A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.
Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.
A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.
A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.
A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), members of this class have additional specificity for CYCLIC GMP.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A phosphodiesterase 4 inhibitor with antidepressant properties.
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The rate dynamics in chemical or physical systems.
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Compounds that specifically inhibit PHOSPHODIESTERASE 3.
Compounds that specifically inhibit PHOSPHODIESTERASE 4.
Inhibitor of phosphodiesterases.
N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Compounds that specifically inhibit PHOSPHODIESTERASE 5.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The process of cleaving a chemical compound by the addition of a molecule of water.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
Purine bases found in body tissues and fluids and in some plants.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. (1/531)

The extracellular receptor stimulated kinase ERK2 (p42(MAPK))-phosphorylated human cAMP-specific phosphodiesterase PDE4D3 at Ser579 and profoundly reduced ( approximately 75%) its activity. These effects could be reversed by the action of protein phosphatase PP1. The inhibitory state of PDE4D3, engendered by ERK2 phosphorylation, was mimicked by the Ser579-->Asp mutant form of PDE4D3. In COS1 cells transfected to express PDE4D3, challenge with epidermal growth factor (EGF) caused the phosphorylation and inhibition of PDE4D3. This effect was blocked by the MEK inhibitor PD98059 and was not apparent using the Ser579-->Ala mutant form of PDE4D3. Challenge of HEK293 and F442A cells with EGF led to the PD98059-ablatable inhibition of endogenous PDE4D3 and PDE4D5 activities. EGF challenge of COS1 cells transfected to express PDE4D3 increased cAMP levels through a process ablated by PD98059. The activity of the Ser579-->Asp mutant form of PDE4D3 was increased by PKA phosphorylation. The transient form of the EGF-induced inhibition of PDE4D3 is thus suggested to be due to feedback regulation by PKA causing the ablation of the ERK2-induced inhibition of PDE4D3. We identify a novel means of cross-talk between the cAMP and ERK signalling pathways whereby cell stimuli that lead to ERK2 activation may modulate cAMP signalling.  (+info)

Phosphorylation-mediated activation and translocation of the cyclic AMP-specific phosphodiesterase PDE4D3 by cyclic AMP-dependent protein kinase and mitogen-activated protein kinases. A potential mechanism allowing for the coordinated regulation of PDE4D activity and targeting. (2/531)

In this study, we describe a novel mechanism by which a protein kinase C (PKC)-mediated activation of the Raf-extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) cascade regulates the activity and membrane targeting of members of the cyclic AMP-specific phosphodiesterase D family (PDE4D). Using a combination of pharmacological and biochemical approaches, we show that increases in intracellular cAMP cause a protein kinase A-mediated phosphorylation and activation of the two PDE4D variants expressed in vascular smooth muscle cells, namely PDE4D3 and PDE4D5. In addition, we show that stimulation of PKC via the associated activation of the Raf-MEK-ERK cascade results in the phosphorylation and activation of PDE4D3 in these cells. Furthermore, our studies demonstrate that simultaneous activation of both the protein kinase A and PKC-Raf-MEK-ERK pathways allows for a coordinated activation of PDE4D3 and for the translocation of the particulate PDE4D3 to the cytosolic fraction of these cells. These data are presented and discussed in the context of the activation of the Raf-MEK-ERK cascade acting to modulate the activation and subcellular targeting of PDE4D gene products mediated by cAMP.  (+info)

IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells. (3/531)

In FDCP2 myeloid cells, IL-4 activated cyclic nucleotide phosphodiesterases PDE3 and PDE4, whereas IL-3, granulocyte-macrophage CSF (GM-CSF), and phorbol ester (PMA) selectively activated PDE4. IL-4 (not IL-3 or GM-CSF) induced tyrosine phosphorylation of insulin-receptor substrate-2 (IRS-2) and its association with phosphatidylinositol 3-kinase (PI3-K). TNF-alpha, AG-490 (Janus kinase inhibitor), and wortmannin (PI3-K inhibitor) inhibited activation of PDE3 and PDE4 by IL-4. TNF-alpha also blocked IL-4-induced tyrosine phosphorylation of IRS-2, but not of STAT6. AG-490 and wortmannin, not TNF-alpha, inhibited activation of PDE4 by IL-3. These results suggested that IL-4-induced activation of PDE3 and PDE4 was downstream of IRS-2/PI3-K, not STAT6, and that inhibition of tyrosine phosphorylation of IRS molecules might be one mechnism whereby TNF-alpha could selectively regulate activities of cytokines that utilized IRS proteins as signal transducers. RO31-7549 (protein kinase C (PKC) inhibitor) inhibited activation of PDE4 by PMA. IL-4, IL-3, and GM-CSF activated mitogen-activated protein (MAP) kinase and protein kinase B via PI3-K signals; PMA activated only MAP kinase via PKC signals. The MAP kinase kinase (MEK-1) inhibitor PD98059 inhibited IL-4-, IL-3-, and PMA-induced activation of MAP kinase and PDE4, but not IL-4-induced activation of PDE3. In FDCP2 cells transfected with constitutively activated MEK, MAP kinase and PDE4, not PDE3, were activated. Thus, in FDCP2 cells, PDE4 can be activated by overlapping MAP kinase-dependent pathways involving PI3-K (IL-4, IL-3, GM-CSF) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase independent (but perhaps IRS-2/PI3-K dependent).  (+info)

The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform. (4/531)

The WD-repeat protein receptor for activated C-kinase (RACK1) was identified by its interaction with the cyclic AMP-specific phosphodiesterase (PDE4) isoform PDE4D5 in a yeast two-hybrid screen. The interaction was confirmed by co-immunoprecipitation of native RACK1 and PDE4D5 from COS7, HEK293, 3T3-F442A, and SK-N-SH cell lines. The interaction was unaffected by stimulation of the cells with the phorbol ester phorbol 2-myristate 3-acetate. PDE4D5 did not interact with two other WD-repeat proteins, beta'-coatomer protein and Gsbeta, in two-hybrid tests. RACK1 did not interact with other PDE4D isoforms or with known PDE4A, PDE4B, and PDE4C isoforms. PDE4D5 and RACK1 interacted with high affinity (Ka approximately 7 nM) [corrected] when they were expressed and purified from Escherichia coli, demonstrating that the interaction does not require intermediate proteins. The binding of the E. coli-expressed proteins did not alter the kinetics of cAMP hydrolysis by PDE4D5 but caused a 3-4-fold change in its sensitivity to inhibition by the PDE4 selective inhibitor rolipram. The subcellular distributions of RACK1 and PDE4D5 were extremely similar, with the major amount of both proteins (70%) in the high speed supernatant (S2) fraction. Analysis of constructs with specific deletions or single amino acid mutations in PDE4D5 demonstrated that a small cluster of amino acids in the unique amino-terminal region of PDE4D5 was necessary for its interaction with RACK1. We suggest that RACK1 may act as a scaffold protein to recruit PDE4D5 and other proteins into a signaling complex.  (+info)

Effects of XT-44, a phosphodiesterase 4 inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and its therapeutic effects in rat osteopenia models. (5/531)

We have reported that denbufylline, a phosphodiesterase 4 (PDE4) inhibitor, inhibits bone loss in Walker256/S tumor-bearing rats, suggesting therapeutic potentiality of a PDE4 inhibitor in osteopenia. In the present study, effects of a new PDE4 inhibitor, 1-n-butyl-3-n-propylxanthine (XT-44), in bone were evaluated in cell cultures and animal experiments. In rat bone marrow culture, XT-44 stimulated mineralized-nodule formation, whereas it inhibited osteoclast-like cell formation in mouse bone marrow culture. In Walker256/S-bearing rats (6-week-old female Wistar Imamichi rats), rapid decrease in bone mineral density (BMD) was prominent, and oral administration of XT-44 (0.3 mg/kg, every 2 days) inhibited the decrease in BMD. In the second animal experiment, female Wistar rats (6-week-old) were sciatic neurectomized, and XT-44 was orally administered to these rats every 2 days for 4 weeks. XT-44 administration (0.3 mg/kg) recovered BMD in these neurectomized animals. Furthermore, 19-week-old, female Wistar rats were ovariectomized (OVX), and 15 weeks after surgery, these rats were orally administered XT-44 every 2 days for 8 weeks. XT-44 treatment (1 mg/kg) increased the BMD of OVX rats. These results indicate that XT-44 could be a candidate as a therapeutic drug for treating osteopenia including osteoporosis.  (+info)

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytes. (6/531)

The effects of several phosphodiesterase (PDE) inhibitors on the L-type Ca current (I(Ca)) and intracellular cyclic AMP concentration ([cAMP]i) were examined in isolated rat ventricular myocytes. The presence of mRNA transcripts encoding for the different cardiac PDE subtypes was confirmed by RT-PCR. IBMX (100 microM), a broad-spectrum PDE inhibitor, increased basal I(Ca) by 120% and [cAMP]i by 70%, similarly to a saturating concentration of the beta-adrenoceptor agonist isoprenaline (1 microM). However, MIMX (1 microM), a PDE1 inhibitor, EHNA (10 microM), a PDE2 inhibitor, cilostamide (0.1 microM), a PDE3 inhibitor, or Ro20-1724 (0.1 microM), a PDE4 inhibitor, had no effect on basal I(Ca) and little stimulatory effects on [cAMP]i (20-30%). Each selective PDE inhibitor was then tested in the presence of another inhibitor to examine whether a concomitant inhibition of two PDE subtypes had any effect on I(Ca) or [cAMP]i. While all combinations tested significantly increased [cAMP]i (40-50%), only cilostamide (0.1 microM)+ Ro20-1724 (0.1 microM) produced a significant stimulation of I(Ca) (50%). Addition of EHNA (10 microM) to this mix increased I(Ca) to 110% and [cAMP]i to 70% above basal, i.e. to similar levels as obtained with IBMX (100 microM) or isoprenaline (1 microM). When tested on top of a sub-maximal concentration of isoprenaline (1 nM), which increased I(Ca) by (approximately 40% and had negligible effect on [cAMP]i, each selective PDE inhibitor induced a clear stimulation of [cAMP]i and an additional increase in I(Ca). Maximal effects on I(Ca) were approximately 8% for MIMX (3 microM), approximately 20% for EHNA (1-3 microM), approximately 30% for cilostamide (0.3-1 microM) and approximately 50% for Ro20-1724 (0.1 microM). Our results demonstrate that PDE1-4 subtypes regulate I(Ca) in rat ventricular myocytes. While PDE3 and PDE4 are the dominant PDE subtypes involved in the regulation of basal I(Ca), all four PDE subtypes determine the response of I(Ca) to a stimulus activating cyclic AMP production, with the rank order of potency PDE4>PDE3>PDE2>PDE1.  (+info)

A comparison of the inhibitory activity of PDE4 inhibitors on leukocyte PDE4 activity in vitro and eosinophil trafficking in vivo. (7/531)

1. Phosphodiesterase (PDE) 4 inhibitors have been shown to inhibit eosinophil PDE4 activity in vitro and accumulation of eosinophils in experimental airways inflammation. However, direct effects on eosinophil trafficking have not been studied in detail and it is not known if activity in vitro translates into efficacy in vivo. In the present study, we compared the activity of five PDE4 inhibitors in vitro and against trafficking of (111)In-eosinophils in cutaneous inflammation in the guinea-pig. 2. The rank order of potency for inhibition of PDE4 activity in guinea-pig eosinophil, neutrophil and macrophage, and human neutrophil lysates was RP73401 > SB207499 >CDP840 > rolipram > LAS31025. On TNFalpha production by human PBMC, all inhibitors with the exception of rolipram showed potency similar to their effect on neutrophil lysates. 3. In a brain cerebellum binding assay, the rank order of potency at displacing [3H]-rolipram was RP73401 > rolipram > SB207499 > CDP840 > LAS30125. 4. Trafficking of (111)In-eosinophils to skin sites injected with PAF, ZAP or antigen in sensitized sites was inhibited by oral administration of all PDE4 inhibitors. The rank order of potency was RP73401 = rolipram > LAS31025 > SB207499 > CDP840. 5. With the exception was RP73401, which was the most potent compound in all assays, there was no clear relationship between activity of PDE4 inhibitors in vitro and capacity to inhibit eosinophil trafficking in vivo. Thus, we conclude that in vitro activity of PDE4 inhibitors does not predict in vivo efficacy in an experimental model of eosinophil trafficking.  (+info)

Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin. (8/531)

The effects of acylation-stimulating protein (ASP) and insulin on free fatty acid (FFA) release from isolated human fat cells and the signal transduction pathways to induce these effects were studied. ASP and insulin inhibited basal and norepinephrine-induced FFA release by stimulating fractional FFA re-esterification (both to the same extent) and by inhibiting FFA produced during lipolysis (ASP to a lesser extent than insulin). Protein kinase C inhibition influenced none of the effects of ASP or insulin. Phosphatidylinositol 3-kinase inhibition counteracted the effects of insulin but not of ASP. Phosphodiesterase 3 (PDE3) activity was stimulated by ASP and insulin, whereas PDE4 activity was slightly increased by ASP only. Selective PDE3 inhibition reversed the effects of both ASP and insulin on fractional FFA re-esterification and lipolysis. Selective PDE4 inhibition slightly counteracted the ASP but not the effect of insulin on fractional FFA re-esterification and did not prevent the action of ASP or insulin on lipolysis. Thus, ASP and insulin play a major role in regulating FFA release from fat cells as follows: insulin by stimulating fractional FFA re-esterification and inhibiting lipolysis and ASP mainly by stimulating fractional FFA re-esterification. For both ASP and insulin these effects on FFA release are mediated by PDE3, and for ASP PDE4 might also be involved. The signaling pathway preceding PDE is not known for ASP but involves phosphatidylinositol 3-kinase for insulin.  (+info)

We isolated a human cAMP-specific phosphodiesterase (PDE7B) cDNA from human caudate nucleus. The human PDE7B was composed of 450 amino acid residues with a molecular mass of 51,835 Da. The deduced amino acid sequence of human PDE7B was 64.1% identical to that of human PDE7A (67.1% identity in the ca …
As mentioned above, RyRs are often complexed with several accessory proteins, forming an intricate multi-protein array [32, 33]. The best known RyR-interacting proteins are CaM, which tonically inhibits RyR2 activity and produces biphasic effects on RyR1 [34, 35]; FKBP12 and FKBP12.6, which stabilize RyR1 and RyR2 closures [36-38]; and the ternary complex triadin-junctin-calsequestrin, which senses luminal Ca2+ content and modulates RyR activity by acting either as a Ca2+ reservoir or as a direct channel ligand [39-47]. More recently, RyR2 has been found to hold anchoring sites for protein kinase (PK)A, protein phosphatase (PP)1, the cAMP-specific phosphodiesterase (PDE)4D3 and Ca2+/calmodulin-dependent protein kinase (CaMK)II [37, 48], emphasizing the importance of RyR2 regulation by phosphorylation [32]. In cardiac cells, sorcin exerts protein-protein interactions with the RyR and inhibits Ca2+ release in a Ca2+-dependent manner [49, 50].. The binding sites of several regulatory proteins ...
cAMP-specific phosphodiesterases (PDE) comprise an extensive family of enzymes that control intracellular levels of cAMP and thus regulate T cell responses. It is not known how the function of these enzymes is altered by TCR engagement. We have examined this issue by studying one of the PDE isozymes (PDE4B). PDE4B RNA and protein were detected in resting PBLs, and the levels of PDE4B protein increased with cell cycling. In peripheral blood T cells, two previously reported PDE4B isoforms could be detected: one was 75-80 kDa (PDE4B1) and the other was 65-67 kDa (PDE4B2). These two isoforms differed in their N-terminal sequence, with the presence of four potential myristylation sites in the PDE4B2 that are absent in PDE4B1. Consequently, only PDE4B2 was found in association with the CD3{varepsilon} chain of the TCR. In addition, although both isoforms were phosphorylated in tyrosines in pervanadate-stimulated T cells, only the TCR-associated PDE4B2 was tyrosine-phosphorylated following CD3 ligation. The
References for Abcams Recombinant human PDE7B protein (ab79800). Please let us know if you have used this product in your publication
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cAMP-specific 3,5-cyclic phosphodiesterase 4C is an enzyme that in humans is encoded by the PDE4C gene. PDE4C is predominantly found in peripheral tissues. GRCh38: Ensembl release 89: ENSG00000105650 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: PDE4C phosphodiesterase 4C, cAMP-specific (phosphodiesterase E1 dunce homolog, Drosophila). Zhang, HT (2009). Cyclic AMP-Specific Phosphodiesterase-4 as a Target for the Development of Antidepressant Drugs. Current Pharmaceutical Design. 15 (14): 1688-1698. doi:10.2174/138161209788168092. PMID 19442182. Engels P, Sullivan M, Müller T, Lübbert H (1995). Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C). FEBS Lett. 358 (3): 305-10. doi:10.1016/0014-5793(94)01460-I. PMID 7843419. Milatovich A, Bolger G, Michaeli T, Francke U (1994). Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse. Somat. Cell Mol. ...
We have analyzed the brain distribution of the rat cAMP-specific phosphodiesterases (rPDEIV) which are closely related to the defective gene products of the drosophila melanogaster learning and memory mutant dunce. PCR analysis of rat brain cDNA was performed on the four known dunce-like cAMP PDE rat isogenes (rPDE-IV-A, -B, -C, -D). High expression of three of these isogenes (rPDEIV-A, -B, -D) highlighted their involvement in regulation of cAMP in the brain. Specific probes for all four isogenes were then used for in situ hybridization of rat brain sections. Distinct but overlapping expression patterns were observed for rPDEIV-A, rPDEIV-B, and rPDEIV-D. Abundant expression of these subtypes was observed in the olfactory system, the hippocampus and the cerebellum, while no specific signals could be detected in most areas of the brain for the subtype rPDEIV-C.
Moracin M, a phenolic component in the skin of Morus alba L., is a potent phosphodiesterase-4 (PDE4) inhibitor with IC50 values of 2.9, 4.5, >40, and >100 μM for PDE4D2, PDE4B2, PDE5A1, and PDE9A2, respectively. Moracin M has anti-inflammatory activity. - Mechanism of Action & Protocol.
The small heat shock protein HSP20 is known to be cardioprotective during times of stress and the mechanism underlying its protective abilities depends on its phosphorylation on Ser16 by PKA (protein kinase A). Although the external stimuli that trigger Ser16 phosphorylation have been well studied, the events that modulate spatial and temporal control of this modification remain to be clarified. Here, we report that inhibition of cAMP phosphodiesterase-4 (PDE4) induces the phosphorylation of HSP20 in resting cardiac myocytes and augments its phosphorylation by PKA following β-adrenergic stimulation. Moreover, using peptide array technology, in vitro binding studies, co-immunoprecipitation techniques and immunocytochemistry, we show that HSP20 binds directly to PDE4 within a region of the conserved catalytic domain. We also show that FRET-based, genetically-encoded cAMP reporters anchored to HSP20 exhibit a larger response to PDE4 inhibition compared to free cytosolic cAMP reporters, suggesting that the
A number of novel drugs under development may prove to have a role in the management of asthma. Phosphodiesterase (PDE)4 inhibitors have immunomodulatory effects over a number of inflammatory cells potentially relevant to the treatment of severe asthma [56]. High doses of phosphodiesterase (PDE)4 inhibitors may be necessary to treat severe asthma, and gastro-intestinal side effects may limit their use [56-58], although inhaled PDE4 inhibitors may improve their therapeutic index [59, 60]. Inhibition of protein kinases such as p38 mitogen-activated protein kinase (MAPK) and other tyrosine kinases involved in cellular signalling of pro-inflammatory cytokines may have a role in the treatment of severe asthma [61-63]. For example, a phase 3 study evaluating a tyrosine kinase inhibitor of the c-KIT receptor masitinib commenced recently.. Several drugs licensed for treating other conditions may also have a role in the management of asthma. In a randomized controlled trial of 58 patients with severe ...
cAMP PDEs are emerging as a promising class of drug targets in asthma and cardiovascular disease therapeutic areas. HDB has established the cell-based screening assay for cAMP phosphodiesterase (PDE) inhibitors in HDB based on the Codex ACTOne™ technology. The specificity of the assay has been verified by known PDE inhibitors. Only PDE4 and pan-PDE inhibitors showed positive signals in the cell line that was optimized ...
Shukla, Arun K. and Pyne, Nigel J. (2018) Cellular Signalling - Special issue to celebrate 75th birthday of Prof. Robert J. Lefkowitz. Cellular Signalling, 41. p. 1. ISSN 1873-3913 MacRitchie, Neil and Volpert, Giora and Al Washih, Mohammed and Watson, David G. and Futerman, Anthony H. and Kennedy, Simon and Pyne, Susan and Pyne, Nigel (2016) Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodeling in a hypoxic model of pulmonary arterial hypertension. Cellular Signalling, 28 (8). pp. 946-955. ISSN 1873-3913 Bolger, Graeme B. and Dunlop, Allan J. and Meng, Dong and Day, Jon P. and Klussmann, Enno and Baillie, George S. and Adams, David R. and Houslay, Miles D. (2015) Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains. Cellular Signalling, 27 (4). pp. 756-769. ISSN 1873-3913 Ohotski, Jan and Rosen, Hugh and Bittman, Robert and Pyne, Susan and Pyne, Nigel J (2014) ...
Ariflo (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: from concept to clinic
EXAMPLE 66. ANALYSIS of CONNECTIONS. PDE 10 biochemical analysis. Fosfodiesterazu (PDE) analysis was performed using recombinant human PDE 1A3, 2A3, 3 catalytic phase, 4 catalytic site, 5 catalytic site, 7A, 8A, 9A2, 10A1 11A1 and the enzymes expressed in a baculovirus system using Sf9 cells. PDE activity was measured using a modification of the two-stage method of Thompson and Appleman, described above, which is adapted to format 96-well plates. The effect of PDE inhibitors was determined by study of a fixed amount of enzyme in the presence of concentrations of the test compounds and concentrations of the substrate is smaller than Kmso that Ki was equal to IC50. The final volume for analysis was 110 μl with buffer (10 mm MgCl2; 40 mm Tris·HCl; pH 7,4). The reaction was started with the enzyme and withstood C (3H)-�stratum and substance for 20 minutes at 30°C. The reaction was stopped by denaturation of the enzyme (heating the reaction mixture at 70°C for 2 minutes). Then the reaction ...
The administration of many PDE4 inhibitors has been associated with the side effect of nausea and vomiting. These debilitating adverse events are a significant issue in the therapeutic use of PDE4 inhibitors. Consequently the improvement of the therapeutic window of new generations of PDE4 inhibitors has been a major challenge. It has been previously suggested that the activity on the HARBS of PDE4 correlates with the side effects of emesis and that, hence, PDE4 inhibitors exhibiting a reduced activity on this conformer should have attenuated side effects (13, 15, 31). However, it has now been clarified that the HARBS coincides with the holoenzyme responsible for PDE4 catalysis (11, 12).. An alternative approach to improving the therapeutic index of new generations of PDE4 inhibitors would be to design PDE4 subtype-selective inhibitors, if it could be shown that nausea and vomiting are dependent on a specific PDE4 subtype. The recent demonstration that the emetic potential of PDE4 inhibitors can ...
The 2020 Gordon Research Seminar on Cyclic Nucleotide Phosphodiesterases (GRS) will be held in Les Diablerets, Switzerland. Apply today to reserve your spot.
Looking for online definition of phosphodiesterase 4D, cAMP-specific in the Medical Dictionary? phosphodiesterase 4D, cAMP-specific explanation free. What is phosphodiesterase 4D, cAMP-specific? Meaning of phosphodiesterase 4D, cAMP-specific medical term. What does phosphodiesterase 4D, cAMP-specific mean?
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Emphasizes the integration of major areas of drug discovery and their importance in candidate evaluation It is believed that selecting the «right» drug candidate for development is the key to success. In the last decade, pharmaceutical R&D departments have integrated pharmacokinetics and drug metabolism, pharmaceutics, and toxicology into early drug discovery to improve the assessment of potential drug compounds. Now, Evaluation of Drug Candidates for Preclinical Development provides a complete view and understanding of why absorption-distribution-metabolism-excretion-toxicology (ADMET) plays a pivotal role in drug discovery and development. Encompassing the three major interrelated areas in which optimization and evaluation of drug developability is most critical-pharmacokinetics and drug metabolism, pharmaceutics, and safety assessment-this unique resource encourages integrated thinking in drug discovery. The contributors to this volume: Cover drug transporters, cytochrome P-450 and ...
The elevation of intracellular cyclic AMP by phosphodiesterase (PDE)4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibt eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo ...
Since cAMP blocks meiotic maturation of mammalian and amphibian oocytes in vitro and cyclic nucleotide phosphodiesterase 3A (PDE3A) is primarily responsible for oocyte cAMP hydrolysis, we generated PDE3A-deficient mice by homologous recombination. The Pde3a-/- females were viable and ovulated a normal number of oocytes but were completely infertile, because ovulated oocytes were arrested at the germinal vesicle stage and, therefore, could not be fertilized. Pde3a-/- oocytes lacked cAMP-specific PDE activity, contained increased cAMP levels, and failed to undergo spontaneous maturation in vitro (up to 48 hours). Meiotic maturation in Pde3a-/- oocytes was restored by inhibiting protein kinase A (PKA) with adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS) or by injection of protein kinase inhibitor peptide (PKI) or mRNA coding for phosphatase CDC25, which confirms that increased cAMP-PKA signaling is responsible for the meiotic blockade. Pde3a-/- oocytes that underwent germinal ...
TY - JOUR. T1 - Elevated cAMP-phosphodiesterase in atopic disease. T2 - Cause or effect?. AU - Townley, Robert G.. PY - 1993. Y1 - 1993. UR - http://www.scopus.com/inward/record.url?scp=0027415679&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0027415679&partnerID=8YFLogxK. M3 - Editorial. VL - 121. SP - 15. EP - 17. JO - Translational Research. JF - Translational Research. SN - 1931-5244. IS - 1. ER - ...
liver failure, multiple sclerosis, cialis without prescription In particular, sildenafil has greater than 4,000-fold selectivity for PDE5 over PDE3, The cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility is of particular importance given the known cardiovascular activity of PDE3 inhibitors... at the base of the therapy in progress, the Drugs inhibitors â the enzyme P450 ne levitra online previously mentioned. The tool in question Is a stoneâstructured interview SIEDY (Structured.. with other conditions associated with aging. This assumption viagra 50mg A number of survey on attitudes to ED have been reported... excluding age & gender viagra online purchase opportunity for patient education... • Local Therapy order viagra recent stroke or heart attack of this type are also excluded... administered with a frequency of 120 per minute with a total of endothelial (VEFG) [Vardi et al. 2012; Young and Dyson, 1990]. viagra a stimulus that it Is not set. Not the ...
Characterization of two human cAMP-specific phosphodiesterase subtypes expressed in baculovirus-infected insect cells. (pages 477-484). Bernard Y. Amegadzie, Charles R. Hanning, Megan M. McLaughlin, Miriam Burman, Lenora B. Cieslinski, George P. Livi and Theodore J. Torphy. Version of Record online: 2 JAN 2013 , DOI: 10.1006/cbir.1995.1091. ...
A tonic PKA activity is maintained by adenylyl cyclase-dependent cAMP production and PDE-dependent cAMP hydrolysis.19,26 Our results show that PDE4 is the major enzyme that controls local PKA activity along the sarcolemma, whereas PDE3 mediates primarily cAMP hydrolysis on the myofilaments (Figure 5). In agreement, both PDE4D and PDE4B display overlap with the membrane marker caveolin-3 (Online Figure II), consistent with a recent report showing that both enzymes have a binding motif to caveolin-3;27 loss of caveolin-3 may lead to loss of PDE4 activity at the sarcolemma. In contrast, PDE3 displays a colocalization with myofibrils (Online Figure II), supporting its primary role in controlling local cAMP and PKA activity there (Figure 5). Meanwhile, we observe a high tonic PKA activity on the myofilaments, which is consistent with a relatively high PKA phosphorylation of myosin-binding protein C and TnI in healthy cardiac tissues.28. Although the PKA activity is usually depressed in the late stage ...
PDE4 is the predominant PDE family that controls cAMP and LTCC in rodent cardiomyocytes. In the present study, we show that Pde4a, Pde4b, and Pde4d are expressed in mouse heart, but only PDE4B and PDE4D are associated with CaV1.2 channels. Whereas β-AR stimulation of ICa,L is normal in Pde4a-/- and Pde4d-/- myocytes, the β-AR responses of ICa,L, Ca2+ transients, and contraction are enhanced in myocytes from Pde4b-/- mice, and this is accompanied by an increased propensity for arrhythmia. β-AR stimulation of Ca2+ transients and contraction are also enhanced in myocytes from Pde4d-/- mice independently of ICa,L. For the first time to our knowledge, our results identify PDE4B as a major regulator of ICa,L and cardiac function and suggest that PDE4B and PDE4D regulate ECC by different mechanisms. In mouse ventricular myocytes, pharmacological inhibition of PDE4 does not affect basal ICa,L but strongly enhances the effect of β-AR stimulation (Figure 1). A similar regulation of ICa,L by PDE4 was ...
Sigma-Aldrich offers abstracts and full-text articles by [F Hubert, M Belacel-Ouari, B Manoury, K Zhai, V Domergue-Dupont, P Mateo, F Joubert, R Fischmeister, V Leblais].
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After reviewing the MRI and spinal tap from U of I, he confirmed the diagnosis of PDE (that the right side of the brain and its lining was inflamed and being attacked by her own immune system), but quickly snapped us out of our funk. He didnt down play the seriousness of the situation, but said that he had successfully treated PDE before and he has no reason to think it couldnt happen again. He warned us that we would likely have to test different combinations and dosages and there were no guarantees that the drug regimen would work for Payton. However, there was no reason to give up just yet; we should still have some hope. We stayed in Chicago the rest of the week while Dr. Podell developed the treatment, and each day we saw our little girl come back a little at a time. By the end of the week, he was confident she was stable enough to go home ...
After reviewing the MRI and spinal tap from U of I, he confirmed the diagnosis of PDE (that the right side of the brain and its lining was inflamed and being attacked by her own immune system), but quickly snapped us out of our funk. He didnt down play the seriousness of the situation, but said that he had successfully treated PDE before and he has no reason to think it couldnt happen again. He warned us that we would likely have to test different combinations and dosages and there were no guarantees that the drug regimen would work for Payton. However, there was no reason to give up just yet; we should still have some hope. We stayed in Chicago the rest of the week while Dr. Podell developed the treatment, and each day we saw our little girl come back a little at a time. By the end of the week, he was confident she was stable enough to go home ...
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General Research Interests: Regulation and function of cyclic nucleotide phosphodiesterases in the cardiovascular system. Second messenger cyclic nucleotides (cAMP and cGMP) regulate many signaling pathways in the cardiovascular system. For example, the vascular tone, smooth muscle cell growth, and cardiac muscle contractility are all regulated by cyclic nucleotide signaling. We are interested in phosphodiesterases (PDEs), the enzymes that break down cyclic nucleotides and thus control the amplitude, duration, and compartmentalization of cyclic nucleotide signaling in the cell. It has become increasingly clear that cyclic nucleotide degradation by PDEs is not a constitutive function of the cell, but rather a highly regulated one controlled by different mechanisms in different physiological and pathological circumstances. PDE regulation and function is further complicated by the fact that there are more than 50 individual PDEs belonging to 11 different PDE families, yet our understanding of the ...
General Research Interests: Regulation and function of cyclic nucleotide phosphodiesterases in the cardiovascular system. Second messenger cyclic nucleotides (cAMP and cGMP) regulate many signaling pathways in the cardiovascular system. For example, the vascular tone, smooth muscle cell growth, and cardiac muscle contractility are all regulated by cyclic nucleotide signaling. We are interested in phosphodiesterases (PDEs), the enzymes that break down cyclic nucleotides and thus control the amplitude, duration, and compartmentalization of cyclic nucleotide signaling in the cell. It has become increasingly clear that cyclic nucleotide degradation by PDEs is not a constitutive function of the cell, but rather a highly regulated one controlled by different mechanisms in different physiological and pathological circumstances. PDE regulation and function is further complicated by the fact that there are more than 50 individual PDEs belonging to 11 different PDE families, yet our understanding of the ...
cAMP-specific 3,5-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the PDE4A gene. The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the secondary messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Recently, it has been shown through the use of PDE4A knock out mice that PDE4A may play a role in the regulation of anxiety and emotional memory. PDE4A is a target of a number of drugs including: rolipram (antidepressant and antiinflammatory) and cilomilast (antiinflammatory) - inhibits PDE4A isoforms 1, 2, 6, and 7 roflumilast (antiinflammatory) - inhibits PDE4A isoforms 1, 2, and 6 GRCh38: Ensembl release 89: ENSG00000065989 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000032177 - Ensembl, May ...
In mammals, adenosine 3, 5-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. It is known to act through protein phosphorylation via PRKA and through the activation of guanine nucleotide exchange factors like EPAC. Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-containing adenylyl cyclases are also present, and on the activity of cyclic nucleotide phosphodiesterases (PDE) whose role is to degrade cAMP into 5-AMP. The PDE superfamily is subdivided into 11 families (PDE1 to 11), which act on either cAMP or cGMP, or on both cAMP and cGMP although with different enzymatic properties. PDE10, which is more effective on cAMP than cGMP, has been known for almost 15 years and is mostly studied in the brain where it is associated with neurological disorders. Although a high level of PDE10A gene expression is observed in the testis, information on the identity of the isoforms or ...
Cyclic AMP (cAMP) or cyclic adenosine monophosphate acts as a secondary messenger and is used in cell signalling. The concentration of cAMP in cytosol can be increased via an extracellular signal. It can be deactivated by phosphodiesterase (PDE) into AMP. In most animal cells, cAMP can activate protein kinase A (PKA) by binding to its regulatory subunits which activates and release its active catalytic subunits. These active catalytic subunits can then go on to phosphorylate other proteins, creating a signalling cascade[1]. In unstimulated cells, levels of cAMP are kept low by phosphodiesterases in order to keep the bound inactive[2]. ATP is converted to cAMP by adenylyl cyclase, cAMP is then used in a range of signalling pathways. ...
The PDE3 enzymes or low Kin cGMP-inhibited phosphodiesterases have long been established as important mediators of cellular physiology, and synthetic PDE3 inhibitors have been critical to the delineation of the enzymes roles. Yet despite decades of progress on the biology of these enzymes, the medicinal chemistry landscape relating to PDE3 inhibitors has remained essentially unchanged since the mid 1990s. Up until then the field was at the cutting edge of drug design; without the tools of molecular and structural biology, molecules of high potency were being achieved using logical pharmacophore models and lead modification. Yet virtually all the impetus went out of this area on the back of failures at the clinic and PDE3 as a therapeutic target largely fell out of favour. A decade later and with the new technologies of structural and molecular biology breathing new life into PDE3 research in general, PDE3 inhibitors are sought for target validation in an array of therapeutic applications. ...
Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively. Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
PF-2545920 a highly selective and potent PDE10A inhibitor with an IC50 of 0.37 nM. Find all the information about PF-2545920 for cell signaling research.
Complete information for PDE6B gene (Protein Coding), Phosphodiesterase 6B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793-812. doi ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ... Horton YM, Sullivan M, Houslay MD (Jun 1995). "Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic ...
... cyclic nucleotide phosphodiesterases ARF1 (ADP Ribosylation factor 1) A type (Kv4.3; Shal-related subfamily, member 3) voltage- ... The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the ... type III phosphatidylinositol 4-kinase β) IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment ... 27 (4): 203-9. doi:10.1016/j.tins.2004.01.010. PMID 15046879. S2CID 24156457. Dason JS, Romero-Pozuelo J, Marin L, Iyengar BG, ...
September 2003). "Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system ... PDE3A can be either membrane-associated or cytosolic, depending on the variant and the cell type it is expressed in. PDE3A and ... Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... WO 03012030, Movsesian M, "Isoform-Selective Inhibitors and Activators of PDE3 Cyclic Nucleotide Phosphodiesterases", published ...
"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor". British Journal of ... A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action ... Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998). "Rolipram, a type IV-specific phosphodiesterase inhibitor, ... Dinter, H (February 2000). "Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?". BioDrugs. ...
Cyclic-nucleotide 3'-phosphodiesterase, a myelin-associated enzyme that makes up 4% of total CNS myelin protein Chronic ... nonbacterial prostatitis, a pelvic pain condition affecting men c-type Natriuretic Peptide, a vasoactive hormone Certified ...
"Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... Fertel R, Weiss B (July 1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" ( ... cGMP-specific phosphodiesterase type 5 is an enzyme (EC 3.1.4.17) from the phosphodiesterase class. It is found in various ... Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ...
He is best known for his work with cyclic nucleotide phosphodiesterases. He was the first to propose, based on his experimental ... He showed that a single cell type may contain more than one form of phosphodiesterase [6,7] and that different forms of ... one on the potential therapeutic application of cyclic nucleotides: (Weiss, Benjamin, ed., Cyclic Nucleotides in Disease[1]), ... Cyclic Nucleotide Phosphodiesterases: Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated ...
This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. ... "cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line". Biochemical ... This protein functions in the cellular export of its substrate, cyclic nucleotides. ... a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and ...
Cyclic-nucleotide 3'-phosphodiesterase. Moreover, oligodendrocytes also developed and migrated into fiber bundles in mice when ... Using doses between 1 μM to 3 μM of RA can generate neurons as the most abundant cell type. Neurons under this treatment ... The cell line is pluripotent and can differentiate into cell types of all three germ layers. Also, it is the most characterized ... At concentration of 0.5-1% DMSO induced P19 cells to aggregate and process mesodermal and endodermal cell types. The cellular ...
... is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. ... The effect of bucladesine as a cAMP analog has been studied on the pentylenetetrazol-induced seizure in the wild-type mice. The ... Bucladesine (50-100nM/mouse) showed significant attenuation in the morphine withdrawal syndrome in the wild-type mice. In ... 28 (4): 445-54. doi:10.1111/fcp.12045. PMID 24033391. Bucladesine at the US National Library of Medicine Medical Subject ...
It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine ... "The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I ... Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5'-pApA (phosphadenylyl adenosine). pApA is also ... "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9 ...
"Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... Journal of Cyclic Nucleotide Research. 2 (3): 139-48. PMID 6493. Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless ... "Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded ...
1998). "Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: ... "Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential ... High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene. The ... "Entrez Gene: PDE9A phosphodiesterase 9A". Verhoest PR, Fonseca KR, Hou X, et al. (2012). "Design and discovery of 6-[(3S,4S)-4- ...
2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi:10.1067/mai ... Jan 2012). "Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental ... Fertel R, Weiss B (1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". Mol. ... Weiss B (1975). "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv. ...
Cyclic nucleotides can be found in many different types of eukaryotic cells, including photo-receptor rods and cones, smooth ... cAMP's role in this process terminates upon hydrolysis to AMP by phosphodiesterase. Cyclic nucleotides are well-suited to act ... The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) and cyclic ... A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... Paraxanthine is a phosphodiesterase type 9 (PDE9) inhibitor and it is sold as a research molecule for this same purpose. ... Paraxanthine is a selective inhibitor of cGMP-preferring phosphodiesterase (PDE9) activity and is hypothesized to increase ... Paraxanthine is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits ...
Cyclic GMP possibly opens cyclic nucleotide-gated (CNG) K+-selective channels, thereby causing hyperpolarization of the ... Kong, N., Xu, X., Zhang, Y., Wang, Y., Hao, X., Zhao, Y., Qiao, J., Xia, G. and Zhang, M. (2017) Natriuretic peptide type C ... The cGMP signal is terminated by the hydrolysis of cGMP through phosphodiesterase (PDE) activity and inactivation of GC. On ... The consequential hyperpolarization activates hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. The ...
White matter Schwann cells 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase) List of human cell types derived from the germ ... Oligodendrocytes are a type of glial cell. They arise during development from oligodendrocyte precursor cells (OPCs), which can ... They are the last cell type to be generated in the CNS. Oligodendrocytes were discovered by Pío del Río Hortega. ... Oligodendrocytes (from Greek 'cells with a few branches'), or oligodendroglia, are a type of neuroglia whose main functions are ...
Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. CiteSeerX 10.1.1.319. ... Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell. cAMP-dependent pathway is ... Molecules that inhibit the cAMP pathway include: cAMP phosphodiesterase converts cAMP into AMP by breaking the phosphodiester ... Increases in concentration of the second messenger cAMP may lead to the activation of cyclic nucleotide-gated ion channels ...
Differential Activation and Inhibition of the Multiple Forms of Cyclic Nucleotide Phosphodiesterase. Advances in Cyclic ... A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug which works by blocking the degradative action of ... Fertel R, Weiss B (July 1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". ... Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ...
"Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... These proteins degrade the second messenger cAMP, which is a key signal transduction molecule in multiple cell types, including ... "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene. The PDE4D gene is ...
Cyclic GMP possibly opens cyclic nucleotide-gated (CNG) K+-selective channels, thereby causing hyperpolarization of the ... The cGMP signal is terminated by the hydrolysis of cGMP through phosphodiesterase (PDE) activity and inactivation of GC. On ... They include the chemokine CCL20, atrial natriuretic peptide (ANP), specific odorants, natriuretic peptide type C (NPPC), and ... The consequential hyperpolarization activates hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. The ...
Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv Cyclic Nucleotide Res ... http://www.garlandscience.com/textbooks/0815323042.asp?type=reviews. *Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of ... Fertel R, Weiss B (1976). „Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" (abstract). ... Weiss B, Hait WN (1977). „Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annu. Rev ...
Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... "Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality". Heart. 102 ( ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... McMahon, C. G.; McMahon, C. N.; Leow, L. J. & Winestock, C. G. (2006). "Efficacy of type-5 phosphodiesterase inhibitors in the ...
... resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of ... A third type of light-sensing cell, the photosensitive ganglion cell, is important for entrainment of circadian rhythms and ... This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, ... There are two types of centre-surround structures in the retina - on-centres and off-centres. On-centres have a positively ...
Cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the Immune system. GRCh38: Ensembl release 89: ENSG00000197971 ... In general, the major form of MBP is a protein of about 18.5 Kd (170 residues). In melanocytic cell types, MBP gene expression ... 48 (4): 713-21. doi:10.1016/0092-8674(87)90249-2. PMID 2434243. Kamholz J, Spielman R, Gogolin K, et al. (1987). "The human ... 40 (4): 365-73. PMC 1684086 . PMID 2437795. Roth HJ, Kronquist KE, Kerlero de Rosbo N, et al. (1987). "Evidence for the ...
Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... PDE1 (phosphodiesterase type 1) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase ... Kakkar R, Raju RV, Sharma RK (July 1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)". Cell. Mol. Life ... Dousa TP (January 1999). "Cyclic-3',5'-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney ...
... cAMP binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding ... cyclic monophosphate (8-Br-cAMP) Acrasin specific to chemotactic use in Dictyostelium discoideum. phosphodiesterase 4 (PDE 4) ... Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell. Still, there are some ... Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in ...
"Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling". ... Phosphodiesterase enzymes have been shown to be different in different types of cells, including normal and leukemic ... Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ...
"Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell.[9]. ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488-520. doi:10.1124/pr. ...
Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound ... One type of photosensitive pigment Three types of photosensitive pigment in humans ... Each transducin then activates the enzyme cGMP-specific phosphodiesterase (PDE).. *PDE then catalyzes the hydrolysis of cGMP to ... resulting in the closure of cyclic nucleotide-gated Na+ ion channels located in the photoreceptor outer segment membrane. ...
2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase). *List of human cell types derived from the germ layers ... Oligodendrocytes are a type of glial cell. They arise during development from oligodendrocyte precursor cells (OPCs),[7] which ... Oligodendrocytes (from Greek 'cells with a few branches'), or oligodendroglia, are a type of neuroglia whose main functions are ... Precursors and both mature types are typically identified by their expression of the transcription factor OLIG2.[10] ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... LIPE, AOMS4, FPLD6, HSL, LHS, lipase E, hormone sensitive type. External IDs. OMIM: 151750 MGI: 96790 HomoloGene: 3912 ... which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs protein- ... 69 (3-4): 211-4. doi:10.1159/000133966. PMID 7698015.. *. Langin D, Laurell H, Holst LS, et al. (1993). "Gene organization and ...
Johner, A., Kunz, S., Linder, M., Shakur, Y. and Seebeck, T. (2006). "Cyclic nucleotide specific phosphodiesterases of ... http://www.garlandscience.com/textbooks/0815323042.asp?type=reviews. *Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ...
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.[5] ... type 1 angiotensin receptor binding. • protein complex binding. • signal transducer activity. • protein binding. • GTPase ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... retina development in camera-type eye. • Ras protein signal transduction. • cell proliferation. • cellular response to hypoxia ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... The third type of glucose 6-phosphatase deficiency, glucose 6-phosphatase-β deficiency, is characterized by a congenital ... 1993). "Glycogen Storage Disease Type I". PMID 20301489.. Cite journal requires ,journal=. (help). ... Chou JY, Matern D, Mansfield BC, Chen YT (March 2002). "Type I glycogen storage diseases: disorders of the glucose-6- ...
3 Types of G protein signaling *3.1 Heterotrimeric G proteins *3.1.1 Common mechanism *3.1.1.1 Activation ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ...
... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... guanyl-nucleotide exchange factor activity. • RNA binding. Cellular component. • cytoplasm. • ciliary basal body. • centrosome ... "Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: paucity of mutations in the coding ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... It is suggested that 57 enzymes fall into the type I category whereas the rest fall into the type II group, including the ... and there are two classifications of these enzymes including type I and type II. ... Other types of PET degrading hydrolases have been known before this discovery.[2] These include hydrolases such as: lipases, ...
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was ... Involved in growth and metastasis of some types of tumors.[24]. *Used in the endocrine system for peptide and amino-acid ... When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide ... These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates ...
Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ... Types[edit]. There are membrane-bound (type 1, guanylate cyclase-coupled receptor) and soluble (type 2, soluble guanylate ... Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on ... Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the ...
Yeast tRNA cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3' end. Yeast tRNA ... exon then performs a nucleophilic attack at the first nucleotide following the last nucleotide of the intron at the 3' splice ... This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts for more than 99% of splicing. ... Splicing occurs in all the kingdoms or domains of life, however, the extent and types of splicing can be very different between ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ...
This compound is a potent inhibitor of cGMP specific phosphodiesterase type 5, the enzyme that degrades the signalling molecule ... This block of nucleotide biosynthesis is more toxic to rapidly growing cells than non-dividing cells, since a rapidly growing ... cyclic guanosine monophosphate.[40] This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results from an ...
The cyclic AMP-regulatory dimers are degraded by phosphodiesterase and release 5'AMP. DNA in the cell nucleus binds to ... G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • activation of adenylate cyclase ... LHCGR have been found in many types of extragonadal tissues, and the physiologic role of some has remained largely unexplored. ... Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was ...
Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3 ... This α-subunit then activates a phosphodiesterase that catalyzes the conversion of cGMP to GMP, thereby reducing current ... though in some cases the truncated proteins may be able to coassemble with wild-type channels in a dominant negative fashion. ... There are at least four genetic causes of congenital ACHM, two of which involve cyclic nucleotide-gated ion channels (ACHM2/ ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Phosphodiesterase type 11 (PDE11) is a type of phosphodiesterase enzyme. An inhibitor is BC11-38. ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... "Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth ... For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to ... 379 (6565): 560-4. doi:10.1038/379560a0. PMID 8596638.. *^ Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... 1994). "New type of linkage between a carbohydrate and a protein: C-glycosylation of a specific tryptophan residue in human ... 260 (4): 540-52. doi:10.1006/jmbi.1996.0420. PMID 8759319.. *. Krieg J, Hartmann S, Vicentini A, et al. (1998). "Recognition ...
... acts as a phosphodiesterase (PDE) type-1 inhibitor in isolated rabbit aorta,[12] Independent of vinpocetine's ... Hagiwara M, Endo T, Hidaka H (February 1984). "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle ... O=C(OCC)C=4n1c3c(c2ccccc12)CCN5[[email protected]]3[[email protected]](C=4)(CCC5)CC ... 26-4-2/h5-6,8-9,14,20H,3-4,7,10-13H2,1-2H3/t20-,22+/m1/s1 Y ... Glu release after in vivo exposure to 4-aminopyridine (4-AP) which suggests an important mechanism for vinpocetine ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... 62 (Pt 4): 299-305. doi:10.1046/j.1469-1809.1998.6240299.x. PMID 9924608.. ...
Single-nucleotide polymorphisms (SNPs) in the P2RX7 receptor gene are associated with an increased risk of bone fracture. The ... There are two types of NTs: Concentrative nucleoside transporters (CNTs): Na+-dependent symporters Equilibrative nucleoside ... the ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and alkaline phosphatases (APs). Extracellular AMP is hydrolyzed ... for sustained platelet aggregation through the inhibition of adenylate cyclase and a corresponding decrease in cyclic adenosine ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Type II[edit]. Type II site-specific deoxyribonuclease. Structure of the homodimeric restriction enzyme EcoRI (cyan and green ... Type V[edit]. Type V restriction enzymes (e.g., the cas9-gRNA complex from CRISPRs[43]) utilize guide RNAs to target specific ... Type l[edit]. Type I restriction enzymes were the first to be identified and were first identified in two different strains (K- ...
... act by increasing intracellular concentrations of cyclic AMP, which has a broad range of anti-inflammatory effects on various ... 3,5-Cyclic-AMP Phosphodiesterases * Cyclic Nucleotide Phosphodiesterases, Type 3 * Cyclic Nucleotide Phosphodiesterases, Type ... Inhibitors of phosphodiesterase type 4 (PDE4) act by increasing intracellular concentrations of cyclic AMP, which has a broad ... Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease Lancet. 2005 Jan 8-14;365(9454):167-75. doi ...
... which are in part mediated by their inhibition of phosphodiesterase (PDE). A mem … ... Cyclic AMP / metabolism * Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism * Glioblastoma / drug therapy* ... the most common type of brain tumor. The purpose of this study was to determine whether theobromine could exert growth ... which are in part mediated by their inhibition of phosphodiesterase (PDE). A member of the PDE family, PDE4, is widely ...
3,5-Cyclic-AMP Phosphodiesterases [D08.811.277.352.640.150]. *Cyclic Nucleotide Phosphodiesterases, Type 5 [D08.811.277.352. ... 3,5-Cyclic-GMP Phosphodiesterases [D08.811.277.352.640.155]. *Cyclic Nucleotide Phosphodiesterases, Type 5 [D08.811.277.352. ... "Cyclic Nucleotide Phosphodiesterases, Type 5" by people in Harvard Catalyst Profiles by year, and whether "Cyclic Nucleotide ... "Cyclic Nucleotide Phosphodiesterases, Type 5" by people in Profiles.. * Are Phosphodiesterase-5 Inhibitors a New Frontier for ...
Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of ... Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of ... Kakkar, R., Raju, R. V. S., and Sharma, R. K. (1999). Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1). Cell. ... Beavo, J. A. (1995). Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol. Rev. 75, 725- ...
"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor". British Journal of ... A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action ... Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998). "Rolipram, a type IV-specific phosphodiesterase inhibitor, ... Dinter, H (February 2000). "Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?". BioDrugs. ...
FrancisSH, Wolfe L, and Corbin JD (1991) Purification of type I alpha and type I beta isozymes and proteolyzed type I beta ... Cyclic nucleotide phosphodiesterase superfamily, in Cyclic Nucleotide Phosphodiesterases in Health and Disease (Beavo J, ... Cyclic GMP-binding cyclic GMP-specific phosphodiesterase from lung, in Cyclic Nucleotide Phosphodiesterases: Structure, ... and inhibitor selectivity of cyclic nucleotide phosphodiesterases, in Cyclic Nucleotide Phosphodiesterases in Health and ...
Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias.. Molina CE, Leroy J, Richter W, ... Database of Single Nucleotide Polymorphisms (dbSNP). *SNP Submission Tool. *All Variation Resources... ... Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular ... The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases ( ...
Mouse monoclonal antibodies against 2′,3′-cyclic nucleotide phosphodiesterase (CNPase) (1:800; Covance), myelin basic protein ( ... Multiple cell types have been grafted into the demyelinated spinal cord and remyelinate the demyelinated axons to varying ... Multiple types of cells, including NSCs, glial-restricted precursors (GRPs), and OPCs, have been transplanted into the injured ... The cells were incubated on an anti-RAN-2 antibody-coated dish for 30 min to deplete type 1 astrocytes and meningeal cells and ...
... type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative colitis via down-regulation of iNOS and ... Advances in targeting cyclic nucleotide phosphodiesterases. Maurice, D.H.; Ke, H.; Ahmad, F. ... A short review on structure and role of cyclic-3′,5′-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool ... Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative... El-Ashmawy, Nahla E.; Khedr ...
Type 4 Cyclic Nucleotide PhosphodiesterasesIBA 05/2012. 1. OxygenIBA 01/2012. ...
Cyclic Nucleotide Phosphodiesterases, Type 4/genetics*; Genetic Predisposition to Disease*; Genetics, Population; Genome-Wide ... The phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) gene (PDE4D) is a regulator of airway ...
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793-812. doi ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ... Horton YM, Sullivan M, Houslay MD (Jun 1995). "Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic ...
... by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). Type 4 PDE (PDE4) is selective to cAMP in ... Andersen PH, Klysner R, Geisler A. Cyclic AMP phosphodiesterase activity in rat brain following chronic treatment with lithium ... Antidepressant Effects on cAMP Specific Phosphodiesterase (PDE4) in Depressed Patients. The safety and scientific validity of ... Conti M, Nemoz G, Sette C, Vicini E. Recent progress in understanding the hormonal regulation of phosphodiesterases. Endocr Rev ...
Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006;58(3):488-520. ... Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4. J Pharm Pharmacol. 2004;56( ... Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014;13(4):290-314. ... 3 The therapeutic utility of controlling the intracellular levels of cyclic-AMP, and of cyclic guanosine monophosphate (cyclic- ...
type. Contribution to journal publication status. published. subject. *Endocrinology and Diabetes. keywords. human lymphocytes ... Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune ... Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune ... Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes. Ekholm, Dag ...
Cyclic Nucleotide Phosphodiesterases, Type 6). ... is the most common and lethal type of neoplasms in the central ... we subjected pde6c and wild-type (WT) retinas at 5 dpf/ 120 h postfertilization (hpf) to RNA sequencing (RNA-Seq) on the ... In conclusion, 4 genes (ORM1, ORM2, PLG, and AOX1) with immune response and the complement and coagulation cascades pathway may ... 0 (Zebrafish Proteins); EC 3.1.4.- (Pde6c protein, zebrafish); EC 3.1.4.35 ( ...
The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases ( ...
Combinatorial biosynthesis of 5/5/6 type polycyclic tetramate macrolactams (PoTeMs) was achieved in an engineered ikarugamycin ... Cyclic Nucleotide Phosphodiesterases, Type 1. A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily ... Although the type 1 enzymes are classified as 3,5-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class ... type II (intermediate form), and type III (Kugelberg-Welander disease). Type I is fatal in infancy, type II has a late ...
A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in ... A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in ...
Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic ... Treatment with the type IV phosphodiesterase inhibitor Ro 20-1724 protects renal and mesenteric blood flow in endotoxemic rats ... Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic ... Cyclic AMP-mediated regulation of vascular smooth muscle cell cyclic AMP phosphodiesterase activity. Rose, R.J., Liu, H., ...
Cyclic Nucleotide Phosphodiesterases, Type 4. *Endothelium, Vascular/cytology/drug effects. *Female. *Humans ...
Emesis induced by inhibitors of type IV cyclic nucleotide phosphodiesterase (PDE IV) in the ferret. Neuropharmacology 1999. 38: ... Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 2001. 108:671-680. View this article via: PubMed CrossRef Google ... The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 2000. 63:1-38. ... Cyclic nucleotides cAMP and cGMP are degraded by at least 11 families of phosphodiesterases (PDEs 1-11) classified according to ...
De Angelis D. A. and Braun P. E. (1994) Isoprenylation of brain 2′,3′-cyclic nucleotide 3′-phosphodiesterase modulates cell ... ONeill R. C. and Braun P. E. (2000) Selective synthesis of 2′,3′-cyclic nucleotide 3′-phosphodiesterase isoform 2 and ... cyclic nucleotide 3′-phosphodiesterase (CNP), myelin/OL basic protein and the tight junction protein claudin-11 (formerly ... Other cell types have also been found to have several different microdomains of different composition (Madore et al. 1999; ...
... of Eotaxin-Mediated Human Eosinophil Activation and Migration by the Selective Cyclic Nucleotide Phosphodiesterase Type 4 ... Patent type. Prior art keywords. cells. leukocytes. sample. method. erythrocytes. Prior art date. 2011-11-25. Legal status (The ... Methods for enriching specific cell-types by density gradient centrifugation US5514340A (en) 1996-05-07. Device for separating ... Methods for enriching specific cell-types by density gradient centrifugation US5474687A (en) 1994-08-31. 1995-12-12. Activated ...
Phosphodiesterases listed: PDE, PLC, PLD. [1] Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases ... They are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Roughly, the sub-types can ... No less than eleven sub-types of the enzyme family of phosphodiesterases (PDE; EC 3.1.4.-) are known to date, many of which ... 2] Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug ...
1999) Emesis induced by inhibitors of type IV cyclic nucleotide phosphodiesterase (PDE IV) in the ferret. Neuropharmacology 38: ... 2011) Disease-modifying effect of ASP3258, a novel phosphodiesterase type 4 inhibitor, on subchronic cigarette smoke exposure- ... 1996) Biarylcarboxylic acids and -amides: inhibition of phosphodiesterase type IV versus [3H]rolipram binding activity and ... 2000) Phosphodiesterase 4 inhibitors and the treatment of asthma: where are we now and where do we go from here? Drugs 59:193- ...
Oral administration of an FDA- approved type 5 cyclic nucleotide-specific phosphodiesterase inhibitor (PDE5i; tadalafil) to the ... Cyclic nucleotide phosphodiesterases (PDEs), the enzymes that degrade and inactivate cAMP, play a critical role in the ... This harmful heme has the ability to destroy the structure and function of several types of cells in the body. Therefore, in ... Regulation of phosphodiesterases and cAMP signaling during the host-pathogen interaction in the pulmonary endothelium ...
Of the 11 families of phosphodiesterases found in the human genome, three decades of pharmacological data have clearly ... Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu ... Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. J Am Coll Cardiol 59(24):2182-2190 ... Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC (2014) Advances in targeting cyclic nucleotide phosphodiesterases. ...
108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 5 * 101700083883 UBA2 Proteins 0.000 ... 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 13 * UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate ... 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 5 * ... 201000005787 hematologic cancer Diseases 0.000 claims 4 * 201000009596 autoimmune hypersensitivity disease Diseases 0.000 ...
Cyclic Nucleotide Phosphodiesterases, Type 4; K676NL63N7 / Rolipram ... Semantic-Type. And with semantic types: A. Entity. A1. Physical Object. A1.1. Organism. A1.1.1. Archaeon. A1.1.2. Bacterium. ... Publication-Type. And with publication types: Clinical Trial. Editorial. Letter. Meta-Analysis. Practice Guideline. Randomized ... include both record types include both record types but rank higher the records having abstract (the default BML behavior) + ...
  • Inhibitors of phosphodiesterase type 4 (PDE4) act by increasing intracellular concentrations of cyclic AMP, which has a broad range of anti-inflammatory effects on various key effector cells involved in asthma and chronic obstructive pulmonary disease (COPD). (nih.gov)
  • Ultimately, clinicians will want to know whether PDE4 inhibitors are anything more than expensive "designer" theophylline, the archetypal non-selective phosphodiesterase inhibitor. (nih.gov)
  • Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of neuronal plasticity-related genes, neurotrophic factors, and neuroprotective molecules. (frontiersin.org)
  • Are Phosphodiesterase-5 Inhibitors a New Frontier for Prevention of Colorectal Cancer? (harvard.edu)
  • Poor understanding of the topography of cyclic nucleotide (CN) phosphodiesterase (PDE) catalytic sites compromises development of potent, selective inhibitors for therapeutic use. (aspetjournals.org)
  • Rodent studies have consistently shown upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP) system induced by different types of chronic but not acute antidepressant treatment including serotonin and norepinephrine uptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, lithium and electroconvulsions. (clinicaltrials.gov)
  • 2 , 3 The therapeutic utility of controlling the intracellular levels of cyclic-AMP, and of cyclic guanosine monophosphate (cyclic-GMP), with PDE inhibitors is well established. (bloodjournal.org)
  • 4 These agents are in clinical testing or have been US Food and Drug Administration (FDA)-approved for the treatment of multiple conditions, from cardiac failure to fertility, from neurodegeneration to inflammatory/autoimmunity conditions and erectile dysfunction (see Maurice et al 4 for a comprehensive review on PDE inhibitors). (bloodjournal.org)
  • The phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) gene (PDE4D) is a regulator of airway smooth-muscle contractility, and PDE4 inhibitors have been developed as medications for asthma. (nih.gov)
  • The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. (bvsalud.org)
  • These data suggest that phosphodiesterase type 5 inhibitors may have effects that distinguish them from other treatments for pulmonary hypertension and merit further study. (ersjournals.com)
  • Recent studies showed evidence that phosphodiesterase (PDE)4-inhibitors stabilized endothelial cells. (unboundmedicine.com)
  • Barnette MS, Underwood DC (2000) New phosphodiesterase inhibitors as therapeutics for the treatment of chronic lung disease. (springer.com)
  • Sub-efficacious doses of phosphodiesterase 4 and 5 inhibitors improve memory in a mouse model of Alzheimer's disease. (bioportfolio.com)
  • Increasing their levels by phosphodiesterase inhibitors (PDE-Is) enhanced cognitive functions and rescued mem. (bioportfolio.com)
  • Phosphodiesterase (PDE)4 inhibitors, by preventing the breakdown of cAMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. (unboundmedicine.com)
  • 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. (strath.ac.uk)
  • It also belongs to another family of drugs called phosphodiesterase type 4, or PDE4, inhibitors. (joggingclubsablais.com)
  • The effects of β 2-adrenergic agonists, which stimulate cAMP synthesis, and phosphodiesterase inhibitors, which inhibit cAMP degradation, on acute lung injury are reviewed, and the relative advantages. (joggingclubsablais.com)
  • Background: Phosphodiesterase 4 (PDE4) inhibitors negatively modulate many inflammatory responses, and some of these pharmacological effects are mediated by inhibition of PDE4B in inflammatory cells. (thefreelibrary.com)
  • sup][5] By increasing intracellular cAMP level, phosphodiesterase 4 (PDE4) inhibitors are being developed as anti-inflammatory agents for the treatment of chronic inflammatory disorders such as asthma, chronic obstructive pulmonary disease, and psoriasis. (thefreelibrary.com)
  • In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or N(G)-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. (tudelft.nl)
  • Inhibitors of phosphodiesterase IV (PDE IV) increase acid secretion in rabbit isolated gastric glands: correlation between function and interaction with a high-affinity rolipram. (naver.com)
  • The article from Oliver et al 2 published in this issue of Hypertension represents the first study performed with an accurate experimental design and methodology demonstrating that inhibitors of isoform 5 of phosphodiesterase (PDE) might be potentially used as a new drug class for the treatment of essential hypertension. (ahajournals.org)
  • Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice. (naver.com)
  • Our earliest understanding of phosphodiesterase (PDE) inhibitors began with a series of publications by Sutherland and Rall in the 1950s, describing the properties of cyclic adenosine monophosphate (cAMP). (beds.ac.uk)
  • By the 1960s, the role of cyclic nucleotide second messengers, such as cAMP, in cell signaling and homeostasis was established, and regulation of this pathway by PDE inhibitors arose as a field of considerable interest. (beds.ac.uk)
  • A member of the PDE family, PDE4, is widely expressed in and promotes the growth of glioblastoma, the most common type of brain tumor. (nih.gov)
  • El-Adawy, Samar A. 2018-03-01 00:00:00 BackgroundRoflumilast (Rof), a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be an effective agent in inflammatory diseases and marketed for chronic obstructive pulmonary disease. (deepdyve.com)
  • Type 4 PDE (PDE4) is selective to cAMP in the brain. (clinicaltrials.gov)
  • Among components of the cAMP pathway, PDE4 appears to be critical for antidepressant effects because an inhibitor of PDE4, 4-[3-(cyclopenotoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram), showed antidepressant effects both in animals and humans, and various forms of antidepressant treatment induced increase in PDE4 in rodents. (clinicaltrials.gov)
  • Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3′,5′-cyclic adenosine monophosphate in lymphocytes. (bloodjournal.org)
  • Here, we review a decade-long exploration of the contribution of cyclic-AMP and PDE4 to the pathogenesis of B-cell lymphoma, 5 ⇓ ⇓ ⇓ - 9 culminating with the first-in-cancer clinical trial of a PDE4 inhibitor in advanced B-cell malignancies. (bloodjournal.org)
  • 6 Mechanistically, PDE4 inhibition resulted in elevation of intracellular cyclic-AMP levels and suppression of PI3K and AKT activity. (bloodjournal.org)
  • 6 These data linked the cyclic-AMP/PDE4 axis to the essential tonic BCR signals, highlighting the potential impact of PDE4 modulation in malignant B cells ( Figure 1 ). (bloodjournal.org)
  • Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia. (nih.gov)
  • A combination of pharmacological and genetic approaches was used to determine the role of type 4 cAMP-specific cyclic nucleotide phosphodiesterase 4 (PDE4) in reversing α 2 -adrenoceptor-mediated anesthesia, a behavioral correlate of emesis in non-vomiting species. (jci.org)
  • Baillie GS, Sood A, McPhee I, Gall I, Perry SJ, Lefkowitz RJ, Houslay MD (2003) Beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. (springer.com)
  • A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). (wikipedia.org)
  • It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor, depending on the dose. (wikipedia.org)
  • PDE4 hydrolyzes cyclic adenosine monophosphate (cAMP) to inactive adenosine monophosphate (AMP). (wikipedia.org)
  • The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. (wikipedia.org)
  • We also found that the inhibitory effect of stress on mossy fiber LTP was obviated by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3,-dipropylxanthine, the non-specific phosphodiesterase (PDE) inhibitor 3-isobutyl-methylxanthine, and the specific PDE4 inhibitor 4-(3-butoxy-4-methoxyphenyl)methyl-2-imidazolidone. (elsevier.com)
  • We compared for the first time the therapeutic potential of a specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary allergen exposure of previously sensitized and challenged mice. (elsevier.com)
  • Baillie GS, MacKenzie SJ, McPhee I, Houslay MD (2000) Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases. (springer.com)
  • Otezla-the generic name is apremilast-also exploited a new mechanism of action as the first inhibitor of phosphodiesterase 4 (PDE4) that results in increased expression of both anti-inflammatory proteins and reduced expression of their pro-inflammatory counterparts. (readbyqxmd.com)
  • Apremilast (Otezla®) is an orally administered, small molecule inhibitor of phosphodiesterase 4 (PDE4). (readbyqxmd.com)
  • Disruption of the cyclic AMP phosphodiesterase-4 (PDE4)-HSP20 complex attenuates the β-agonist induced hypertrophic response in cardiac myocytes. (ox.ac.uk)
  • Here, we report that inhibition of cAMP phosphodiesterase-4 (PDE4) induces the phosphorylation of HSP20 in resting cardiac myocytes and augments its phosphorylation by PKA following β-adrenergic stimulation. (ox.ac.uk)
  • 3. The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC(50) 1 - 5 microM), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. (strath.ac.uk)
  • as the predominant negative modulator of cyclic AMP signaling within microglia, phosphodiesterase 4 (PDE4) represents a promising target for modulating immune function. (elsevier.com)
  • Researchers found that levels of cAMP can be elevated by disrupting the activation of an enzyme called phosphodiesterase-4 (PDE4). (joggingclubsablais.com)
  • Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. (joggingclubsablais.com)
  • These drugs block the enzyme PDE4, which breaks down cyclic adenosine monophosphate, or cAMP. (joggingclubsablais.com)
  • The phosphodiesterase 4 (PDE4) family consists of four paralog. (joggingclubsablais.com)
  • Phosphodiesterase 4 (PDE4) is a major enzyme controlling the hydrolysis of cAMP in the brain. (ijbs.com)
  • IBMX is a broad-spectrum phosphodiesterase ( PDE ) inhibitor, with IC 50 s of 6.5, 26.3 and 31.7 μM for PDE3 , PDE4 and PDE5 , respectively. (medchemexpress.com)
  • Rolipram is a selective phosphodiesterases PDE4 inhibitor with IC 50 s of 3 nM, 130 nM and 240 nM for PDE4A, PDE4B, and PDE4D, respectively. (medchemexpress.com)
  • MR-L2 is a reversible and noncompetitive allosteric activator of long-isoform phosphodiesterase-4 (PDE4) , activates representative PDE4 long-isoform variants (PDE4A4, PDE4B1, PDE4C3, PDE4D5). (medchemexpress.com)
  • While inactivation of PDE4B, but not other PDE4 isotypes, is known to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-a) production in macrophages, a cell type critical in mediating innate immunity, the impact of PDE4B on many other inflammatory responses in these cells remains largely unknown. (thefreelibrary.com)
  • Short-term or long-term treatments with a phosphodiesterase-4 (PDE4) inhibitor result in opposing agonist-induced Ca 2+ responses in endothelial cells. (unistra.fr)
  • Some PDEs such as type 4 are specific for cAMP, while others such PDE5, specific for cGMP ( Beavo, 1995 ). (frontiersin.org)
  • cAMP is synthesized from adenosine 5-triphosphate (ATP) by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). (clinicaltrials.gov)
  • 1 The synthesis and degradation of cyclic-AMP are tightly controlled by 2 classes of enzymes, adenylyl cyclases and phosphodiesterases (PDEs), respectively. (bloodjournal.org)
  • Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune functions in lymphoid cells. (lu.se)
  • 8 These and other studies 9,10 also underlined the importance of cAMP phosphodiesterases (PDEs) for the spatiotemporal control of cAMP signals. (ahajournals.org)
  • It appears that for such events a supramolecular complex is required that comprises of the appropriate effector system together with signal termination enzymes such as PDEs and phosphatases that are sequestered by scaffolding proteins ( 4 ). (mcponline.org)
  • Functions of cyclic GMP include the regulation of cation channels and PDEs and activation of cyclic GMP-dependent protein kinase (PKG). (ersjournals.com)
  • PKG), cGMP-regulated phosphodiesterases (PDEs) and cyclic nucleotide-gated ion channels 4 . (ersjournals.com)
  • Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that are involved in the regulation of the intracellular second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) by controlling their rates of hydrolysis. (springer.com)
  • Cyclic nucleotide PDEs consist of 10 gene families, each having one or more isoforms. (aacrjournals.org)
  • The levels of this autocoid are a resultant of its rate of synthesis by adenylate cyclase and its rate of degradation by cAMP-phosphodiesterases (cAMP-PDEs). (joggingclubsablais.com)
  • Phosphodiesterases (PDEs) are a family of phosphohydrolyases that catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). (genecards.org)
  • Phosphodiesterases (PDEs) are the only route for degrading cAMP and are thus poised to regulate intracellular cAMP gradients. (ox.ac.uk)
  • Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the amplitude and duration of cAMP and cGMP signaling by controlling cyclic nucleotide (cNT) degradation. (pnas.org)
  • The second messenger 3′,5′-cyclic adenosine monophosphate (cyclic-AMP) uses effector proteins to influence cell function and fate. (bloodjournal.org)
  • Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. (nih.gov)
  • Heterologous GPCR stimuli have minimal to small effect on isoproterenol-induced β 2 AR activation and G-protein coupling for cyclic adenosine monophosphate (cAMP) production. (elsevier.com)
  • Elevation of the second messenger cyclic adenosine monophosphate (cAMP) in macrophages suppresses several inflammatory responses, including inflammatory mediator production and receptor-mediated phagocytosis. (thefreelibrary.com)
  • The human cyclic AMP-specific phosphodiesterase PDE-46 (HSPDE4A4B) expressed in transfected COS7 cells occurs as both particulate and cytosolic species that exhibit distinct kinetics of inhibition by the antidepressant rolipram" (PDF). (wikipedia.org)
  • Inhibition of human phosphodiesterase 4A expressed in yeast cell GL62 by theophylline, rolipram, and acetamide-45. (illumina.com)
  • Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998) Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. (springer.com)
  • The purpose of this study was to investigate the effect of rolipram , a phosphodiesterase-4 -specific inhibitor, in a segmental spinal nerve ligation model in rats . (bvsalud.org)
  • Phosphodiesterase-4 inhibitor ( rolipram ) and saline (vehicle) were administered intraperitoneally. (bvsalud.org)
  • This study suggests that the phosphodiesterase-4 inhibitor, rolipram , alleviates mechanical allodynia induced by segmental spinal nerve ligation in rats . (bvsalud.org)
  • Among the most important for pulmonary vascular homeostasis are factors that utilise cyclic guanosine monophosphate (cGMP) as an intracellular second messenger. (ersjournals.com)
  • In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. (ersjournals.com)
  • Two subtypes of natriuretic peptide receptor (NPR), NPR-A and NPR-B, are transmembrane guanylyl cyclases (particulate guanylyl cyclases), where the extracellular domain binds atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) or C-type natriuretic peptide and the intracellular domain hydrolyses guanosine triphosphate (GTP) to cGMP. (ersjournals.com)
  • PKG is the most important of these intracellular mediators, whereas the cGMP-regulated PDE type 5 (PDE5) is mainly responsible for modulating intracellular cGMP levels and PKG-dependent signalling produced by NO and natriuretic peptides 5 - 7 . (ersjournals.com)
  • Aizawa T, Wei H, Miano JM, Abe J, Berk BC, Yan C (2003) Role of phosphodiesterase 3 in NO/cGMP-mediated antiinflammatory effects in vascular smooth muscle cells. (springer.com)
  • Cyclic nucleotides cAMP and cGMP cooperate to ensure memory acquisition and consolidation. (bioportfolio.com)
  • SW480 colon tumor cells contain guanosine 3′,5′-monophosphate (cGMP) phosphodiesterase (PDE) isoforms of the PDE5 and PDE2 gene families that are inhibited by exisulind and new synthetic analogues. (aacrjournals.org)
  • Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also exhibits expression of a calcium-sensitive cAMP/cGMP phosphodiesterase 1C (PDE1C) and the vasopressin type 2 receptor. (forskningsdatabasen.dk)
  • NO induces cGMP production, which is a second-messenger molecule that exerts its effects through ion channels, protein kinases, and phosphodiesterases. (jneurosci.org)
  • Gene Ontology (GO) annotations related to this gene include 3',5'-cyclic-nucleotide phosphodiesterase activity and cGMP-inhibited cyclic-nucleotide phosphodiesterase activity . (genecards.org)
  • Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. (genecards.org)
  • The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. (medchemexpress.com)
  • 4 At the vascular level, because accumulation of cGMP can inhibit PDE 3, an isoform causing cAMP breakdown, 3 sildenafil could also act theoretically by increasing cAMP, the effector of the adenylyl cyclase-dependent relaxing pathway responsible for the vascular effects of several potent vasodilators, including isoproterenol, adenosine, papaverine, and dipyridamole 3 ( Figure ). (ahajournals.org)
  • In vascular smooth muscle cells, NO interacts with soluble guanylyl cyclase (sGC) to convert guanosine triphosphate (GTP) to cyclic GMP, which is hydrolysed and inactivated by phosphodiesterase type 5 (PDE5). (ersjournals.com)
  • In addition to these feedback mechanisms, there is the potential for gene regulation, as the promoter region of human PDE5 contains sites responsive to cyclic nucleotides 11 , 12 . (ersjournals.com)
  • Researchers at Saint Louis University School of Medicine have discovered a novel interaction between prostacyclin (PGI2) analogs and phosphodiesterase 5 (PDE5. (joggingclubsablais.com)
  • Sildenafil (UK-92480) is a potent phosphodiesterase type 5 ( PDE5 ) inhibitor with an IC 50 of 5.22 nM. (medchemexpress.com)
  • Steady-state activation of cardiac β-adrenergic receptors leads to an intracellular compartmentation of cAMP resulting from localized cyclic nucleotide phosphodiesterase (PDE) activity. (ahajournals.org)
  • Ahmed T, Frey JU (2005) Phosphodiesterase 4B (PDE4B) and cAMP-level regulation within different tissue fractions of rat hippocampal slices during long-term potentiation in vitro. (springer.com)
  • Ahmad F, Shen W, Vandeput F, Szabo-Fresnais N, Krall J, Degerman E, Goetz F, Klussmann E, Movsesian M, Manganiello V (2015) Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. (springer.com)
  • Cyclic AMP (cAMP) and its main effector Protein Kinase A (PKA) are critical for several aspects of neuronal function including synaptic plasticity.Simulations further demonstrate that generation of the cAMP microdomain requires a pool of PDE4D anchored in the cytosol and also requires PKA-mediated phosphorylation of PDE4D which increases its activity.The microdomain does not require impeded diffusion of cAMP, confirming that barriers are not required for microdomains. (nih.gov)
  • However, these GPCR stimuli significantly promote phosphorylation of phosphodiesterase 4D (PDE4D), and recruit PDE4D to the phosphorylated β 2 AR in a β-arrestin 2 dependent manner without promoting β 2 AR endocytosis. (elsevier.com)
  • Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. (ox.ac.uk)
  • We previously showed that methylxanthines, including caffeine and theophylline, have antitumor and antiinflammatory effects, which are in part mediated by their inhibition of phosphodiesterase (PDE). (nih.gov)
  • Oliver, Brian G. G. / Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle . (edu.au)
  • Phosphodiesterase are enzymes that catalyze the hydrolysis of the 3′ cyclic phosphate bonds of adenosine and/or guanosine 3′, 5′ cyclic monophosphate ( Beavo, 1995 ). (frontiersin.org)
  • 2. Calmodulin activated cyclic AMP or cyclic GMP PDE activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. (strath.ac.uk)
  • 2] Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. (axonmedchem.com)
  • Wang H, Gaur U, Xiao J, Xu B, Xu J, Zheng W. Targeting phosphodiesterase 4 as a potential therapeutic strategy for enhancing neuroplasticity following ischemic stroke. (ijbs.com)
  • 1] Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases: a diverse family of regulatory enzymes. (axonmedchem.com)
  • Phosphodiesterase 4B (PDE4B) has been evaluated as a genetic risk factor for schizophrenia. (cdc.gov)
  • Several other proteins such as cyclic nucleotide gated ion channels ( 1 ), phosphodiesterases (PDE) ( 2 ), and guanine nucleotide exchange factors (Epac) ( 3 ) bind cAMP. (mcponline.org)
  • Schematic diagram of the nitric oxide (NO)-cyclic guanosine monophosphate (GMP) signalling pathway. (ersjournals.com)
  • Bucladesine sodium salt (Dibutyryl-cAMP sodium salt) is a stabilized cyclic AMP (cAMP) analog and a selective PKA activator. (medchemexpress.com)
  • There are 11 human cyclic nucleotide phosphodiesterase (PDE) families. (aspetjournals.org)
  • In recent years, lysosomes have emerged as important signaling platforms that regulate cell metabolism, ion homeostasis, motility, and survival in response to the metabolic status of the cell ( 1-4 ). (aacrjournals.org)
  • cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the PDE4A gene. (wikipedia.org)
  • Prompted by significant changes in the expression of genes involved in Ca 2+ and cyclic AMP (cAMP) signaling pathways in CAD-resistant MCF7 breast cancer cells, we identified here an early lysosomal Ca 2+ release through P2X purinergic receptor 4 (P2RX4) and subsequent Ca 2+ - and adenylyl cyclase 1 (ADCY1)-dependent synthesis of cAMP as a signaling route mediating CAD-induced lysosomal membrane permeabilization and cell death. (aacrjournals.org)
  • Our data show that cotreatment of M. tuberculosis infected rabbits with the phosphodiesterase-4 inhibitor CC-3052 plus isoniazid significantly reduced the extent of immune pathogenesis, compared with antibiotic alone, as determined by histologic analysis of infected tissues and the expression of genes involved in inflammation, fibrosis, and wound healing in the lungs. (nih.gov)
  • The 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) is a highly abundant membrane-associated enzyme in the myelin sheath of the vertebrate nervous system. (jove.com)
  • of enzyme, phosphodiesterase 7B. (joggingclubsablais.com)
  • They found that copper binds to phosphodiesterase 3, or PDE3, an enzyme that binds to cAMP, halting cAMP's ability to facilitate the. (joggingclubsablais.com)
  • Phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. (medchemexpress.com)
  • Exisulind, the oxidative metabolite of sulindac, induces apoptosis and inhibits growth of tumor cell lines of diverse origins (3 , 4 , 5) , suggesting that an important survival pathway is modified by the drug. (aacrjournals.org)
  • Apremilast, an oral immunosuppressant that inhibits phosphodiesterase type 4, has been authorised in the European Union for use in these settings. (readbyqxmd.com)
  • W-7 hydrochloride inhibits the Ca 2+ -calmodulin -dependent phosphodiesterase and myosin light chain kinase with IC 50 values of 28 μM and 51 µM, respectively. (medchemexpress.com)
  • High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. (naver.com)
  • The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s). (nih.gov)
  • Type 4 cyclic nucleotide phosphodiesterases (PDE4s) are part of a superfamily of isoenzymes that hydrolyze and inactivate the second messenger cAMP. (joggingclubsablais.com)
  • Here, we provide evidence that type 4 cyclic nucleotide phosphodiesterases (PDE4s) are critical regulators of the cAMP/PKA-dependent activation of CFTR in primary human bronchial epithelial cells. (elsevier.com)
  • Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular arrhythmias in mice. (nih.gov)
  • In six families not related to each other they discovered different point mutations in the gene encoding phosphodiesterase. (joggingclubsablais.com)
  • The overall aim is to measure zinc signals and understand their function in the respective signal transduction pathways, and they were even able to identify molecular targets for zinc signals, such as cyclic nucleotide phosphodiesterases and protein tyrosine phosphatases. (uni-potsdam.de)
  • Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10" (PDF). (wikipedia.org)
  • Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected]" (PDF). (wikipedia.org)
  • Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. (springer.com)
  • For the cAMP assay, each tube containing 10 islets was incubated for 60 min in HKRB with 5.6 mM glucose containing 500 μM 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase, and the cAMP. (joggingclubsablais.com)
  • Importantly, pharmacologic and genetic means to increase cellular cAMP levels either by activating cAMP-inducing G-protein-coupled receptors (GPR3 or β 2 adrenergic receptor) or ADCY1, or by inhibiting cAMP-reducing guanine nucleotide-binding protein G(i) subunit α2, C-X-C motif chemokine receptor type 4, or cAMP phosphodiesterases, sensitized cancer cells to CADs. (aacrjournals.org)
  • Of the 11 families of phosphodiesterases found in the human genome, three decades of pharmacological data have clearly implicated PDE3 in cardiac function. (springer.com)
  • The extracellular receptor stimulated kinase ERK2 (p42(MAPK))-phosphorylated human cAMP-specific phosphodiesterase PDE4D3 at Ser579 and profoundly reduced ( approximately 75%) its activity. (hw.ac.uk)
  • Bucladesine sodium salt is also a phosphodiesterase (PDE) inhibitor. (medchemexpress.com)
  • Bucladesine is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. (wikipedia.org)
  • The effect of bucladesine as a cAMP analog has been studied on the pentylenetetrazol-induced seizure in the wild-type mice. (wikipedia.org)
  • Bucladesine (50-100nM/mouse) showed significant attenuation in the morphine withdrawal syndrome in the wild-type mice. (wikipedia.org)
  • Cyclic Nucleotide Phosphodiesterases, Type 5" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative. (deepdyve.com)
  • The classes of medication are bronchodilators including beta2-agonist, anticholinergics and anti-inflammatory drug including inhaled corticosteroid and phosphodiesterase-4 inhibitor such as roflumilast. (bvsalud.org)
  • We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. (bvsalud.org)
  • BACKGROUND: Roflumilast is the only approved oral phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease (COPD) in patients with chronic bronchitis and a history of frequent exacerbations. (bvsalud.org)
  • Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. (ox.ac.uk)
  • This includes a few exogenous, vertically transmitted and endogenous viruses of mice (type B) and some primate and sheep viruses (type D). MAMMARY TUMOR VIRUS, MOUSE is the type species. (bioportfolio.com)
  • It also significantly suppressed an increase in the number of total inflammatory cells, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, and tumor necrosis factor (TNF)- in bronchoalveolar lavage fluid (BALF) of the mice. (elsevier.com)
  • Analysis of short-term treatment with the phosphodiesterase type 5 inhibitor tadalafil on long bone development in young rats. (harvard.edu)
  • Male Wistar rats were fed a liquid diet containing ethanol as 35% of total calories or pair-fed a control diet that isocalorically substituted maltose dextrins for ethanol for 4 wk. (dundee.ac.uk)
  • Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. (tudelft.nl)
  • Apremilast is a drug for the treatment of certain types of psoriasis and psoriatic arthritis. (theartchics.com)
  • Apremilast (CC-10004) is an orally available inhibitor of type-4 cyclic nucleotide phosphodiesterase ( PDE-4 ) with an IC 50 of 74 nM. (medchemexpress.com)
  • A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. (harvard.edu)
  • A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. (bvsalud.org)
  • 42 , 43 Cyclic-AMP (cAMP) downmodulates this positive signaling wave by suppressing SYK and PI3Kδ activity. (bloodjournal.org)
  • Deletion of PC2 increases cAMP levels, which can be corrected by reexpression of wild-type PC2 but not by a mutant lacking calcium channel activity. (umn.edu)
  • The suppression in cAMP accumulation caused by ethanol feeding was associated with increased activity of phosphodiesterase 4. (dundee.ac.uk)
  • In conclusion, these data suggest that chronic ethanol feeding increased phosphodiesterase 4 activity in adipocytes, resulting in decreased accumulation of cAMP in response to beta-adrenergic activation and a suppression of beta-adrenergic stimulation of lipolysis. (dundee.ac.uk)
  • Two mechanisms have been proposed to produce localized elevations in cAMP, known as microdomains: impeded diffusion, and high phosphodiesterase (PDE) activity. (nih.gov)
  • screening (HTS) method for measuring cyclic nucleotide phosphodiesterase activity from. (joggingclubsablais.com)
  • Phosphodiesterase 5 Inhibition Limits Doxorubicin-induced Heart Failure by Attenuating Protein Kinase G Ia Oxidation. (harvard.edu)
  • Bjorgo E, Solheim SA, Abrahamsen H, Baillie GS, Brown KM, Berge T, Okkenhaug K, Houslay MD, Tasken K (2010) Cross talk between phosphatidylinositol 3-kinase and cyclic AMP (cAMP)-protein kinase a signaling pathways at the level of a protein kinase B/beta-arrestin/cAMP phosphodiesterase 4 complex. (springer.com)
  • Cyclic AMP (cAMP) and its main effector Protein Kinase A (PKA) are critical for several aspects of neuronal function including synaptic plasticity. (nih.gov)
  • Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural Studies of Vibrio Phosphodiesterase V-cGAP3. (harvard.edu)
  • Monocyte-to-macrophage differentiation with the cytokine granulocyte-macrophage colony-stimulating factor induces expression of the cyclic nucleotide phosphodiesterase PDE1B2. (pnas.org)
  • Fingerprint Dive into the research topics of 'Ni-catalyzed nucleophilic conjugate additions of Grignard and organozincate reagents to substituted 4-vinylpyridines. (princeton.edu)
  • This graph shows the total number of publications written about "Cyclic Nucleotide Phosphodiesterases, Type 5" by people in Harvard Catalyst Profiles by year, and whether "Cyclic Nucleotide Phosphodiesterases, Type 5" was a major or minor topic of these publication. (harvard.edu)
  • Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. (medchemexpress.com)
  • Theophylline is a nonselective phosphodiesterase (PDE) inhibitor, adenosine receptor blocker, and histone deacetylase (HDAC) activator. (medchemexpress.com)
  • Disruption of the CFTR-Shank2-phosphodiesterase 4D protein complex appeared to be mostly responsible for the changes in CFTR activities. (elsevier.com)
  • During the past three decades, a huge number of studies have reported that Human immunodeficiency virus type-1 (HIV-1) destroys the function of different cells in the blood that are involved in fighting bacterial, viral and fungal infections. (uab.edu)
  • This harmful heme has the ability to destroy the structure and function of several types of cells in the body. (uab.edu)
  • After secondary OVA challenge, RL significantly increased as did the number of lung inflammatory cells and IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF). (elsevier.com)
  • Cone cells constitute only 3% of the photoreceptors of the wild-type (WT) mouse. (rupress.org)
  • TY - JOUR T1 - The unrecognized effects of phosphodiesterase 4 on epithelial cells in pulmonary inflammation. (unboundmedicine.com)
  • We demonstrate that early postnatal NG2-expressing (NG2 + ) progenitor cells located in the SVZ self-renew in vitro and display phenotypic features of transit-amplifier type C-like multipotent cells. (rupress.org)
  • IRS1 and PDE1C are selectively expressed in sensory epithelial hair cells, whereas the other components are expressed in sensory epithelial supporting cells or in both cell types, as judged from co-expression or non-co-expression with glial fibrillary acidic protein, a marker for supporting cells. (forskningsdatabasen.dk)
  • Monocytes are peripheral immune cells that have the potential to differentiate into a variety of cell types depending on the combination of cytokines and stimuli to which they are exposed. (pnas.org)
  • The differentiated cell types range from professional antigen-presenting dendritic cells to osteoclasts to various macrophage populations found throughout the body ( 1 - 3 ). (pnas.org)
  • However, addition of IL-4 in the presence of GM-CSF changes the differentiation to a dendritic cell and suppresses PDE1B2 up-regulation ( 10 , 12 ). (pnas.org)
  • The Haase team could show that they are fine tuning signaling by Toll-like receptor 4, promoting the secretion of pro-inflammatory cytokines, whereas they downregulate the production of type-1 interferons and nitric monoxide. (uni-potsdam.de)
  • 7. These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion. (strath.ac.uk)