Cyclic Nucleotide Phosphodiesterases, Type 1: 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.3',5'-Cyclic-AMP Phosphodiesterases: 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.Cyclic Nucleotide Phosphodiesterases, Type 4: 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.Cyclic Nucleotide Phosphodiesterases, Type 3: 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.Cyclic Nucleotide Phosphodiesterases, Type 2: 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.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.2',3'-Cyclic-Nucleotide Phosphodiesterases: 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.-.Nucleotides, CyclicPhosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.Cyclic Nucleotide Phosphodiesterases, Type 5: 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.Cyclic GMP: 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)Cyclic Nucleotide Phosphodiesterases, Type 7: 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.Cyclic AMP: 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.Rolipram: A phosphodiesterase 4 inhibitor with antidepressant properties.1-Methyl-3-isobutylxanthine: 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 KINASESPurinonesIsoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Molecular Sequence Data: 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.Calmodulin: 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.Amino Acid Sequence: 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.Kinetics: The rate dynamics in chemical or physical systems.Cyclic Nucleotide Phosphodiesterases, Type 6: 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.Nucleotides: 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)Phosphodiesterase 3 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 3.Phosphodiesterase 4 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 4.4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.Dibutyryl Cyclic GMP: 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.Theophylline: 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.Phosphodiesterase I: 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.Cyclic Nucleotide-Gated Cation Channels: 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.Phosphorus-Oxygen Lyases: Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.Milrinone: 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.Bucladesine: 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)Pyrrolidinones: 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)Adenine NucleotidesCyclic AMP-Dependent Protein Kinases: 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.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Second Messenger Systems: 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.Papaverine: 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.Cyclic IMP: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Colforsin: 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.Guanylate Cyclase: 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.Cloning, Molecular: 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.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Phosphodiesterase 5 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 5.8-Bromo Cyclic Adenosine Monophosphate: 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.Calcium: 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.Guanine NucleotidesCattle: 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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Isoproterenol: 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.Xanthines: Purine bases found in body tissues and fluids and in some plants.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Signal Transduction: 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.Vinca Alkaloids: 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.Cyclic P-OxidesEnzyme Activation: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells. (1/326)

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)

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytes. (2/326)

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)

Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin. (3/326)

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)

Inhibition of phosphodiesterase III with milrinone increases renin secretion in human subjects. (4/326)

One of the major signaling molecules involved in the regulation of renin secretion is cyclic AMP (cAMP). The concentration of cAMP in cells is determined in part by the rate of cAMP hydrolysis by several families of phosphodiesterases, especially the phosphodiesterase III family, but little is known about the roles of these enzymes in the control of renin secretion, particularly in humans. The aim of the present study was to investigate the effect of the phosphodiesterase III inhibitor milrinone on renin secretion in human subjects. Milrinone was infused i.v. in eight healthy normotensive subjects in a dose of 100 microgram/kg. Immediately after the infusion, there was a transient increase in systolic pressure from 107 +/- 5 to 116 +/- 5 mm Hg (p <.01), but no significant change in diastolic or mean arterial pressure. Heart rate increased from 67 +/- 2 to 86 +/- 4 beats/min (p <.01) and remained elevated. Plasma renin activity increased in all subjects, the mean value increasing from 3.0 +/- 0.5 to 6.0 +/- 1.1 ng/ml/h at 15 min (p <.01). These results demonstrate that milrinone increases renin secretion in human subjects, thus providing evidence that phosphodiesterase III family participates in the control of renin secretion in humans. The increase in renin secretion does not appear to be mediated by major mechanisms that control renin secretion, and likely results from an increase in cAMP concentration in the juxtaglomerular cells.  (+info)

Phosphorylation and activation of phosphodiesterase type 3B (PDE3B) in adipocytes in response to serine/threonine phosphatase inhibitors: deactivation of PDE3B in vitro by protein phosphatase type 2A. (5/326)

Phosphodiesterase type 3B (PDE3B) has been shown to be activated and phosphorylated in response to insulin and hormones that increase cAMP. In order to study serine/threonine protein phosphatases involved in the regulation of rat adipocyte PDE3B, we investigated the phosphorylation and activation of PDE3B in vivo in response to phosphatase inhibitors and the dephosphorylation and deactivation of PDE3B in vitro by phosphatases purified from rat adipocyte homogenates. Okadaic acid and calyculin A induced dose- and time-dependent activation of PDE3B. Maximal effects were obtained after 30 min using 1 microM okadaic acid (1.8-fold activation) and 300 nM calyculin A (4-fold activation), respectively. Tautomycin and cyclosporin A did not induce activation of PDE3B. Incubation of adipocytes with 300 nM calyculin A inhibited protein phosphatase (PP) 1 and PP2A completely. Okadaic acid (1 microM) reduced PP2A activity by approx. 50% but did not affect PP1 activity, and 1 microM tautomycin reduced PP1 activity by approx. 60% but PP2A activity by only 11%. This indicates an important role for PP2A in the regulation of PDE3B. Furthermore, rat adipocyte PDE3B phosphatase activity co-purified with PP2A but not with PP1 during MonoQ chromatography. As compared with insulin, okadaic acid and calyculin A induced phosphorylation of PDE3B by 2.8- and 14-fold respectively, whereas tautomycin and cyclosporin A had no effect. Both calyculin A and okadaic acid induced phosphorylation on serine 302, the site known to be phosphorylated on PDE3B in response to insulin and isoproterenol (isoprenaline), as well as on sites not identified previously. In summary, PP2A seems to be involved in the regulation of PDE3B in vivo and can act as a PDE3B phosphatase in vitro. In comparison with insulin, calyculin A induced a dramatic activation of PDE3B and both calyculin A and okadaic acid induced phosphorylation on additional sites, which could have a role in signalling pathways not yet identified.  (+info)

Beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors: shifting the focus from inotropy to cyclic adenosine monophosphate. (6/326)

Clinical trials of beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors in heart failure have demonstrated a reduction in survival in treated patients despite initial inotropic responses. These findings have led many to infer that activation of the mechanisms through which contractility is increased has deleterious effects on failing myocardium. It should be remembered, however, that these agents act proximately by raising intracellular cyclic adenosine monophosphate (cAMP) content and stimulating protein phosphorylation by cAMP-dependent protein kinase, and that the proteins whose phosphorylation contributes to the inotropic responses may be different from the proteins whose phosphorylation contributes to the reduction in survival. Evidence in support of the latter interpretation is presented, and potential therapeutic approaches through which the phosphorylation of different proteins might be selectively affected are considered.  (+info)

(-)-Enantiomer EMD 57439 antagonizes the Ca2+ sensitizing effect of (+)-enantiomer EMD 57033 on diastolic function but not on systolic function in rabbit ventricular cardiomyocytes. (7/326)

EMD 53998 (5-[1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydro-6-quinolyl]-6-meth yl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one), the racemic mixture of (+)-enantiomer EMD 57033 and (-)-enantiomer EMD 57439, is a prototype of Ca2+ sensitizers that act via a central and/or down-stream mechanism in cardiac E-C coupling. In rabbit ventricular cardiomyocytes loaded with indo-1/AM, EMD 53998 and EMD 57033 shifted the relationship between Ca2+ transients and cell shortening (systolic function) to the left to the same extent as compared with that of elevation of [Ca2+]o. EMD 57439 did not elicit a positive inotropic effect (PIE). The PIE of EMD 57033 was associated with a more pronounced decrease in the diastolic cell length than that of EMD 53998, whereas the systolic effects of these compounds were equivalent. These results indicate that weak phosphodiesterase (PDE) III inhibition may exert a differential action on diastolic and systolic function. Thus, EMD 57439 antagonizes the Ca2+-sensitizing effect of EMD 57033 on diastolic function with no effect on systolic function, which may lead to a decrease in diastolic cell length of a lesser extent with the racemate EMD 53998 compared with (+)-enantiomer EMD 57033.  (+info)

Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. (8/326)

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is important for insulin-induced activation of PDE3B.  (+info)

0139] The dosage forms of the invention can be employed for the treatment and prevention of all diseases regarded as treatable or preventable through the use of PDE 4 inhibitors. Selective cyclic nucleotide phosphodiesterase (PDE) inhibitors (specifically of type 4) are suitable on the one hand as bronchial therapeutic agents (for the treatment of airway obstructions owing to their dilating effect but also owing to their effect increasing the respiratory rate and respiratory drive) and for eliminating erectile dysfunction owing to the vasodilating effect, but on the other hand especially for the treatment of disorders, especially of an inflammatory nature, e.g. of the airways (asthma prophylaxis), of the skin, of the central nervous system, of the intestine, of the eyes and of the joints, which are promoted by mediators such as histamine, PAF (platelet-activating factor), arachidonic acid derivatives such as leukotrienes and prostaglandins, cytokines, interleukins, chemokines, alpha-, beta- and ...
Minami N, Suzuki Y, Yamamoto M, Kihira H, Imai E, Wada H, Kimura Y, Ikeda Y, Shiku H, Nishikawa M.; Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo.; Life Sci. , 1997 PubMed Europe PMC ...
The human platelet cilostamide- and cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) was rapidly purified approximately 19,000-fold to apparent homogeneity using single step affinity chromatography on the isothiocyanate derivative of cilostamide coupled to aminoethyl agarose. Within 24 h, 30 micrograms of enzyme protein was obtained from 20 ml of packed platelets. Vmax for cAMP and cGMP was 6.1 and 0.9 mumol/min per mg protein, respectively. Several polypeptides (110/105, 79, 62, 55/53 kDa) were identified after SDS-PAGE, all of which were immunologically related to cGI-PDE and represented approx. 5, 20, 50 and 20% of the total protein, respectively. Limited proteolysis of the cGI-PDE with chymotrypsin produced a major fragment of approximately 47 kDa (and at least two smaller peptides) with catalytic activity and sensitivity to cGMP and OPC 3911 similar to controls. Phosphorylation of the cGI-PDE by cAMP-dependent protein kinase (A-kinase) resulted in maximal incorporation of 0.6-1.8 mol of ...
Intracellular cAMP levels are higher in LDLR-/−p110γ−/− than in LDLR−/−p110γ+/−macrophages.LDLR−/−p110γ+/− and LDLR−/−p110γ−/− BMM
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. ...
TY - JOUR. T1 - Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukemia. AU - Zhang, Lingzhi. AU - Murray, Fiona. AU - Zahno, Anja. AU - Kanter, Joan R.. AU - Chou, Daisy. AU - Suda, Ryan. AU - Fenlon, Michael. AU - Rassenti, Laura. AU - Cottam, Howard. AU - Kipps, Thomas J.. AU - Insel, Paul A.. PY - 2008/12/9. Y1 - 2008/12/9. N2 - Cyclic nucleotide phosphodiesterase (PDE) isoforms can influence disease pathogenesis and be novel therapeutic targets. Because lower cAMP levels may contribute to the decreased apoptosis that occurs in chronic lymphocytic leukemia (CLL), we assessed the expression levels of PDE isoforms in peripheral blood mononuclear cells (PBMC) of healthy adults and patients with CLL. We found a unique PDE mRNA signature in CLL: higher levels than in normal PBMC of PDE7B (increased approximate to 23-fold) and lower levels of PDE3B, 4D, 5A, and 9A mRNA (each decreased approximate to 30-fold). Increased ...
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MacPherson, Tara and Armstrong, Jane and Criddle, David and Wright, Karen (2014) Physiological intestinal oxygen modulates the Caco-2 cell model and increases sensitivity to the phytocannabinoid cannabidiol. In Vitro Cellular and Developmental Biology - Animal, 50 (5). pp. 417-426. ISSN 1071-2690 Maki, Takakuni and Okamoto, Yoko and Carare, Roxana O. and Hase, Yoshiki and Hattori, Yorito and Hawkes, Cheryl A. and Saito, Satoshi and Yamamoto, Yumi and Terasaki, Yasukazu and Ishibashi-Ueda, Hatsue and Taguchi, Akihiko and Takahashi, Ryosuke and Miyakawa, Taihei and Kalaria, Raj N. and Lo, Eng H. and Arai, Ken and Ihara, Masafumi (2014) Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid. Annals of Clinical and Translational Neurology, 1 (8). pp. 519-533. ISSN 2328-9503 Mann, Elizabeth R. and Bernardo, David and Ng, Siew C. and Rigby, Rachael J. and Al-hassi, Hafid O. and Landy, Jon and Peake, Simon T. C. and Spranger, Henning and English, Nicholas R. and Thomas, Linda ...
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The 2020 Gordon Research Seminar on Cyclic Nucleotide Phosphodiesterases (GRS) will be held in Les Diablerets, Switzerland. Apply today to reserve your spot.
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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 PDE7B gene encodes 35-cyclic nucleotide phosphodiesterase (PDE) and a known target in cognitive impairments. Therefore, it is of interest to design and development of potential inhibitors with PDE7B with improved binding features. We document that the amino acid residues such as H186, K190, and G113 of PDE7B protein showed crucial interactions with aspirin for further consideration in this context.
Key non-adrenergic cardiovascular drugs include vasopressin (and its analogues, teripressin and ornipressin), phosphodiesterase III inhibitors such as milrinone, and calcium sensitisers such as levosimendan.. ...
Mitochondrial damage and dysfunction are major pathophysiological mechanisms underlying acute kidney injury (AKI). Following various forms of AKI, mitochondrial biogenesis, the de novo generation of new, functional mitochondria, is suppressed. Pharmacological stimulation of PPARγ-coactivator-1α (PGC-1α), the master regulator of mitochondrial biogenesis, promotes recovery of mitochondrial and renal function after AKI. The primary goals of this project were the evaluation of renal cGMP as a modulator of mitochondrial biogenesis in AKI, and the assessment of phosphodiesterase (PDE) inhibitors and guanylyl cyclase (GC) activators as novel agents to induce mitochondrial biogenesis and promote renal recovery. cGMP has been demonstrated to stimulate mitochondrial biogenesis and function. Both cGMP generation through guanylyl cyclase and degradation through PDEs are highly regulated processes. Compounds that regulate cGMP levels, including the PDE3 inhibitors cilostamide and trequinsin, and the PDE5 ...
Mitochondrial damage and dysfunction are major pathophysiological mechanisms underlying acute kidney injury (AKI). Following various forms of AKI, mitochondrial biogenesis, the de novo generation of new, functional mitochondria, is suppressed. Pharmacological stimulation of PPARγ-coactivator-1α (PGC-1α), the master regulator of mitochondrial biogenesis, promotes recovery of mitochondrial and renal function after AKI. The primary goals of this project were the evaluation of renal cGMP as a modulator of mitochondrial biogenesis in AKI, and the assessment of phosphodiesterase (PDE) inhibitors and guanylyl cyclase (GC) activators as novel agents to induce mitochondrial biogenesis and promote renal recovery. cGMP has been demonstrated to stimulate mitochondrial biogenesis and function. Both cGMP generation through guanylyl cyclase and degradation through PDEs are highly regulated processes. Compounds that regulate cGMP levels, including the PDE3 inhibitors cilostamide and trequinsin, and the PDE5 ...
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 ...
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 ...
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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One of the mechanisms by which cilostazol reduces restenosis after PTCA is thought to be inhibition of neointimal proliferation, considered a major mechanism of restenosis after PTCA caused by SMC migration, proliferation, and matrix synthesis.3 4 22 SMC migration and proliferation are induced by growth factors released from activated platelets. As an antiplatelet medication, cilostazol controls the induction by platelet-derived growth factors.12 13 23 More importantly, cilostazol is thought to directly inhibit SMC growth. In vitro studies involving rat aortic smooth muscle cell cultures have shown that increasing the concentration of cilostazol resulted in an increase of intracellular cAMP and a decrease of 3H-thymidine uptake,23 suggesting that phosphodiesterase III inhibitors inhibit SMC growth by affecting its deoxyribonucleic acid, thereby controlling its cell proliferation.24 This direct inhibition of SMC proliferation is considered to be the main contributor to the significant reduction ...
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 ...
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.
Resveratrol, a polyphenol most notably found in red wine has anti-aging properties in mice fed a high-fat diet; resveratrol protects against obesity and type 2 diabetes. Several clinical trials have been conducted to study the metabolic effects of resveratrol. Although these trials have used different subject groups (e.g. obese healthy, type 2 diabetics or older adults with glucose intolerance), they suggest that resveratrol may improve insulin sensitivity. However, the therapeutic potential of resveratrol is diminished by the fact that it has a very promiscuous target profile. In order to translate resveratrol biology into clinical application, it is helpful to identify the cellular target(s) of resveratrol that mediate the desired effects and to develop therapies specific for that target(s). Recently, we discovered that the metabolic effects of resveratrol appear to result from competitive inhibition of cAMP-degrading phosphodiesterases (PDEs), which increases cAMP levels. The cAMP-dependent ...
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 ...
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
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. ...
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 ...
PDE8B - PDE8B (untagged)-Human phosphodiesterase 8B (PDE8B), transcript variant 2 available for purchase from OriGene - Your Gene Company.
cAMP-specific 3,5-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene. This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. Altered activity of this protein has been associated with schizophrenia and bipolar disorder. PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram. PDE4B is involved in dopamine-associated and stress-related behaviours. It has ...
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 ...
Definition of 2,3-cyclic-nucleotide phosphodiesterases in the Definitions.net dictionary. Meaning of 2,3-cyclic-nucleotide phosphodiesterases. What does 2,3-cyclic-nucleotide phosphodiesterases mean? Information and translations of 2,3-cyclic-nucleotide phosphodiesterases in the most comprehensive dictionary definitions resource on the web.
We have resolved multiple forms of cyclic nucleotide phosphodiesterase (PDE) in whole rat ventricle and in isolated rat ventricular myocytes by use of anion-exchange high-performance liquid chromatography. One major form, the soluble calmodulin-stimulated PDE, is apparently absent from isolated myocytes. We discern four peaks of PDE activity (designated A-D in the order of their elution) in a soluble fraction obtained from whole rat ventricle. Peak A is stimulated twofold to threefold by the addition of calcium and calmodulin (Ca2+/CalM) and preferentially hydrolyzes cGMP over cAMP (in the presence of Ca2+/CalM, KmcGMP = 1.5 microM, KmcAMP = 17 microM). Peak B has similar affinities for both cAMP and cGMP (half-maximum velocities achieved at 30 microM substrate) and demonstrates positive cooperativity with cAMP but not with cGMP. The hydrolysis of cAMP by peak B is stimulated by cGMP at substrate concentrations up to 20 microM; the maximum effect is seen at 1 microM cAMP (25-fold stimulation by ...
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Pde4d - Pde4d (GFP-tagged) - Mouse phosphodiesterase 4D cAMP specific (Pde4d), (10ug) available for purchase from OriGene - Your Gene Company.
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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Cyclic nucleotide phosphodiesterases (PDEs) are the only enzymes that degrade the cyclic nucleotides cAMP and cGMP, and play a key role in modulating the amplitude and duration of the signal delivered by these two key intracellular second messengers. Defects in cyclic nucleotide signalling are known to be involved in several pathologies. As a consequence, PDEs have long been recognized as potential drug targets, and they have been the focus of intense research for the development of therapeutic agents. A number of PDE inhibitors are currently available for the treatment of disease, including obstructive pulmonary disease, erectile dysfunction, and heart failure. However, the performance of these drugs is not always satisfactory, due to a lack of PDE-isoform specificity and their consequent adverse side effects. Recent advances in our understanding of compartmentalised cyclic nucleotide signalling and the role of PDEs in local regulation of cAMP and cGMP signals offers the opportunity for the development
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. ...
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a high affinity for both cAMP and cGMP.
The IUPHAR/BPS Guide to Pharmacology. phosphodiesterase 4D - Phosphodiesterases, 3,5-cyclic nucleotide (PDEs). Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
3,5-cyclic-AMP phosphodiesterases, 3,5-cyclic-GMP phosphodiesterases, animals, cyclic GMP, cyclic nucleotide phosphodiesterases, type 1, cyclic nucleotide phosphodiesterases, type 5, enzyme activation, GTP-binding proteins, guanylyl imidodiphosphate, isoenzymes, lung, muscle, smooth, phosphoric diester hydrolases, phosphorylation, protein kinases, signal transduction, Pharmacy and materia medica, ...
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?
The aim of this study was to evaluate the efficacy and safety of enoximone, an imidazolonic compound inhibiting cardiac phosphodiesterase III, during the postoperative period. The drug was administered prior to the usual stages of weaning the patient off extracorporeal circulation, to a group of 20 subjects who presented an ejection fraction of less than 35% following hemodynamic studies. Patients were randomly subdivided into 4 groups each of which received a different dose of enoximone according to the following protocol: Group A, 1 mg/kg bolus and slow infusion at 10 gamma/kg/min; Group B, 0.5 mg/kg bolus and slow infusion at 15 gamma/kg/min; Group C, 0.5 mg/kg bolus and slow infusion at 10 gamma/kg/min; Group D, slow infusion at 10 gamma/kg/min. The best results in hemodynamic terms and with regard to the positive inotropic and vasodilatory action of the drug in question were obtained in Group C. Increased cardiac output was observed in all patients within 120 minutes of enoximone administration and
Background: The two enzyme families involved in the spatiotemporal control of intracellular cAMP are adenylyl cyclases (AC) which account for its synthesis and phosphodiesterases (PDE) which account for its degradation. In adult cardiomyocytes, AC5 and AC6, and PDE3 and PDE4 are the major isoforms of these two enzyme families, respectively. In addition to their role in modulating cardiac contractile function, AC5 and AC6 are differentially regulated in response to different cardiac stress. However the role of each cyclase in cardioprotection is still controversial. Dynamic inter-regulation between ACs and PDEs has never been investigated yet. In this study, we aimed to determine the effect of AC5 and AC6 overexpression on submembrane PDE3 related cAMP hydrolysis in response to β-adrenergic receptor stimulation.. Methods and Results: Mice with cardiac specific overexperssion of AC5 (AC5Tg) and AC6 (AC6Tg) were produced. The spatiotemporal dynamics of cAMP were determined on both AC5Tg and AC6Tg ...
BAY-60-7550 is a potent PDE2 inhibitor with IC50 values of 2.0 nM (bovine) and 4.7 nM (human). BAY-60-7550 antagonizes oxidative stress-induced anxiety-like behavioral effects in mice by increasing cGMP signaling. Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP/cGMP levels. These second messengers play important regulatory roles in controlling steroidogenesis in the adrenal. Disruption of PDEs has been associated with a number of adrenal diseases
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Calmodulin-dependent phosphodiesterase (CaMPDE) is one of the key enzymes involved in the complex interactions which occur between the cyclic-nucleotide and Ca2+ second-messenger systems. Calmodulin-dependent phosphodiesterase exists in different isoenzymic forms, which exhibit distinct molecular and/or catalytic properties. The kinetic properties suggest that the 63 kDa brain isoenzyme is distinct from the brain 60 kDa and heart and lung CaMPDE isoenzymes. The CaMPDE isoenzymes of 60 kDa from brain, heart and lung are regulated by calmodulin, but the affinities for calmodulin are different. At identical concentrations of calmodulin, the bovine heart CaMPDE isoenzyme is stimulated at a much lower Ca2+ concentration than the bovine brain or lung isoenzymes. The bovine lung CaMPDE isoenzyme contains calmodulin as a tightly bound subunit, so that a change in calmodulin concentration had no effect on the [Ca2+]-dependence of activation of this isoenzyme. These observations are consistent with the ...
Abstract of the Disclosure |p|Human, rat and mouse cAMP phosphodiesterase isoforms (denoted PDE4D7s), as well as the DNA (RNA) encoding such polypeptides, are disclosed. Also disclosed are methods for
... is a vasodilator that works by relaxing the muscles in your blood vessels to help them dilate (widen). This lowers blood pressure and allows blood to flow more easily through your veins and arteries. Milrinone is used as a short-term treatment for life-threatening heart failure. Milrinone may also be used for...
Complete information for PDE6B gene (Protein Coding), Phosphodiesterase 6B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
RecName: Full=Calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase 1A; Short=Cam-PDE 1A; EC=3.1.4.17;AltName: Full=61 kDa Cam-PDE; Short=hCam-1 ...
RecName: Full=Calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase 1B; Short=Cam-PDE 1B; EC=3.1.4.17;AltName: Full=63 kDa Cam-PDE ...
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TY - JOUR. T1 - Original Research. T2 - Role of phosphodiesterases in modulation of BK Ca channels in hypertensive pulmonary arterial smooth muscle. AU - Zhu, Shu. AU - White, Richard E.. AU - Barman, Scott A. PY - 2008/1/1. Y1 - 2008/1/1. N2 - BK Ca channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK Ca channels, but little is known about PKC-mediated modulation of BK Ca channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BK Ca channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BK Ca channels in FHR PASMC, which was blocked by PKC activation, and reversed by the phosphodiesterase (PDE) inhibitors IBMX, milrinone, and zaprinast. PDE inhibition also blocked the vasoconstrictor response to PKC activation in FHR pulmonary arteries. These results indicate that PKC inhibits cAMP-induced ...
TY - JOUR. T1 - Differential regulation of gene expression and insulin-induced activation of phosphodiesterase 3B in adipocytes of lean insulin-resistant IRS-1 (-/-) mice. AU - Hasegawa, Masaaki. AU - Tang, Yan. AU - Osawa, Haruhiko. AU - Onuma, Hiroshi. AU - Nishimiya, Tatsuya. AU - Ochi, Masaaki. AU - Terauchi, Yasuo. AU - Kadowaki, Takashi. AU - Makino, Hideichi. PY - 2002/11/1. Y1 - 2002/11/1. N2 - Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the antilipolytic action of insulin. PDE3B gene expression is generally reduced in adipocytes of either monogenic or polygenic rodent models of obese, insulin-resistance. An increased fat cell size, a common feature of obesity, could account for this reduction. Insulin receptor substrate-1 (IRS-1) (-/-) mice are lean with a reduced fat cell size and have insulin resistance due to a primary defect of insulin signaling. To determine whether the regulation of PDE3B gene expression is correlated with fat cell size, we examined ...
For patients who have two [C-11]rolipram PET scans, one before and another after SSRI treatment, previous failures of or intolerance to SSRI may not allow for treatment in the current protocol. In clinical practice, medication can be switched between sertraline and citalopram/escitalopram because sertraline and citalopram/escitalopram have somewhat different therapeutic effects and adverse reactions. Along these lines, we will consider citalopram and its enantiomer escitalopram as being equivalent to each other. Patients will therefore be excluded from the study with two [C-11]rolipram PET scans if they previously failed to respond to adequate treatment trials of all medications available for use in the study, or if they have a history of being unable to tolerate all of the study medications. Specifically, patients will be excluded from the study with two [C-11]rolipram PET scans if they:. j) previously proved unresponsive to therapeutic trials of both sertraline and ...
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.
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PDE10A functions as a dual-substrate enzyme, acting to degrade both cGMP and cAMP (Bender and Beavo, 2006). Therefore, the effects observed following TP-10 administration may have been mediated by either or both of these cyclic nucleotides. Several studies published by our laboratory and others have shown that, under physiological conditions, drugs that elevate cAMP or cGMP concentrations in MSNs (e.g., PDE inhibitors, cyclase activators, NO generators in the case of cGMP) augment spontaneous and evoked corticostriatal transmission (Threlfell and West, 2013). Furthermore, studies using zaprinast or papaverine to inhibit PDEs, which selectively degrade cGMP, have shown that PDE inhibition robustly facilitates corticostriatal transmission (Threlfell and West, 2013). Thus, intracellular injection of zaprinast or papaverine increased the duration of spontaneous "up states" driven in the intact striatum by cortical activity and depolarized the resting membrane potential of striatal MSNs. Conversely, ...
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pep:novel chromosome:VEGA66:4:102087543:102605833:1 gene:OTTMUSG00000008053 transcript:OTTMUST00000018212 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Pde4b description:phosphodiesterase 4B, cAMP specific ...
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... 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 ... 8 (3): 182-193. doi:10.1038/nrn2093. PMC 1887812 . PMID 17311005. Burgoyne RD, O'Callaghan DW, Hasdemir B, Haynes LP, Tepikin ...
2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... 2006). "Subcellular localization and regulation of type-1C and type-5 phosphodiesterases". Biochem. Biophys. Res. Commun. 341 ( ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ... cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. GRCh38: Ensembl release 89: ...
"Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine ... which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2). "Sigma Aldrich". ... adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes". Mol Pharmacol. 48 (1): 121-130. PMID ... Méry, PF; Pavoine, C; Pecker, F; Fischmeister, R (1995). "Erythro-9-(2-hydroxy-3-nonyl) ...
Cyclic-nucleotide 3'-phosphodiesterase. Moreover, oligodendrocytes also developed and migrated into fiber bundles in mice when ... 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 endoermal cell types. The cellular ... 560 (1-3): 192-8. doi:10.1016/S0014-5793(04)00086-9. PMID 14988021. Tan, Y; Xie, Z; Ding, M; Wang, Z; Yu, Q; Meng, L; Zhu, H; ...
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 ...
Modulates the activity of membrane-bound enzymes: phosphodiesterase, cyclic nucleotides, adenylate cyclase, aldoreductase, ... Its chemical structure resembles that of pyridoxine (a type of vitamin B6). It is not approved for any medical use in the ... doi:10.1007/s11055-012-9646-3. Dumayev K.M., Voronina T.A., Smirnov L.D. antioxidants in the prophylaxis and therapy of CNS ... Emoxypine (2-ethyl-6-methyl-3-hydroxypyridine), also known as Mexidol or Mexifin when used as the succinate salt, is an ...
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, ...
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic ... The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". ... Moustafa F, Feldman SR (May 2014). "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4- ...
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 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 ...
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 ... cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene. The protein encoded by this gene ... "Entrez Gene: PDE9A phosphodiesterase 9A". Verhoest PR, Fonseca KR, Hou X, et al. (2012). "Design and discovery of 6-[(3S,4S)-4- ...
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. The PDE3 ... Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ...
"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 2013 Feb 15;339(6121 ... cGAMP was found to be much more potent than other cyclic di-nucleotides (c-di-GMP and c-di-AMP). cGAMP was shown to ... phosphodiesterases. Other advantages of the unique 2'-5' linkage may be that cGAMP is able to bind multiple allelic variants of ... Cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide (CDN) and the first to be found in metazoans. Other CDNs (c-di-GMP and c-di-AMP ...
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 ... 3: 96-9. doi:10.4024/18SH03R.jbpc.03.03. This article incorporates text from the United States National Library of Medicine, ... The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that ...
... is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. ... Bucladesine (50-100nM/mouse) showed significant attenuation in the morphine withdrawal syndrome in the wild-type mice. In ... the effect of bucladesine as a cAMP analog has been studied on the pentylenetetrazol-induced seizure in the wild-type mice. The ... 670 (2-3): 464-70. doi:10.1016/j.ejphar.2011.09.026. PMID 21946102. Seyedi SY, Salehi F, Payandemehr B, Hossein S, Hosseini- ...
Essayan DM (2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi ... effect of pentoxifylline as a phosphodiestrase inhibitor was study on the pentylenetetrazol-induced seziure in the wild-type ... Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which ... the effects of non-specific phosphodiesterase inhibition". Clinics. 63 (3): 321-8. doi:10.1590/S1807-59322008000300006. PMC ...
Methylxanthines such as caffeine inhibit the action of cyclic nucleotide phosphodiesterase, which normally acts to break down ... Symptoms must also not have a more likely clinical cause, such as another type of anxiety disorder, come before the ingestion ... Cyclic adenosine monophosphate, or cAMP, is a second messenger important in many cellular processes and is a critical factor in ... Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease ...
... by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). One manifestation of depression is an ... 5-cyclic adenosine monophosphate (cAMP) system induced by different types of chronic but not acute antidepressant treatment, ... a type of glutamate receptor - produces rapid (within 2 hours), robust and sustained (lasting for up to a fortnight) ... "Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor ...
... cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 ... Journal of Cyclic Nucleotide Research. 2 (3): 139-48. PMID 6493. Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless ... There are two types of photoreceptors: cones and rods. The rod and cone PDE6 complexes have different structures. PDE6β ... Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase]". Bioorganicheskaia Khimiia ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". J. Allergy Clin. Immunol. 108 (5): 671-80. doi:10.1067/mai. ... Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects". J. Biol. Chem. 281 (20): 14192-206. doi: ... "Binding and Functional Comparisons of Two Types of Tumor Necrosis Factor Antagonists". Journal of Pharmacology and Experimental ... 65 (3): 890-8. doi:10.1016/j.ijrobp.2006.03.025. PMID 16751071. Gulcubuk A, Altunatmaz K, Sonmez K, Haktanir-Yatkin D, Uzun H, ...
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication" ( ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ... of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793-812. doi ...
The GTP form of the α subunit of transducin (Gt) activates the cyclic GMP phosphodiesterase from retinal rod outer segments, ... Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". Proc ... They can also activate L-type calcium channels, as in H3 receptor pharmacology. Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H ... The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved ...
... cyclic-nucleotide phosphodiesterase EC 3.1.4.18: now EC 3.1.16.1 EC 3.1.4.19: now EC 3.1.13.3 EC 3.1.4.20: now EC 3.1.13.1 EC ... type I site-specific deoxyribonuclease EC 3.1.21.4: type II site-specific deoxyribonuclease EC 3.1.21.5: type III site-specific ... CMP-N-acylneuraminate phosphodiesterase EC 3.1.4.41: sphingomyelin phosphodiesterase D EC 3.1.4.42: glycerol-1,2-cyclic- ... glucose-1-phospho-D-mannosylglycoprotein phosphodiesterase EC 3.1.4.52: cyclic-guanylate-specific phosphodiesterase EC 3.1.4.53 ...
"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor" (pdf). British ... 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. ...
Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... Sildenafil (Viagra) is an inhibitor of cGMP-specific phosphodiesterase type 5, which enhances the vasodilatory effects of cGMP ... "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases ...
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. and Weiss, B.: 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. ...
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. ...
"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. PDE2 ... June 1997). "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ...
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ... Type I PDE are activated by the binding of calmodulin in the presence of Ca2+. ... calmodulin-dependent cyclic-nucleotide phosphodiesterase activity Source: MGIInferred from sequence orthologyi*7568196 ... Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ...
Hagiwara M, Endo T, Hidaka H Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle . Biochem ... show that Vinpocetine, a phosphodiesterase (PDE) inhibitor known for its minimal side effects and great potential in cognitive ... Solntseva EI, Bukanova JV, Skrebitsky VG The nootropic drug vinpocetine modulates different types of potassium currents in ... Chiu PJ, et al Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and 45Ca-fluxes in the rabbit aorta . ...
... cyclic nucleotide 3 phosphodiesterase ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations ... cyclic nucleotide 3 phosphodiesterase ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody ... cyclic nucleotide 3 phosphodiesterase ELISA ELISA Kit across 10 suppliers. ... C-Type Natriuretic Peptide ELISA Kit *. Detection Target: C-Type Natriuretic Peptide ...
2002 Feb 15;46(3):278-86. Research Support, Non-U.S. Govt; Research Support, U.S. Govt, P.H.S. ... Publication types, MeSH terms, Substance, Grant support. Publication types. *Research Support, Non-U.S. Govt ... Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of enzymes that were previously divided by their primary ... Cyclic nucleotide phosphodiesterases class III: members, structure, and catalytic mechanism.. Richter W1. ...
07/01/2000 - "The effects of a novel Ca(2+)-sensitizer (EMD 60263, 10 microM, group 1) were compared with a phosphodiesterase ( ... Type 3 Cyclic Nucleotide Phosphodiesterases 2. 1,2,3,4-tetrahydroquinoline 3. zatebradine ... a Ca2+ sensitizer without phosphodiesterase III inhibitory properties, increased contractility more profoundly in stunned than ... sensitizing agent with negligible phosphodiesterase III inhibitory activity, on diastolic function of regionally stunned ...
Cyclic nucleotide research: still expanding after half a century. Nat Rev Mol Cell Biol. 2002; 3: 710-718. ... Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res. 2003; 93: 280-291. ... cAK indicates cAMP-dependent protein kinase; cGK(I/II), cGMP-dependent protein kinase (type I/II); cGMP, cyclic guanosine-3′,5 ... Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene ...
Functional regulatory T cells produced by inhibiting cyclic nucleotide phosphodiesterase type 3 prevent allograft rejection. ... If development into CTL occurs within the graft, the question arises as to which types of graft cells stimulate this process. ... Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. ... or type III (transmural arteritis) (44). The presence and degree of such vascular lesions is reported to correlate with the ...
Protein Type. Unknown. Biological Properties. General Function. Involved in catalytic activity. Specific Function. Cyclic ... cyclic nucleotide phosphodiesterase 1C (HMDBP00605). IdentificationBiological propertiesGene propertiesProtein properties ... cyclic nucleotide phosphodiesterases. J Biol Chem. 1996 Jan 12;271(2):796-806. [PubMed:8557689 ] ... nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many ...
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 3′-phosphodiesterase modulates cell morphology. J. Neurosci. Res. 39, 386 - 397. *Wiley Online Library , ... phosphodiesterase isoform 2 and identification of specifically phosphorylated serine residues. J. Neurochem. 74, 540 - 546. * ... 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; ...
Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication.. null 17 ... The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second ... 35-cyclic nucleotide phosphodiesterase, catalytic domain superfamily (IPR036971). Short name: PDEase_catalytic_dom_sf ... They regulate the localisation, duration and amplitude of cyclic nucleotide signalling within subcellular domains. PDEs are ...
Kakkar R, Raju RVS, Sharma RK (1999) Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1). Cell Mol Life Sci 55: ... Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure. Alexandre E. ... Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure ... Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure ...
... cyclic nucleotide 3 phosphodiesterase. Locus17q21.2. Discovery year1991-07-15 ... Alternative name2 Natriuretic Peptide, Pro, C-Type, aa30-50 (pro-CNP) Alternative name3 Natriuretic Peptide, Pro, C-Type, aa30- ... Alternative name4 Natriuretic Peptide, Pro, C-Type, aa30-50 Alternative name5 Anti -Natriuretic Peptide, Pro, C-Type, aa30-50 ( ... MBS621328 , Natriuretic Peptide, Pro, C-Type, aa30-50 (pro-CNP) Antibody size: 100ul , 1,149.25 USD Catalog number MBS621328 ...
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 ... type II (intermediate form), and type III (Kugelberg-Welander disease). Type I is fatal in infancy, type II has a late ... 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 ...
keywords = "Ca sensitization, Levosimendan, Myocardial stunning, ORM-3819, Phosphodiesterase III inhibition, Positive inotropic ... and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC50=3.88±0.3 nM) was revealed during in vitro ... and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC50=3.88±0.3 nM) was revealed during in vitro ... and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC50=3.88±0.3 nM) was revealed during in vitro ...
... a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev 19: 369-386. ... Sample mass has three types of uncertainty sources sensitivity, linearity, and repeatability. Mass of the sample was expressed ... quinolinone and is a quinolinone derivative that inhibits cellular phosphodiesterase III, and is used for the inhibition of ... J. PharmTech Res 3: 763-769.. *Jose K,Jaysekhar P, Jinu J (2014) HPTLC Determination of Cilostazol in Pharmaceutical Dosage ...
Cyclic nucleotide phosphodiesterases, specifically Type 5, break down cGMP to GMP by catalyzing a reaction that breaks the ... on the Relaxation of Human Corpus Cavernosum Tissue in Vitro and on the Activities of Cyclic Nucleotide Phosphodiesterase ... Carter, et al., "Effect of the Selective Phosphodiesterase Type Inhibitor Sildenafil on Erectile Function in the Anesthetized ... "Sildenafil, a Novel Inhibitor of Phosphodiesterase Type 5 in Human Corpus Cavernosum Smooth Muscle Cells", Life Sciences 62 ( ...
The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases ( ... Chitinase-3-like protein 1 protects skeletal muscle from TNFα-induced inflammation and insulin resistance Sven W. Görgens, ... Biochemical Journal May 01, 2014, 459 (3) 551-564; DOI: https://doi.org/10.1042/BJ20131363 ... Biochemical Journal May 01, 2014, 459 (3) 427-439; DOI: https://doi.org/10.1042/BJ20130172 ...
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 ...
1981) Effects of cyclic AMP- and cyclic GMP- phosphodiesterase inhibitors on immunological release of histamine and on lung ... nucleotide-phosphodiesterase as a possible mode of action of papaverine and similarly acting drugs. Naunyn Schmiedebergs Arch ... 1970) Cyclic phosphodiesterase activity and the action of papaverine. Biochem Biophys Res Commun 40:64-69. ... L-type voltage-operated calcium channel. PDE. phosphodiesterase receptor-operated calcium channels. ...
... 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 ... 8 (3): 182-193. doi:10.1038/nrn2093. PMC 1887812 . PMID 17311005. Burgoyne RD, OCallaghan DW, Hasdemir B, Haynes LP, Tepikin ...
... phosphodiesterase (CNPase) in the corpus callosum of the wild-type and Act1-deficient mice. As shown in Figure 1E, cuprizone ... cyclic nucleotide 3′- ... 4A) than wild-type controls. Cuprizone-induced PDGFR-α+ cell ... IL-17 is produced by varied cell types, including CD8+ T cells, γδT, and NK cells as well as CD4+ Th17 cells. Interestingly, we ... To determine the role of the IL-17A-Act1 axis in cuprizone-induced demyelination, we fed age- and sex-matched wild-type, IL-17A ...
In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and ... We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP ... 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and ... the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue. The ...
Identification of Interaction Sites of Cyclic Nucleotide Phosphodiesterase Type 3A with Milrinone and Cilostazol Using ... Genistein Inhibits Cardiac L-Type Ca2+ Channel Activity by a Tyrosine Kinase-Independent Mechanism Andriy E. Belevych, Sunita ... Vascular Smooth Muscle Cell Phosphodiesterase (PDE) 3 and PDE4 Activities and Levels are Regulated by Cyclic AMP in Vivo ... 2,3,7,8-Tetrachlorodibenzo-p-dioxin Suppresses Tumor Necrosis Factor-α and Anti-CD40-Induced Activation of NF-κB/Rel in ...
... cyclic monophosphate (cGMP) synthesis counters this response. Here, we show that blocking the intrinsic catabolism of c … ... Cyclic GMP / metabolism * Cyclic GMP-Dependent Protein Kinases * Cyclic Nucleotide Phosphodiesterases, Type 5 ... Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy Nat Med. 2005 Feb;11(2):214-22. ... Here, we show that blocking the intrinsic catabolism of cGMP with an oral phosphodiesterase-5A (PDE5A) inhibitor (sildenafil) ...
  • Tissue Cyclic-3',5'-adenosine monophosphate (cAMP) levels are determined by the balance between activities of the synthesizing enzyme and the catabolizing enzymes, such as the cyclic 3',5'-nucleotide phosphodiesterases (PDE) that hydrolyze the 3'-phosphoester bond of cAMP to its biologically inactive noncyclic nucleotides 5'-AMP [ 8 ]. (biomedcentral.com)
  • The 29 nucleotide (nt) insertion/deletion (indel) polymorphism is 2214 nts upstream from the PDE3A1 translation start site that regulates transcriptional activity in response to cyclic adenosine monophosphate (cAMP) levels, with the insertion (INS) allele having a frequency of 0.41. (yahoo.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 present study shows by computational analysis that the enzyme encoded by the E. coli cpdA gene belongs to a family of phosphodiesterases that closely resembles the catalytic machinery known from purple acid phosphatases and several other dimetallophosphoesterases. (nih.gov)
  • Furthermore, the known biochemical properties of the bacterial phosphodiesterase encoded by the cpdA gene, such as the requirement of iron ions and a reductant for maintaining its catalytic activity, support this hypothesis developed by computational analysis. (nih.gov)
  • Systematic search for single nucleotide polymorphisms in the 5' flanking region of the human phosphodiesterase 3B gene: absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes. (nih.gov)
  • Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. (wikipedia.org)
  • 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)
  • Prominent interferon (IFN) inducible gene signatures in TB patients and animal models of Mycobacterium tuberculosis infection have drawn significant attention to the roles of type I IFNs in the host response to mycobacterial infections. (frontiersin.org)
  • Recently described gene signatures in blood of patients with active TB disease ( 3 - 9 ) are being explored extensively for their utility as biomarkers for the reliable diagnosis of active TB, tracking of at-risk individuals, and monitoring of treatment outcome. (frontiersin.org)
  • Additionally, the discovery of IFN-related gene signatures in patients with active TB disease ( 3 - 9 ) has created significant momentum behind investigation of the innate immune pathways and pathophysiological consequences of type I IFN expression during M. tuberculosis infection. (frontiersin.org)
  • Association between a variation in the phosphodiesterase 4D gene and bone mineral density. (naver.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)
  • Development of decompensated dilated cardiomyopathy is associated with decreased gene expression and activity of the milrinone-sensitive cAMP phosphodiesterase PDE3A. (semanticscholar.org)
  • Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases. (semanticscholar.org)
  • Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K: A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. (drugbank.ca)
  • Piri N, Gao YQ, Danciger M, Mendoza E, Fishman GA, Farber DB: A substitution of G to C in the cone cGMP-phosphodiesterase gamma subunit gene found in a distinctive form of cone dystrophy. (hmdb.ca)
  • abstract = "This study is the first pharmacological characterization of the novel chemical entity, ORM-3819 (L-6-{4-[N'-(4-Hydroxi-3-methoxy-2-nitro-benzylidene)-hydrazino]-phenyl}-5-methyl-4,5-dihydro-2 H-pyridazin-3-one), focusing primarily on its cardiotonic effects. (elsevier.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)
  • Penile erection is caused through vascular pressure changes within the corpora cavernosa wherein the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway plays the key physiological mediator of erection. (spotidoc.com)
  • Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated vasorelaxation effector mechanisms in vascular smooth muscle. (onlinejacc.org)
  • The influx of Ca 2+ also stimulates Ca 2+ -calmodulin-dependent nitric-oxide (NO) synthase (NOS) type to produce NO, which stimulates guanylyl cyclase to produce cGMP (for review, see Garthwaite, 1991 ). (aspetjournals.org)
  • Most of the effects of the signaling molecule nitric oxide (NO) are mediated by cGMP, which is synthesized by soluble guanylyl cyclase and degraded by phosphodiesterases. (rupress.org)
  • Here we show that in platelets and aortic tissue, NO led to a biphasic response characterized by a tremendous increase in cGMP (up to 100-fold) in less than 30 s and a rapid decline, reflecting the tightly controlled balance of guanylyl cyclase and phosphodiesterase activities. (rupress.org)
  • Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. (diabetesjournals.org)
  • In this context, epidemiological evidence consistent with an increased risk of atherosclerosis in diabetes is mounting, with a possible role for 1 ) insulin resistance and its associated hyperinsulinemia, 2 ) poor glycemic control leading to elevated levels of advanced glycosylated end products, or 3 ) elevated circulating leptin levels associated with increased adipose mass ( 1 - 5 ). (diabetesjournals.org)
  • Here, we review recent developments in the understanding of the innate immune pathways that drive type I IFN responses in mycobacteria-infected host cells and the functional consequences for the host defense against M. tuberculosis , with a view that such insights might be exploited for the development of targeted host-directed immunotherapies and development of reliable biomarkers. (frontiersin.org)
  • Nitric oxide sustains long-term skeletal muscle regeneration by regulating fate of satellite cells via signaling pathways requiring Vangl2 and cyclic GMP. (optistem.org)
  • Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases. (ox.ac.uk)
  • Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. (biomedcentral.com)
  • Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment to a single oral dose of sildenafil 12.5, 25 or 50 mg or matching placebo. (onlinejacc.org)
  • Shal-related subfamily, member 3) voltage-gated potassium channels Nitric oxide synthase TRPC5 channel Ric8a Frq modulates Ca2+ entry through a functional interaction with the α1 voltage-gated Ca2+-channel subunit. (wikipedia.org)