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Cyclic Nucleotide Phosphodiesterases, Type 4Cyclic Nucleotide Phosphodiesterases, Type 33',5'-Cyclic-AMP PhosphodiesterasesPhosphodiesterase 3 InhibitorsHydrolysisPhosphodiesterase InhibitorsCyclic AMPKineticsAdenosine TriphosphateSubstrate SpecificityCyclic AMP-Dependent Protein KinasesColforsinAdenosine TriphosphatasesMolecular Sequence DataPhosphatidylinositolsGuanosine TriphosphateHydrogen-Ion ConcentrationBinding SitesAmino Acid SequenceCatalysisBucladesineAdenylate CyclaseEscherichia coliPhosphoric Diester HydrolasesEstersAdenosine Diphosphate8-Bromo Cyclic Adenosine MonophosphateProtein BindingCalciumEnzyme ActivationCarboxylic Ester HydrolasesModels, MolecularSignal TransductionCells, CulturedChromatography, High Pressure LiquidCattleSecond Messenger SystemsReceptors, Cyclic AMPProton-Translocating ATPasesCyclic AMP Response Element-Binding ProteinThionucleotidesPhosphatesMagnesiumCell LineType C PhospholipasesBase SequenceProtein ConformationRecombinant ProteinsLipaseMutationCell MembraneCampingInositol PhosphatesBacterial ProteinsStructure-Activity RelationshipCyclic GMPGTP-Binding ProteinsProtein Structure, TertiaryCatalytic DomainGlycoside HydrolasesTemperatureChromatography, Thin LayerPhosphorylationMutagenesis, Site-DirectedGTP PhosphohydrolasesRabbitsAmidohydrolasesRolipramNucleotidesConcentration CampsPhospholipasesPhospholipases A2Enzyme InhibitorsPhospholipases ADiglyceridesAdenylyl ImidodiphosphateTime FactorsDictyosteliumStereoisomerismMagnetic Resonance SpectroscopyDose-Response Relationship, DrugMolecular Structure
Catalyze the hydrolysis of cyclicCatalyzes the hydrolysisPDE4EnzymesPhosphodiesterasesCGMPAdenosinePDEsInflammatoryLipolysisMembraneHormone-sensitIntracellular cAMPEnzymeInflammationMobilizationGlucagonPathwayAdenylate cyclaseCytosolicCatalyticIsoformsPhosphateInducesReceptorPhosphorylationCalciumSignificantlyRegulationSynthesisMechanismsIncludeBreakdownActivityCellsCellHumanPerformanceFormSignalRoleProcessFound
Catalyze the hydrolysis of cyclic2
  • Oocyte arrest at the diplotene stage is maintained in part through the activity of phosphodiesterase enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate (cAMP) into AMP [ 1 , 2 ]. (biomedcentral.com)
  • Our research interests are in the field of cyclic nucleotide signaling and cardiovascular biology, with a particular focus on cyclic nucleotide phosphodiesterases (PDEs) that catalyze the hydrolysis of cyclic nucleotide second messengers (cAMP and cGMP). (rochester.edu)
Catalyzes the hydrolysis1
  • SINETROL® facilitates lipolysis through the inhibition of phosphodiesterase-4 (PDE), the enzyme that catalyzes the hydrolysis (breakdown) of cyclic adenosine monophosphate (cAMP). (pharmafreak.com)
PDE412
  • Piclamilast functions through the selective inhibition of the four PDE4 isoforms (PDE4A-D). It shows no inhibition of the other PDEs. (wikipedia.org)
  • PDE4 hydrolyzes cyclic adenosine monophosphate (cAMP) to inactive adenosine monophosphate (AMP). (wikipedia.org)
  • Inhibition of PDE4 blocks hydrolysis of cAMP thereby increasing levels of cAMP within cells. (wikipedia.org)
  • PDE4 inhibition in an induced chronic lung disease murine model was shown to have anti-inflammatory properties, attenuate pulmonary fibrin deposition and vascular alveolar leakage, and prolong survival in hyperoxia-induced neonatal lung injury. (wikipedia.org)
  • A study of PDE4 inhibition in a murine model of allergic asthma showed that piclamilast significantly improves the pulmonary function, airway inflammation and goblet cell hyperplasia. (wikipedia.org)
  • Inhibition of PDE4 activity recovers the receptor-induced cAMP signal and promotes contractile response in mouse hearts during extended periods of agonist stimulation. (johnshopkins.edu)
  • The full mechanism of action of this drug is not fully established, however, it is known that apremilast is an inhibitor of phosphodiesterase 4 (PDE4), which mediates the activity of cyclic adenosine monophosphate (cAMP), a second messenger. (drugbank.com)
  • 5 The inhibition of PDE4 by apremilast leads to increased intracellular cAMP levels. (drugbank.com)
  • 13 Some other major metabolites, M14 and M16, are significantly less active in the inhibition of PDE4 and inflammatory mediators than their parent drug, apremilast. (drugbank.com)
  • These outcomes suggest that the pool(s) of cAMP regulating androgen production are controlled by PDE8s working in conjunction with PDE4. (ece-inhibitor.com)
  • We further demonstrate that combined inhibition of PDE8s and TCN 201 PDE4 significantly elevated PKA activity TCN 201 including phosphorylation of cholesterol-ester hydrolase (CEH)/hormone-sensitive lipase (HSL). (ece-inhibitor.com)
  • Finally mixed inhibition of PDE8s and PDE4 elevated the appearance of steroidogenic severe regulatory (Superstar) protein. (ece-inhibitor.com)
Enzymes4
  • The phosphodiesterases are enzymes responsible for hydrolysis of cyclic adenosine monophosphate (cAMP), a naturally occurring substance that mediates suppression of inflammatory cell activation. (clinicaltrialsarena.com)
  • 2 The substrate specificities include enzymes that are specific for cyclic AMP hydrolysis, enzymes for cyclic GMP hydrolysis 3 and those that hydrolyse both. (ecrjournal.com)
  • 2001). The substrate specificities include the enzymes which are specific for cAMP hydrolysis, those for cyclic GMP hydrolysis (Mehats et al. (biomedjournal.com)
  • is inclusive of papers focused on stucture, function, and properties of enzymes as well as catalytic and inhibition mechanisms of enzymes, mechanisms of drug action, and related advances on enzymes. (mdpi.com)
Phosphodiesterases4
  • Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl or 8-Br-cAMP, no metabolic side effects. (biolog.de)
  • Phosphodiesterase (PDE) 8A and PDE8B are high-affinity cAMP-specific phosphodiesterases that are highly expressed in Leydig cells. (ece-inhibitor.com)
  • The homeostatic role of phosphodiesterases (PDEs) as related to the intracellular levels of cAMP and cGMP was first described by Sutherland (Sutherland, Rall, 1958) who, due to this, was awarded the Nobel Prize for Physiology and Medicine in 1971. (biomedjournal.com)
  • Phosphodiesterases (PDEs) hydrolyze the phosphodiester bond of cAMP and cGMP to form the inactive 5′-AMP and 5′-GMP. (biomedjournal.com)
CGMP6
  • cAMP and cGMP regulate a wide variety of cardiac functions, from the short-term effects on myocyte contraction/ relaxation to long-term effects such as gene expression and structural remodeling ( Figure 2 ). (rochester.edu)
  • PDE 5 comprises an enzyme superfamily with 11 subfamilies that hydrolyse the phosphodiester bond of cGMP and cyclic adenosine monophosphate (cAMP) to form the inactive 5'-GMP and 5'-AMP. (ecrjournal.com)
  • 6 in the rat aorta, vardenafil but not sildenafil or tadalafil affects serum calcium (Ca++) handling to produce relaxation in addition to the typical increase of cGMP mediated by PDE 5 inhibition. (ecrjournal.com)
  • It has been documented that PDE5 degrades 3C5-cGMP and its inhibition prospects to an increase in intracellular cGMP levels and subsequent activation of protein kinase G, resulting in a decrease in Ca2+ influx and consequent relaxation of smooth muscle tissue [11]. (sipurpashut.net)
  • In optimization of the intracellular levels of cAMP and cGMP, breakdown is predominant over synthesis. (biomedjournal.com)
  • Fertel and Weiss, 1976) therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). (biomedjournal.com)
Adenosine4
  • In hypothalamic neurons, modulators such as neuropeptide Y (NPY) and adenosine depress glutamatergic transmission by either a pertussis toxin (PTx)-sensitive G-protein-coupled pathway or by inhibition of voltage-activated calcium channels (VACCs). (jneurosci.org)
  • Caffeine increases resting energy expenditure and thermogenesis through adenosine receptor blockade and inhibition of phosphodiesterase (PDE), which is why caffeine is synergistic with SINETROL. (pharmafreak.com)
  • Platelet receptors for ADP include the P2Y12 receptor, which sends signals to suppress adenylate cyclase, decreases cyclic adenosine monophosphate (cAMP) levels, and promotes activation of the glycoprotein IIb/IIIa receptor (assembled on the activated platelet surface membrane from glycoproteins IIb and IIIa). (msdmanuals.com)
  • This agent activates hepatic glucagon receptors, which stimulate cyclic adenosine monophosphate (cAMP) synthesis. (medscape.com)
PDEs1
  • Through genetic depletion and pharmacological inhibition, we aim to demonstrate the causative role and address the underlying mechanism of these PDEs in SMC pathology and vascular remodeling using in vitro and in vivo approaches. (rochester.edu)
Inflammatory4
  • cAMP suppresses the activity of immune and inflammatory cells. (wikipedia.org)
  • By inhibiting PDE-IV, drugs such as Ariflo increase levels of cAMP and reduce inflammatory cell activation in the respiratory tract. (clinicaltrialsarena.com)
  • 14 An increase in cAMP results in the suppression of inflammation by decreasing the expression of TNF-α, IL-17, IL-23, and other inflammatory mediators. (drugbank.com)
  • The activated AMPK might provide protective benefits in HIRI via prevention of energy decline, inhibition of inflammatory response, suppression of hepatocyte apoptosis and attenuation of oxidative stress. (drrestivo.com)
Lipolysis4
  • PhD Sinetrol + helps stimulate lipolysis* through the inhibition of phosphodiesterase 4 (PDE-4) 3,4, the enzyme that catalyses the hydrolysis of cAMP. (t-nutrition.com)
  • This agent accelerates hepatic glycogenolysis and lipolysis in adipose tissue by stimulating cyclic AMP (cAMP) synthesis via adenylyl cyclase and enhancing phosphorylase kinase activity. (medscape.com)
  • Lipolysis is the metabolic process through which triacylglycerols (TAGs) break down via hydrolysis into their constituent molecules: glycerol and free fatty acids (FFAs). (imingo.net)
  • During lipolysis, intracellular TAG undergoes hydrolysis through the action of three major lipases: adipose triglyceride lipase (ATGL/desnutrin/phospholipase A2ζ), HSL, and monoacylglycerol (MGL) lipase. (imingo.net)
Membrane1
  • Membrane permeability comparable to 8-Br-cAMP. (biolog.de)
Hormone-sensit1
  • SCIRP: Food and Nutrition Sciences, Vol. In this process, both in vivoand in cultur… This binding will likewise lead to the cAMP/PKA-led phosphorylation of hormone sensitive lipase, that will ultimately drive the release of free fatty acids and glycerol. (imingo.net)
Intracellular cAMP1
  • In these cells testosterone creation is predominantly governed through connections of luteinizing hormone (LH) using its receptor leading to elevated intracellular cAMP and following activation of PKA. (ece-inhibitor.com)
Enzyme2
  • The aggregative enzyme (ACA) is activated following cAMP-binding to the G-protein coupled cell surface cAMP receptor (cAR1). (biomedcentral.com)
  • Within certain cells the enzyme adenylate cyclase makes cAMP from ATP, and typically this reaction is regulated by hormones such as adrenaline or glucagon. (drrestivo.com)
Inflammation1
  • Vinpocetine Suppresses Streptococcus pneumoniae-Induced Inflammation via Inhibition of ERK1 by CYLD. (rochester.edu)
Mobilization1
Glucagon2
  • Glucagon also increases hydrolysis of glycogen to glucose (glycogenolysis) in the liver. (medscape.com)
  • Octreotide acts primarily on somatostatin receptor subtypes II and V. It also inhibits growth hormone secretion and has a multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, vasoactive intestinal peptides (VIP), and gastrointestinal peptides. (medscape.com)
Pathway5
  • Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases. (rndsystems.com)
  • This allows the coupling of ATP binding and hydrolysis to electron transfer against a redox potential gradient and metal incorporation to (re)activate one of the central players of the pathway. (degruyter.com)
  • Launch The cAMP-dependent proteins kinase (PKA) signaling pathway can be an important regulator of several different physiological procedures including hormone-stimulated steroidogenesis. (ece-inhibitor.com)
  • The cAMP/PKA signaling pathway is normally a more developed regulator of androgen creation in Leydig cells. (ece-inhibitor.com)
  • 2009 Arousal from the cAMP/PKA pathway network marketing leads to a rise in both amounts and activity of Superstar proteins (Arakane et al. (ece-inhibitor.com)
Adenylate cyclase1
Cytosolic1
  • 10-fold) more sensitive (IC50 0.02 μM) to rolipram inhibition than its cytosolic form (IC50 0.2 μM). (ox.ac.uk)
Catalytic1
  • It is suggested that these alternatively spliced regions determine changes in the maximal catalytic activity of the isoforms, their susceptibility to inhibition by rolipram and mode of interaction with particulate fractions. (ox.ac.uk)
Isoforms1
Phosphate4
  • 1961. The reactions of organic phosphate: Part V. The hydrolysis of triphenyl and trimethyl phosphates. (cdc.gov)
  • Enzymatic hydrolysis of nucleoside diphosphates and p-nitrophenyl phosphate in normal and cortisone-treated rats. (taljedal.se)
  • Hydrolysis of GTP takes place via an in-line attack of a water molecule at the -phosphate. (forexsignalx.com)
  • AMP may be produced by the hydrolysis of one high energy phosphate bond of ADP. (drrestivo.com)
Induces1
  • cAMP-dependent protein kinase (PKA) phosphorylates cAMP response element binding protein (CREB), a transcription factor, which induces the synthesis of certain genes including C-Fos . (wikidoc.org)
Receptor4
  • Here, using live cell imaging of cAMP with a FRETbased biosensor and myocyte contraction assay, we show that the catecholamine-activated β 1 adrenergic receptor ( β 1 AR) continuously stimulates second messenger cAMP synthesis in primary cardiac myocytes and neurons, which lasts for more than 8 h (a decay t 1/2 of 3.9 h) in cardiac myocytes. (johnshopkins.edu)
  • However, the β 1 AR-induced cAMP signal is counterbalanced and masked by the receptor-bound phosphodiesterase (PDE) 4D8-dependent cAMP hydrolysis. (johnshopkins.edu)
  • Together, these findings unveil a long lasting adrenergic signal in neurons and myocytes under prolonged stimulation and an underappreciated role of PDE that is essential in classic receptor signaling desensitization and in maintaining a long lasting cAMP equilibrium for ligand-induced physiological response. (johnshopkins.edu)
  • 1986). The 5-HT2A receptor was also the very first 5-HT receptor found to couple to stimulate phosphatidyl inositol hydrolysis (Conn and SandersBush, 1984). (adenylate-cyclase.com)
Phosphorylation1
  • Knockdown of SAP97 or mutation of the β 1 AR PDZ motif disrupts the complex and promotes sustained agonist-induced cAMP activity, PKA phosphorylation, and cardiac myocyte contraction response. (johnshopkins.edu)
Calcium2
  • The inhibition could be mimicked by the L-type calcium channel blocker nimodipine (1 μ m ) as well as by protein kinase C (PKC) activators phorbol 12,13-dibutyrate (10 μ m ) and phorbol 12-myristate 13-acetate (500 n m ), and blocked by the PKC inactivator (±)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine (200 μ m ), suggesting a mechanism involving PKC modulation of L-type calcium channels. (jneurosci.org)
  • The investigators found that the resultant transfected cells showed defects in ATP2A2 protein expression (15 mutants), ATP hydrolysis (29 mutants), calcium transport (4 mutants), and calcium binding and kinetics (3 mutants). (medscape.com)
Significantly1
  • Inhibition of nuclear meiotic maturation via IBMX significantly increased MIR21 and decreased its target, PDCD4. (biomedcentral.com)
Regulation2
  • Our research programs have been among the pioneers in elucidating the function, regulation, and underlying mechanism of different PDE activation/ inhibition in the pathogenesis of cardiovascular diseases. (rochester.edu)
  • They depicted schematic graphs showing a model for PDE5 inhibition regulation and bone homeostasis. (sipurpashut.net)
Synthesis1
  • In accord with our hypothesis that the link from Ca 2+ to cAMP synthesis is mediated by a Ca 2+ -dependent phospholipase C we found that W-7 was not active in the phospholipase C knockout mutant. (biomedcentral.com)
Mechanisms1
  • It was recognised that papaverine and pentoxifylline mediated vasorelaxation by a number of mechanisms including non-selective PDE inhibition and these drugs can be considered as forerunners to the clinically successful PDE5 inhibitors used today for the treatment of erectile dysfunction. (biomedjournal.com)
Include1
  • Apremilast is heavily metabolized by various pathways, which include oxidation, hydrolysis, in addition to conjugation. (drugbank.com)
Breakdown1
  • Higher levels of cAMP result in an increased rate of fat breakdown and fat loss. (pharmafreak.com)
Activity1
  • The inhibition of the proton pump by W-7 causes a leakage of Ca 2+ that indirectly stimulates adenylyl cyclase activity via phospholipase C. (biomedcentral.com)
Cells3
  • 5ʹ-Rapid amplification of cDNA ends, done on poly(A)+ RNA from human U87 cells, was used to identify 420 bp of novel 5ʹ sequence of a PDE4B cAMP-specific phosphodiesterase (PDE). (ox.ac.uk)
  • During early differentiation of Dictyostelium the attractant cAMP is released periodically to induce aggregation of the cells. (biomedcentral.com)
  • 2009 General the degrees of cAMP in response to arousal by human hormones are firmly correlated with the best price of steroid creation by Leydig cells. (ece-inhibitor.com)
Cell1
  • cAMP is secreted periodically after about 4 h of differentiation with a period length in cell suspension of about 7 min. (biomedcentral.com)
Human2
  • Steady-state inhibition data show that huprine X binds to human AChE and Torpedo AChE 28- and 54-fold, respectively, more tightly than tacrine. (proteopedia.org)
  • 1995). The human promoter sequence contains several transcription initiation internet sites, together with a number of binding web pages for transcription components, including simian virus 40 promoter element 1, polyomavirus enhancer activator three, cAMP response element, and E-box binding proteins. (adenylate-cyclase.com)
Performance1
  • It will be specially focused on: (a) characteristics of the different substrates used for measuring PON1, with emphasis in four aspects: toxicity, polymorphism influence, rate of hydrolysis and diagnostic performance. (biomedcentral.com)
Form1
  • Sp-cAMPS is also available in a highly purified form as sodium salt ( A 003 S High Purity Grade ). (biolog.de)
Signal1
Role2
  • Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis. (rndsystems.com)
  • cAMP plays an important role in intracellular signalling. (drrestivo.com)
Process1
  • The process is reversed by the alpha subunit, which hydrolyses GTP to GDP followed by reformation of the Gα i (GDP)βγ complex. (elifesciences.org)
Found1
  • We found that the calmodulin antagonist W-7 transiently enhanced cAMP spikes. (biomedcentral.com)