Genomes and Genes
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
- 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 ..
- 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. ..
- 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 pubmedb>Phosphodiesterase type 5 (PDE5) acts specifically on cyclic guanosine monophosphate (cGMP) and terminates cGMP-mediated signalling...
- 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. ..
- 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 publisherCyclic 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 ..
- 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 pubmedThis study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia...
- 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 ..
- 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. ..
- 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. ..
- 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. ..
- 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 publisherPhosphodiesterase 5A (PDE5A) inhibitors improve functional recovery after middle cerebral artery occlusion (MCA-o) in rats...
- 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. ..
- 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 publisherThis 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...
- 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. ..
- 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...
- 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...
- 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. ..
- 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. ..
- 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
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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 pubmedWe 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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 ..
- 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. ..
- 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...
- 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. ..
- 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...