigate the association among 16 single nucleotide polymorphisms (SNPs) of PDE5A and childhood IgAN...
  24. Wang T, Liu Y, Chen L, Wang X, Hu X, Feng Y, et al. Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur Respir J. 2009;33:1122-32 pubmed publisher
  25. Hu W, JIN R, Zhang J, You T, Peng Z, Ge X, et al. The critical roles of platelet activation and reduced NO bioavailability in fatal pulmonary arterial hypertension in a murine hemolysis model. Blood. 2010;116:1613-22 pubmed publisher
    ..These findings further highlight the importance of the inhibition of platelet activation and the enhancement of NO bioavailability for the treatment and prevention of hemolysis-associated (fatal) PAH. ..
  26. Nishida M, Watanabe K, Sato Y, Nakaya M, Kitajima N, Ide T, et al. Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition. J Biol Chem. 2010;285:13244-53 pubmed publisher
    ..These results suggest that phosphorylation and functional suppression of TRPC6 underlie prevention of pathological hypertrophy by PDE5 inhibition. ..
  27. Koitabashi N, Aiba T, Hesketh G, Rowell J, Zhang M, Takimoto E, et al. Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol. 2010;48:713-24 pubmed publisher
    ..Thus PDE5-inhibition blocks TRPC6 channel activation and associated Cn/NFAT activation signaling by PKG-dependent channel phosphorylation. ..
  28. Kotera J, Fujishige K, Imai Y, Kawai E, Michibata H, Akatsuka H, et al. Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases. Eur J Biochem. 1999;262:866-73 pubmed
    We have reported alternative splice variants of cGMP-binding cGMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 and PDE5A2, which possess distinct N-terminal sequences...
  29. Ahn G, Sohn Y, Kang K, Ahn B, Kwon J, Kang S, et al. The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats. Int J Impot Res. 2005;17:134-41 pubmed
    ..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. ..
  30. Witwicka H, Kobiałka M, Siednienko J, Mitkiewicz M, Gorczyca W. Expression and activity of cGMP-dependent phosphodiesterases is up-regulated by lipopolysaccharide (LPS) in rat peritoneal macrophages. Biochim Biophys Acta. 2007;1773:209-18 pubmed
    ..Moreover, the fact that most of these PDEs hydrolyze also cAMP indicates that cGMP can play a role of potent regulator of cAMP signaling in macrophages. ..
  31. Sawamura F, Kato M, Fujita K, Nakazawa T, Beardsworth A. Tadalafil, a long-acting inhibitor of PDE5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats. J Pharmacol Sci. 2009;111:235-43 pubmed
    ..Thus, it is expected that tadalafil may be an effective, once-daily treatment option in humans with PAH. ..
  32. Castro L, Verde I, Cooper D, Fischmeister R. Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes. Circulation. 2006;113:2221-8 pubmed
    ..Differential spatiotemporal distributions of cGMP may therefore contribute to the specific effects of natriuretic peptides and NO donors on cardiac function. ..
  33. Behr Roussel D, Oudot A, Compagnie S, Gorny D, Le Coz O, Bernabe J, et al. Impact of a long-term sildenafil treatment on pressor response in conscious rats with insulin resistance and hypertriglyceridemia. Am J Hypertens. 2008;21:1258-63 pubmed publisher
    ..Daily treatment with phosphodiesterase type 5 (PDE5) inhibitors has beneficial effects on endothelial function in men with increased cardiovascular ..
  34. Turgut N, Temiz T, Bagcivan I, Turgut B, Gulturk S, Karadas B. The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model. Eur J Pharmacol. 2008;589:180-7 pubmed publisher
    ..The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors. ..
  35. Heikaus C, Stout J, Sekharan M, Eakin C, Rajagopal P, Brzovic P, et al. Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: insights into nucleotide specificity, dimerization, and cGMP-dependent conformational change. J Biol Chem. 2008;283:22749-59 pubmed publisher
    ..We present the NMR solution structure of the cGMP-bound PDE5A GAF A domain...
  36. Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, et al. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med. 2006;203:2691-702 pubmed
    ..In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy. ..
  37. West C, Shaw S, Sasser J, Fekete A, Alexander T, Cunningham M, et al. Chronic vasodilation increases renal medullary PDE5A and ?-ENaC through independent renin-angiotensin-aldosterone system pathways. Am J Physiol Regul Integr Comp Physiol. 2013;305:R1133-40 pubmed publisher
    ..NIF) produced plasma volume expansion (PVE), hemodilution, and increased renal medullary phosphodiesterase 5A (PDE5A) protein. The present study examined the role of the renin-angiotensin-aldosterone system (RAAS) in this mechanism...