Gene Symbol: PDE3A
Description: phosphodiesterase 3A
Alias: CGI-PDE, CGI-PDE A, CGI-PDE-A, HTNB, cGMP-inhibited 3',5'-cyclic phosphodiesterase A, cAMP phosphodiesterase, myocardial cGMP-inhibited, cyclic GMP-inhibited phosphodiesterase A, phosphodiesterase 3A, cGMP-inhibited
Species: human
Products:     PDE3A

Top Publications

  1. Puxeddu E, Uhart M, Li C, Ahmad F, Pacheco Rodriguez G, Manganiello V, et al. Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity. Proc Natl Acad Sci U S A. 2009;106:6158-63 pubmed publisher
    ..Specific depletion of HeLa cell PDE3A with small interfering RNA significantly decreased membrane-associated BIG1 and BIG2, which by confocal ..
  2. Pozuelo Rubio M, Campbell D, Morrice N, MacKintosh C. Phosphodiesterase 3A binds to 14-3-3 proteins in response to PMA-induced phosphorylation of Ser428. Biochem J. 2005;392:163-72 pubmed
    b>PDE3A (phosphodiesterase 3A) was identified as a phosphoprotein that co-immunoprecipitates with endogenous 14-3-3 proteins from HeLa cell extracts, and binds directly to 14-3-3 proteins in a phosphorylation-dependent manner...
  3. Meacci E, Taira M, Moos M, Smith C, Movsesian M, Degerman E, et al. Molecular cloning and expression of human myocardial cGMP-inhibited cAMP phosphodiesterase. Proc Natl Acad Sci U S A. 1992;89:3721-5 pubmed
    We have cloned a cDNA for a myocardial cGMP-inhibited cAMP phosphodiesterase (cGI PDE) from a human heart cDNA library in lambda Zap II. The open reading frame [3.5 kilobases (kb)] of cDNA clone n.13.2 (7...
  4. Li E, Xi W, Han Y, Brozovich F. Phosphodiesterase expression in the normal and failing heart. Arch Biochem Biophys. 2019;662:160-168 pubmed publisher
    ..Our results demonstrate PDE1C and PDE3A are expressed in cardiac muscle, but we could not detect the expression of PDE2A, PDE5A, PDE7A and PDE9A in ..
  5. Chen Y, Chang W, Wu L, Hsu Y, Chen C, Kuo P. Systematic Analysis of Transcriptomic Profile of Chondrocytes in Osteoarthritic Knee Using Next-Generation Sequencing and Bioinformatics. J Clin Med. 2018;7: pubmed publisher
    ..epiregulin (EREG), leucine rich repeat containing 15 (LRRC15), and phosphodiesterase 3A (PDE3A) expression patterns were similar among related OA cartilage, subchondral bone and synovial tissue arrays in ..
  6. Chen M, Yan R, Zhou K, Li X, Zhang Y, Liu C, et al. Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia. Proc Natl Acad Sci U S A. 2018;115:E10682-E10691 pubmed publisher
    ..antibody binding activates Akt, which elicits platelet apoptosis through activation of phosphodiesterase (PDE3A) and PDE3A-mediated PKA inhibition...
  7. Yasmeen S, Kaur S, Mirza A, Brodin B, Pociot F, Kruuse C. miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells. Mol Neurobiol. 2019;: pubmed publisher
    ..hCMEC/D3 cells were transfected with miRNA mimics miR-27a-3p and miR-222-3p, and the effect on PDE3A protein expression was analyzed by Western blotting. Only PDE3A is expressed in hCMEC/D3 cells...
  8. Pulkka O, Gebreyohannes Y, Wozniak A, Mpindi J, Tynninen O, Icay K, et al. Anagrelide for Gastrointestinal Stromal Tumor. Clin Cancer Res. 2019;25:1676-1687 pubmed publisher
    ..interrogated in the MediSapiens IST Online transcriptome database comprising human tissue and cancer samples, and PDE3A and PDE3B expression was studied using IHC on tissue microarrays (TMA) consisting of 630 formalin-fixed human ..
  9. Morrison R, Zheng Z, Jennings I, Thompson P, Al Rawi J. Synthesis of linear and angular aryl-morpholino-naphth-oxazines, their DNA-PK, PI3K, PDE3A and antiplatelet activity. Bioorg Med Chem Lett. 2016;26:5534-5538 pubmed publisher
    ..7 and 5.61?M). Good antiplatelet activity was noticed for the angular 7,8-fused compounds 22a, b, k and l with IC50=3.0,14.0, 2.0 and 5.0?M respectively. The antiplatelet activity is independent of PDE3. ..

More Information


  1. Renkema K, Westermann J, Nievelstein R, Lo A Njoe S, van der Zwaag B, Manshande M, et al. PDE3A gene screening improves diagnostics for patients with Bilginturan syndrome (hypertension and brachydactyly syndrome). Hypertens Res. 2018;41:981-988 pubmed publisher
    ..We report a novel PDE3A gene mutation in a mother and daughter affected with dominant brachydactyly of the hands and feet, a short stature,..
  2. Oikawa M, Wu M, Lim S, Knight W, Miller C, Cai Y, et al. Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 2013;64:11-9 pubmed publisher
    Phosphodiesterase 3A (PDE3A) is a major regulator of cAMP in cardiomyocytes...
  3. Taiyeb A, Muhsen Alanssari S, Kraemer D, Ash O, Fajt V, Ridha Albarzanchi M. Cilostazol blocks pregnancy in naturally cycling swine: An animal model. Life Sci. 2015;142:92-6 pubmed publisher
    ..CLZ is a selective inhibitor for phosphodiesterase 3A (PDE3A); an enzyme that controls oocyte maturation in many mammals including humans...
  4. Lu J, Sewer M. p54nrb/NONO regulates cyclic AMP-dependent glucocorticoid production by modulating phosphodiesterase mRNA splicing and degradation. Mol Cell Biol. 2015;35:1223-37 pubmed publisher
    ..Interestingly, the expression of multiple phosphodiesterase (PDE) isoforms, including PDE2A, PDE3A, PDE3B, PDE4A, PDE4D, and PDE11A, was induced in p54(nrb)/NONO knockdown cells...
  5. Beca S, Ahmad F, Shen W, Liu J, Makary S, Polidovitch N, et al. Phosphodiesterase type 3A regulates basal myocardial contractility through interacting with sarcoplasmic reticulum calcium ATPase type 2a signaling complexes in mouse heart. Circ Res. 2013;112:289-97 pubmed publisher
    ..The role of different PDE isozymes, particularly PDE3A vs PDE3B, in the regulation of heart function remains unclear...
  6. Vandenberghe P, Hagué P, Hockman S, Manganiello V, Demetter P, Erneux C, et al. Phosphodiesterase 3A: a new player in development of interstitial cells of Cajal and a prospective target in gastrointestinal stromal tumors (GIST). Oncotarget. 2017;8:41026-41043 pubmed publisher
    We previously identified phosphodiesterase 3A (PDE3A) as a marker for interstitial cells of Cajal (ICC) in adult mouse gut...
  7. Davari A, Abnous K, Mehri S, Ghandadi M, Hadizadeh F. Synthesis and biological evaluation of novel pyridine derivatives as potential anticancer agents and phosphodiesterase-3 inhibitors. Bioorg Chem. 2014;57:83-9 pubmed publisher
    ..All the compounds were evaluated for their PDE3A inhibitory effects, as well as their cytotoxic effects on MCF-7 and HeLa cell lines...
  8. Alam M, Lee J, Miyano T. Inhibition of PDE3A sustains meiotic arrest and gap junction of bovine growing oocytes in in vitro growth culture. Theriogenology. 2018;118:110-118 pubmed publisher
    ..IBMX; broad-spectrum PDE inhibitor), rolipram (PDE4D inhibitor), cilostamide and milrinone (PDE3A inhibitors). The mean diameters of oocytes increased similarly in all groups...
  9. Ostermeyer J, Golly F, Kaever V, Dove S, Seifert R, Schneider E. cUMP hydrolysis by PDE3B. Naunyn Schmiedebergs Arch Pharmacol. 2018;391:891-905 pubmed publisher
    ..Adipocyte differentiation of 3T3-L1 MBX cells increased mRNA of PDE3B, but not of PDE3A. Significant amounts of cUMP were detected in differentiated and undifferentiated 3T3-L1 MBX cells...
  10. Liu S, Yin H, Li C, Qin C, Cai W, Cao M, et al. Genetic effects of PDGFRB and MARCH1 identified in GWAS revealing strong associations with semen production traits in Chinese Holstein bulls. BMC Genet. 2017;18:63 pubmed publisher
    ..Among them, three SNPs were within or close to the phosphodiesterase 3A (PDE3A), membrane associated ring-CH-type finger 1 (MARCH1) and platelet derived growth factor receptor beta (PDGFRB) ..
  11. Signorello M, Leoncini G. Regulation of cAMP Intracellular Levels in Human Platelets Stimulated by 2-Arachidonoylglycerol. J Cell Biochem. 2016;117:1240-9 pubmed publisher
    ..In contrast PDEs appear to be involved. In particular PDE3A was specifically activated, as milrinone reversed cAMP reduction by 2-AG...
  12. Thys A, Vandenberghe P, Hague P, Klein O, Erneux C, Vanderwinden J. Hyperplasia of interstitial cells of cajal in sprouty homolog 4 deficient mice. PLoS ONE. 2015;10:e0124861 pubmed publisher
    ..in situ, using quantitative immunofluorescence for the receptor tyrosine kinase Kit and for phosphodiesterase 3a (PDE3A)...
  13. Taiyeb A, Muhsen Alanssari S, Dees W, Ridha Albarzanchi M, Kraemer D. Improvement in in vitro fertilization outcome following in vivo synchronization of oocyte maturation in mice. Exp Biol Med (Maywood). 2015;240:519-26 pubmed publisher
    ..Mice were superovulated and orally treated with 7.5 mg cilostazol (CLZ), a phosphodiesterase 3A (PDE3A) inhibitor, to induce ovulation of immature oocytes at different stages depending on frequency and time of ..
  14. Li H, Xie Y, Liu Y, Qi Y, Tang C, Li X, et al. Alteration in microRNA-25 expression regulate cardiac function via renin secretion. Exp Cell Res. 2018;365:119-128 pubmed publisher
    ..cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the Pde3a and Cacnalc untranslated region...
  15. Campos Chillon F, Farmerie T, Bouma G, Clay C, Carnevale E. Effects of aging on gene expression and mitochondrial DNA in the equine oocyte and follicle cells. Reprod Fertil Dev. 2015;27:925-33 pubmed publisher
    ..amphiregulin (AREG) and epiregulin (EREG) in granulosa cells, phosphodiesterase (PDE) 4D in cumulus cells and PDE3A, G-protein-coupled receptor 3 (GPR3), growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15)..
  16. Vinogradova T, Sirenko S, Lukyanenko Y, Yang D, Tarasov K, Lyashkov A, et al. Basal Spontaneous Firing of Rabbit Sinoatrial Node Cells Is Regulated by Dual Activation of PDEs (Phosphodiesterases) 3 and 4. Circ Arrhythm Electrophysiol. 2018;11:e005896 pubmed publisher
    ..b>PDE3A, PDE4B, and PDE4D were the major PDE subtypes expressed in rabbit SANC, and PDE3A was colocalized with ?-actinin, ..
  17. Moussa M, Li M, Zheng H, Yang C, Yan S, Yu N, et al. Developmental competence of buffalo (Bubalus bubalis) denuded oocytes cocultured with cumulus cells: Protective role of cumulus cells. Theriogenology. 2018;120:40-46 pubmed publisher
    ..were used to determine the relative mRNA abundance of Gdf-9, Bmp15, Zar1, Caspase-3, Bcl-2, Zp2, Zp3, Cd9 and Pde3a by Rt-qPCR and CASPASE-3 protein expression by immunofluorescence...
  18. Wobst J, Schunkert H, Kessler T. Genetic alterations in the NO-cGMP pathway and cardiovascular risk. Nitric Oxide. 2018;76:105-112 pubmed publisher
    ..e., NOS3, PDE3A, PDE5A, and MRVI1, respectively, were likewise identified as CAD risk genes...
  19. Chung Y, Lagranha C, Chen Y, Sun J, Tong G, Hockman S, et al. Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2015;112:E2253-62 pubmed publisher
    ..Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac ..
  20. Begum N, Shen W, Manganiello V. Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility. Curr Opin Pharmacol. 2011;11:725-9 pubmed publisher
    ..The exact role and contribution of the two PDE3 isoforms, PDE3A and PDE3B, in VSMC growth regulation and oocyte maturation was examined using PDE3A (3A) and PDE3B (3B) knockout (..
  21. Butt E, Nolte C, Schulz S, Beltman J, Beavo J, Jastorff B, et al. Analysis of the functional role of cGMP-dependent protein kinase in intact human platelets using a specific activator 8-para-chlorophenylthio-cGMP. Biochem Pharmacol. 1992;43:2591-600 pubmed
    ..The data also suggest that inhibition of platelet activation in intact human platelets by nitrovasodilators is mediated by cGMP-PK. ..
  22. Tripuraneni N, Azam M. Pharmacophore modeling, 3D-QSAR, and docking study of pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues as PDE4 selective inhibitors. J Mol Model. 2015;21:289 pubmed publisher
    ..Pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues in this study showed lower binding affinity toward PDE3A in comparison to PDE4...
  23. Duan L, Yu H, Li Y, Jia C. Design and discovery of 2-(4-(1H-tetrazol-5-yl)-1H-pyrazol-1-yl)-4-(4-phenyl)thiazole derivatives as cardiotonic agents via inhibition of PDE3. Bioorg Med Chem. 2015;23:6111-7 pubmed publisher
    ..derivatives, 6(a-o) were designed, synthesized and evaluated for inhibitory activity against human PDE3A and PDE3B. In PDE3 assay, entire set of targeted analogs showed considerable inhibition of PDE3A (IC50=0.24 ± 0...
  24. Guinzberg R, Díaz Cruz A, Acosta Trujillo C, Vilchis Landeros M, Vázquez Meza H, Lozano Flores C, et al. Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity. FEBS J. 2017;284:258-276 pubmed publisher
    ..cAMP which is used by two other AKAP79/150-tethered proteins: protein kinase A (PKA) and phosphodiesterase 3A (PDE3A)...
  25. Subbotina A, Ravna A, Lysaa R, Abagyan R, Bugno R, Sager G. Inhibition of PDE5A1 guanosine cyclic monophosphate (cGMP) hydrolysing activity by sildenafil analogues that inhibit cellular cGMP efflux. J Pharm Pharmacol. 2017;69:675-683 pubmed publisher
    ..screened for their ability to inhibit adenosine cyclic monophosphate (cAMP) hydrolysis by PDE1A1, PDE1B1, PDE2A1, PDE3A, PDE10A1 and PDE10A2, and cGMP hydrolysis by PDE5A, PDE6C, PDE9A2 for a low (1 nm) and high concentration (10 μ..
  26. Lu J, Nguyen L, Samadzadeh S, Masouminia M, Mendoza A, Sweeney O, et al. Expression of proteins upregulated in hepatocellular carcinoma in patients with alcoholic hepatitis (AH) compared to non-alcoholic steatohepatitis (NASH): An immunohistochemical analysis of candidate proteins. Exp Mol Pathol. 2018;104:125-129 pubmed publisher
    ..in hepatocellular carcinoma: KLF4, SCL19A1, FANCG, HRH-1, DNMT1, DNMT3B, TNFR2, DUSP4, EGFR, Integrin α6, HDACII, PDE3A, BCL-XL, and MTCO2...
  27. Ye H, Wang X, Sussman C, Hopp K, Irazabal M, Bakeberg J, et al. Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies. J Am Soc Nephrol. 2016;27:1312-20 pubmed publisher
    ..In Pkd2(-/WS25) mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein ..
  28. Wilson L, Guo M, Umana M, Maurice D. Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells. Cell Signal. 2017;36:204-211 pubmed publisher
    ..cGMP-mediated inhibition of cAMP hydrolysis by the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A)...
  29. de Waal L, Lewis T, Rees M, Tsherniak A, Wu X, Choi P, et al. Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics. Nat Chem Biol. 2016;12:102-8 pubmed publisher
    ..or DNMDP, across 766 cancer cell lines correlates with expression of the gene PDE3A, encoding phosphodiesterase 3A...
  30. Sun M, Zheng J, Xie F, Shen W, Yin S, Ma J. Cumulus Cells Block Oocyte Meiotic Resumption via Gap Junctions in Cumulus Oocyte Complexes Subjected to DNA Double-Strand Breaks. PLoS ONE. 2015;10:e0143223 pubmed publisher
    ..of adenylate cyclase 1 (Adcy1) in cumulus cells, and G-protein coupled receptor 3 (Gpr3) and phosphodiesterase 3A (Pde3a) in oocytes, and found that the mRNA expression level of Adcy1 increased significantly in DNA-damaged cumulus ..
  31. Sakai M, Suzuki T, Tomita K, Yamashita S, Palikhe S, Hattori K, et al. Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation. Am J Physiol Heart Circ Physiol. 2017;312:H1224-H1237 pubmed publisher
    ..Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium...
  32. Tian F, Zhong C, Wang X, Meng Y. PDE3A is hypermethylated in cisplatin resistant non-small cell lung cancer cells and is a modulator of chemotherapy response. Eur Rev Med Pharmacol Sci. 2017;21:2635-2641 pubmed
    In this study, we aimed to investigate the mechanism of PDE3A downregulation in chemoresistant non-small cell lung cancer (NSCLC) cells, its functional role in chemotherapy response and association with survival outcomes...
  33. Zhu X, Zhai K, Mi Y, Ji G. Expression and function of phosphodiesterases (PDEs) in the rat urinary bladder. BMC Urol. 2017;17:54 pubmed publisher
    ..PDE1B, PDE1C, PDE3A, PDE4C, PDE8A, and PDE11A were not detected...
  34. Mao Z, Li Q, Wang P, Sun Y, Liu Y. Design and Development of Novel 4-(4-(1H-Tetrazol-5-yl)-1H-pyrazol-1-yl)-6-morpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine as Cardiotonic Agent via Inhibition of PDE3. Arch Pharm (Weinheim). 2016;349:268-76 pubmed publisher
    The classical phosphodiesterase 3A (PDE3A) inhibitors provide relaxation of the vasculature system via increasing the cellular level of cyclic adenosine monophosphate (cAMP) and proved to be useful in the management of congestive heart ..
  35. Mahmood B, Damm M, Jensen T, Backe M, Dahllöf M, Poulsen S, et al. Phosphodiesterases in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia. BMC Cancer. 2016;16:938 pubmed
    ..Of note, quantification of PDE subtype immunostaining revealed a lower amount of PDE3A (p?=?0.04) and a higher amount of PDE4B (p?=?0.02) in samples from colorectal neoplasia patients...
  36. Linares Pineda T, Cañadas Garre M, Sánchez Pozo A, Calleja Hernández M. Gene polymorphisms as predictors of response to biological therapies in psoriasis patients. Pharmacol Res. 2016;113:71-80 pubmed publisher
    ..This has prompted the investigation of many genes, such as FCGR3A, HLA, IL17F, IL23R, PDE3A-SLCO1C1, TNF? and other associated genes, as potential candidates to predict response to the different biological ..
  37. Dünnes S, Voussen B, Aue A, Groneberg K, Nikolaev V, Groneberg D, et al. Phosphodiesterase 3A expression and activity in the murine vasculature is influenced by NO-sensitive guanylyl cyclase. Pflugers Arch. 2018;470:693-702 pubmed publisher
    Phosphodiesterase 3 (PDE3) exists in two isoforms (PDE3A and PDE3B) and is known to act as cGMP-inhibited cAMP-degrading PDE. Therefore, PDE3 may likely be involved in the interaction between the two second messenger pathways...
  38. Aslibekyan S, Goodarzi M, Frazier Wood A, Yan X, Irvin M, Kim E, et al. Variants identified in a GWAS meta-analysis for blood lipids are associated with the lipid response to fenofibrate. PLoS ONE. 2012;7:e48663 pubmed publisher
    ..Suggestive associations with fenofibrate response were observed for markers in or near PDE3A, MOSC1, FLJ36070, CETP, the APOE-APOC1-APOC4-APOC2, and CILP2...
  39. Quaynor S, Bosley M, Duckworth C, Porter K, Kim S, Kim H, et al. Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome. Mol Cell Endocrinol. 2016;437:86-96 pubmed publisher
    ..candidate genes including: AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2, PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic variants were found in 8/48 (16.7%) and 1/48 (2...
  40. Sumbria R, Vasilevko V, Grigoryan M, Paganini Hill A, Kim R, Cribbs D, et al. Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages. J Neuroinflammation. 2017;14:114 pubmed publisher
    ..Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects...
  41. Lubelwana Hafver T, Wanichawan P, Manfra O, de Souza G, Lunde M, Martinsen M, et al. Mapping the in vitro interactome of cardiac sodium (Na+ )-calcium (Ca2+ ) exchanger 1 (NCX1). Proteomics. 2017;17: pubmed publisher
    ..Ten novel protein partners (DYRK1A, PPP2R2A, SNTB1, DMD, RABGGTA, DNAJB4, BAG3, PDE3A, POPDC2, STK39) were validated for binding to NCX1, and two partners (DYRK1A, SNTB1) increased NCX1 activity when ..
  42. Manns J, Brenna K, Colman R, Sheth S. Differential regulation of human platelet responses by cGMP inhibited and stimulated cAMP phosphodiesterases. Thromb Haemost. 2002;87:873-9 pubmed
    ..contain two cAMP phosphodiesterases (PDEs) which regulate intracellular cAMP levels, cGMP-inhibited cAMP PDE (PDE3A) and cGMP-stimulated PDE (PDE2A)...
  43. Wu H, Lee J, Vincent L, Wang Q, Gu M, Lan F, et al. Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromised β-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy. Cell Stem Cell. 2015;17:89-100 pubmed publisher
    ..components were unaltered between control and DCM iPSC-CMs, we found that phosphodiesterases (PDEs) 2A and PDE3A were upregulated in DCM iPSC-CMs and that PDE2A was also upregulated in DCM patient tissue...
  44. Ahmad F, Shen W, Vandeput F, Szabo Fresnais N, Krall J, Degerman E, et al. Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. J Biol Chem. 2015;290:6763-76 pubmed publisher
    ..Studies in mice showed that PDE3A, not PDE3B, is the subfamily responsible for these inotropic effects and that murine PDE3A1 associates with ..
  45. Marroni F, Pfeufer A, Aulchenko Y, Franklin C, Isaacs A, Pichler I, et al. A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project. Circ Cardiovasc Genet. 2009;2:322-8 pubmed publisher
    ..Our results suggested an association between the RR interval and GPR133 and confirmed an association between the QT interval and NOS1AP. ..
  46. Hunter R, MacKintosh C, Hers I. Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets. J Biol Chem. 2009;284:12339-48 pubmed publisher
    ..we demonstrate that a variety of platelet agonists, including thrombin, significantly enhance the activity of PDE3A in a phosphorylation-dependent manner...
  47. Adderley S, DuFaux E, Sridharan M, Bowles E, Hanson M, Stephenson A, et al. Iloprost- and isoproterenol-induced increases in cAMP are regulated by different phosphodiesterases in erythrocytes of both rabbits and humans. Am J Physiol Heart Circ Physiol. 2009;296:H1617-24 pubmed publisher
    ..These studies demonstrate that PDE activity in these cells is localized to specific signaling pathways. ..
  48. Simino J, Sung Y, Kume R, Schwander K, Rao D. Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9. Front Genet. 2013;4:277 pubmed publisher
    ..one low-frequency variant, and SNPs near/in genes ESRRG, FAM179A, CRIPT-SOCS5, KAT2B, ADCY2, GLI3, ZNF716, SLIT1, PDE3A, KERA-LUM, RNF219-AS1, CLEC3A, FBXO15, and IGSF5...
  49. Saifuzzaman M, Morrison R, Zheng Z, Orive S, Hamilton J, Thompson P, et al. Synthesis and biological evaluation of 8-aryl-2-morpholino-7-O-substituted benzo[e][1,3]oxazin-4-ones against DNA-PK, PI3K, PDE3A enzymes and platelet aggregation. Bioorg Med Chem. 2017;25:5531-5536 pubmed publisher
    ..A piperazinyl derivative 26a effectively inhibited ADP-induced platelet aggregation with an IC50 of 8?M. ..
  50. Muñoz Gutiérrez C, Cáceres Rojas D, Adasme Carreño F, Palomo I, Fuentes E, Caballero J. Docking and quantitative structure-activity relationship of bi-cyclic heteroaromatic pyridazinone and pyrazolone derivatives as phosphodiesterase 3A (PDE3A) inhibitors. PLoS ONE. 2017;12:e0189213 pubmed publisher
    PDE3s belong to the phosphodiesterases family, where the PDE3A isoform is the major subtype in platelets involved in the cAMP regulation pathway of platelet aggregation...
  51. Kasuya J, Liang S, Goko H, Park S, Kato K, Xu Z, et al. Cardiac type cGMP-inhibited phosphodiesterase (PDE3A) gene structure: similarity and difference to adipocyte type PDE3B gene. Biochem Biophys Res Commun. 2000;268:827-34 pubmed
    Phosphodiesterase type 3 isoforms, PDE3A and 3B, are expressed primarily in cardiovascular and adipose tissues, respectively. We previously reported a shorter transcript of 4...
  52. Tang K, Jang E, Haslam R. Expression and mutagenesis of the catalytic domain of cGMP-inhibited phosphodiesterase (PDE3) cloned from human platelets. Biochem J. 1997;323 ( Pt 1):217-24 pubmed
    ..of this clone established that both the platelet and the cardiac forms of PDE3 were derived from the same gene (PDE3A)...
  53. Han S, Vaccari S, Nedachi T, Andersen C, Kovacina K, Roth R, et al. Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation. EMBO J. 2006;25:5716-25 pubmed
    cGMP-inhibited cAMP phosphodiesterase 3A (PDE3A) is expressed in mouse oocytes, and its function is indispensable for meiotic maturation as demonstrated by genetic ablation...
  54. Yan C, Miller C, Abe J. Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart. Circ Res. 2007;100:489-501 pubmed
    ..b>PDE3A expression is downregulated in human and animal failing hearts...
  55. Julià A, Ferrándiz C, Dauden E, Fonseca E, Fernández López E, Sanchez Carazo J, et al. Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis. Pharmacogenomics J. 2015;15:322-5 pubmed publisher
    ..However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly ..
  56. Acosta Colman I, Palau N, Tornero J, Fernandez Nebro A, Blanco F, Gonzalez Alvaro I, et al. GWAS replication study confirms the association of PDE3A-SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics. 2013;14:727-34 pubmed publisher
    ..SNPs from NR2FR2, MAP2K6, CBLN2 and PDE3A-SLCO1C1 candidate loci were genotyped...
  57. Dastani Z, Hivert M, Timpson N, Perry J, Yuan X, Scott R, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8:e1002607 pubmed publisher
    ..4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. ..
  58. Surapisitchat J, Jeon K, Yan C, Beavo J. Differential regulation of endothelial cell permeability by cGMP via phosphodiesterases 2 and 3. Circ Res. 2007;101:811-8 pubmed
    ..permeability is dependent on the concentration of cGMP present and on the relative expression levels of PDE2A and PDE3A. When cAMP synthesis was slightly elevated with a submaximal concentration of 7-deacetyl-7-(O-[N-methylpiperazino]-..
  59. Wechsler J, Choi Y, Krall J, Ahmad F, Manganiello V, Movsesian M. Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes. J Biol Chem. 2002;277:38072-8 pubmed
    b>PDE3A cyclic nucleotide phosphodiesterases regulate cAMP- and cGMP-mediated intracellular signaling in cardiac myocytes. We used antibodies to different regions of PDE3A to demonstrate the presence of three PDE3A isoforms in these cells...
  60. Kuthe A, Eckel H, Stief C, Uckert S, Forssmann W, Jonas U, et al. Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum. Chem Biol Interact. 1999;119-120:593-8 pubmed
    ..Thus, we investigated the PDE3A isoform from penile cavernous tissues of male patients with and without symptoms of erectile dysfunction at the ..
  61. Nogueira D, Albano C, Adriaenssens T, Cortvrindt R, Bourgain C, Devroey P, et al. Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro. Biol Reprod. 2003;69:1042-52 pubmed
    ..Ultrastructure analysis of COC derived from follicles between 8 and 12 mm showed that the induced extension of prophase I arrest in vitro resulted in cytoplasm changes but not in apparent nuclear changes during culture. ..
  62. Penmatsa H, Zhang W, Yarlagadda S, Li C, Conoley V, Yue J, et al. Compartmentalized cyclic adenosine 3',5'-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains. Mol Biol Cell. 2010;21:1097-110 pubmed publisher
    ..In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel...
  63. Choi Y, Ekholm D, Krall J, Ahmad F, Degerman E, Manganiello V, et al. Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes. Biochem J. 2001;353:41-50 pubmed
    We have identified a new cyclic-nucleotide phosphodiesterase isoform, PDE3A, and cloned its cDNA from cultured aortic myocytes...
  64. Vasan R, Glazer N, Felix J, Lieb W, Wild P, Felix S, et al. Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. JAMA. 2009;302:168-78 pubmed publisher
    ..Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease. ..
  65. Maass P, Aydin A, Luft F, Schächterle C, Weise A, Stricker S, et al. PDE3A mutations cause autosomal dominant hypertension with brachydactyly. Nat Genet. 2015;47:647-53 pubmed publisher
    ..Here we report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (..
  66. Xiong X, Lan D, Li J, Lin Y, Li M. Supplementation of cilostazol during in vitro maturation enhances the meiosis and developmental competence of yak oocytes by influencing cAMP content and mRNA expression. Anim Reprod Sci. 2017;186:21-30 pubmed publisher
    ..cyclase 3 (ADCY3) and protein kinase 1 (PKA1), as well as decreased the abundance of phosphodiesterase 3A (PDE3A) in COCs and IVF blastocysts, compared with their control counterparts (P<0.05)...
  67. Nazir M, Senkowski W, Nyberg F, Blom K, Edqvist P, Jarvius M, et al. Targeting tumor cells based on Phosphodiesterase 3A expression. Exp Cell Res. 2017;361:308-315 pubmed publisher
    We and others have previously reported a correlation between high phosphodiesterase 3A (PDE3A) expression and selective sensitivity to phosphodiesterase (PDE) inhibitors...
  68. Degerman E, Moos M, Rascon A, Vasta V, Meacci E, Smith C, et al. Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase. Biochim Biophys Acta. 1994;1205:189-98 pubmed
    ..The smaller fragments (62 and 55/53 kDa) contain the catalytic domain; the larger fragments (110 and 79 kDa) also contain the regulatory domain with phosphorylation sites for A-kinase. ..
  69. Wang W, Yin R, Wu D, Aung L, Huang P, Zeng X, et al. Phosphodiesterase 3A rs7134375 single nucleotide polymorphism and serum lipid levels. Mol Med Rep. 2014;9:1618-28 pubmed publisher
    The association between the phosphodiesterase 3A (PDE3A) rs7134375 single nucleotide polymorphism (SNP) and serum lipid levels are not well understood in the general population...
  70. Zhang W, Colman R. Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A. Blood. 2007;110:1475-82 pubmed
    ..When washed human platelets were stimulated with thrombin, cAMP-dependent phosphodiesterase (PDE3A) activity was significantly increased...
  71. Aston K, Carrell D. Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl. 2009;30:711-25 pubmed publisher
  72. Hambleton R, Krall J, Tikishvili E, Honeggar M, Ahmad F, Manganiello V, et al. Isoforms of cyclic nucleotide phosphodiesterase PDE3 and their contribution to cAMP hydrolytic activity in subcellular fractions of human myocardium. J Biol Chem. 2005;280:39168-74 pubmed
    ..We examined the effects of cGMP on cAMP hydrolysis in these fractions. PDE3A-136, PDE3A-118, and PDE3A-94 have similar K(m) and k(cat) values for cAMP and are equal in their sensitivities to ..
  73. Boda H, Uchida H, Takaiso N, Ouchi Y, Fujita N, Kuno A, et al. A PDE3A mutation in familial hypertension and brachydactyly syndrome. J Hum Genet. 2016;61:701-3 pubmed publisher
    ..Mutations in the PDE3A gene located at 12p12.2-p11.2 were recently identified in HTNB families...
  74. Berrisch S, Ostermeyer J, Kaever V, Kälble S, Hilfiker Kleiner D, Seifert R, et al. cUMP hydrolysis by PDE3A. Naunyn Schmiedebergs Arch Pharmacol. 2017;390:269-280 pubmed publisher
    As previously reported, the cardiac phosphodiesterase PDE3A hydrolyzes cUMP. Moreover, cUMP-degrading activity was detected in cow and dog hearts several decades ago...
  75. Feijge M, Ansink K, Vanschoonbeek K, Heemskerk J. Control of platelet activation by cyclic AMP turnover and cyclic nucleotide phosphodiesterase type-3. Biochem Pharmacol. 2004;67:1559-67 pubmed
    ..This crucial role of PDE3, but not of PDE5, extends to all major processes in thrombus formation: assembly of platelets into aggregates, secretion of autocrine products, and procoagulant activity. ..
  76. Ghigo A, Perino A, Mehel H, Zahradnikova A, Morello F, Leroy J, et al. Phosphoinositide 3-kinase ? protects against catecholamine-induced ventricular arrhythmia through protein kinase A-mediated regulation of distinct phosphodiesterases. Circulation. 2012;126:2073-83 pubmed publisher
    ..PI3K? coordinates the coincident signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that prevents calcium-dependent ventricular arrhythmia. ..
  77. Krintel S, Palermo G, Johansen J, Germer S, Essioux L, Benayed R, et al. Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNF? inhibitors in patients with rheumatoid arthritis. Pharmacogenet Genomics. 2012;22:577-89 pubmed publisher
    ..A GSEA suggested that the transforming growth factor ?, TNF, mitogen-activated protein kinase, and mammalian target of rapamycin pathways may be associated with treatment response. ..
  78. 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
    ..2. PDE3A/B gene transcript levels were increased in the main, first, intrapulmonary and resistance pulmonary arteries by ..
  79. Ahluwalia M, Donovan H, Singh N, Butcher L, Erusalimsky J. Anagrelide represses GATA-1 and FOG-1 expression without interfering with thrombopoietin receptor signal transduction. J Thromb Haemost. 2010;8:2252-61 pubmed publisher
  80. Cheung P, Xu H, McLaughlin M, Ghazaleh F, Livi G, Colman R. Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis. Blood. 1996;88:1321-9 pubmed
    ..The major PDE activity in platelets is PDE3A (cyclic guanosine monophosphate [cGMP]-inhibited PDE)...
  81. Smith S, Plant D, Lee X, Massey J, Hyrich K, Morgan A, et al. Previously reported PDE3A-SLCO1C1 genetic variant does not correlate with anti-TNF response in a large UK rheumatoid arthritis cohort. Pharmacogenomics. 2016;17:715-20 pubmed publisher
    ..The genetic variant, rs3794271, located within the PDE3A-SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria ..
  82. Rhee D, Hockman S, Choi S, Kim Y, Park C, Manganiello V, et al. SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A. Biosci Rep. 2017;: pubmed publisher
    Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation...
  83. Corradini E, Klaasse G, Leurs U, Heck A, Martin N, Scholten A. Charting the interactome of PDE3A in human cells using an IBMX based chemical proteomics approach. Mol Biosyst. 2015;11:2786-97 pubmed publisher
    ..more selective PDE inhibitors, cilostamide and papaverine, allowed us to selectively probe the interactome of PDE3A in HeLa cells...
  84. Hung S, Zhang W, Pixley R, Jameson B, Huang Y, Colman R, et al. New insights from the structure-function analysis of the catalytic region of human platelet phosphodiesterase 3A: a role for the unique 44-amino acid insert. J Biol Chem. 2006;281:29236-44 pubmed
    Human phosphodiesterase 3A (PDE3A) degrades cAMP, the major inhibitor of platelet function, thus potentiating platelet function. Of the 11 human PDEs, only PDE3A and 3B have 44-amino acid inserts in the catalytic domain...
  85. Löbbert R, Winterpacht A, Seipel B, Zabel B. Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p 15.1. Genomics. 1996;37:211-8 pubmed
    ..88% homology and higher correspondence in functional domains to the rat cGMP inhibited phosphodiesterase gene (PDE3A). In concordance with the expression data of the rat PDE3A gene, a 5...
  86. Loughney K, Martins T, Harris E, Sadhu K, Hicks J, Sonnenburg W, et al. Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases. J Biol Chem. 1996;271:796-806 pubmed
    ..Both PDE1C enzymes were inhibited by isobutylmethylxanthine, 8-methoxymethyl isobutylmethylxanthine, zaprinast, and vinpocetine. ..
  87. Wheeler H, Gamazon E, Stark A, O Donnell P, Gorsic L, Huang R, et al. Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations. Pharmacogenomics J. 2013;13:35-43 pubmed publisher
    ..Seven genes previously implicated in platinating agent response, including BCL2 (B-cell CLL/lymphoma 2), GSTM1 (glutathione S-transferase mu 1), GSTT1, ERCC2 and ERCC6, were also implicated in our meta-analyses. ..