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

Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells. (1/146)

The present study investigates the potential role of the Ca2+-calmodulin-dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell videoimaging. Vinpocetine (2.5-50 microM), a selective inhibitor of type I PDE, induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations in these pituitary cells, and at the same time produced an increase of the intracellular cGMP content. The cell permeable cGMP analog N2,2'-O-dibutyryl-cGMP (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823 (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor. Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage-sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic cGMP levels. Collectively, the results of the present study suggest that spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of type I PDE-cGMP-PKG pathway.  (+info)

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytes. (2/146)

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)

The calcium/calmodulin-dependent phosphodiesterase PDE1C down-regulates glucose-induced insulin secretion. (3/146)

To understand the role cAMP phosphodiesterases (PDEs) play in the regulation of insulin secretion, we analyzed cyclic nucleotide PDEs of a pancreatic beta-cell line and used family and isozyme-specific PDE inhibitors to identify the PDEs that counteract glucose-stimulated insulin secretion. We demonstrate the presence of soluble PDE1C, PDE4A and 4D, a cGMP-specific PDE, and of particulate PDE3, activities in betaTC3 insulinoma cells. Selective inhibition of PDE1C, but not of PDE4, augmented glucose-stimulated insulin secretion in a dose-dependent fashion thus demonstrating that PDE1C is the major PDE counteracting glucose-dependent insulin secretion from betaTC3 cells. In pancreatic islets, inhibition of both PDE1C and PDE3 augmented glucose-dependent insulin secretion. The PDE1C of betaTC3 cells is a novel isozyme possessing a K(m) of 0.47 microM for cAMP and 0.25 microM for cGMP. The PDE1C isozyme of betaTC3 cells is sensitive to 8-methoxymethyl isobutylmethylxanthine and zaprinast (IC(50) = 7.5 and 4.5 microM, respectively) and resistant to vinpocetine (IC(50) > 100 microM). Increased responsiveness of PDE1C activity to calcium/calmodulin is evident upon exposure of cells to glucose. Enhanced cAMP degradation by PDE1C, due to increases in its responsiveness to calcium/calmodulin and in intracellular calcium, constitutes a glucose-dependent feedback mechanism for the control of insulin secretion.  (+info)

Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell line BRIN-BD11. (4/146)

1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. 2. Calmodulin activated cyclic AMP or cyclic GMP PDE activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. 3. The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC(50) 1 - 5 microM), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. 4. The PDE3-selective inhibitors Org 9935 (0.02 - 10 microM) and siguazodan (0.1 - 10 microM) inhibited cyclic AMP PDE activity in the pellet but not the supernatant fractions of cell homogenates, with a maximum inhibition of about 30%. IGF-1 (2 - 7.5 ng ml(-1)) potently augmented this PDE activity. 5. RT - PCR using specific primers for PDE3B, but not for PDE3A, amplified, from BRIN - BD11 cell total RNA, a 351 base pair product that was >97% homologous with rat adipose tissue PDE3B. 6. IBMX, Org 9935, siguazodan and rolipram (1 - 50 microM), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. 7. These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion.  (+info)

Differential inhibition of multiple cAMP phosphodiesterase isozymes by isoflavones and tyrphostins. (5/146)

A series of isoflavone and tyrphostin compounds were found to inhibit the degradation of cAMP by several cyclic nucleotide phosphodiesterase (PDE) isozymes. Specific hydroxyl groups on the isoflavone structure were critical for PDE isozyme-selective inhibition. Replacement of the C-7 hydroxyl group of the isoflavone with a methoxy group raised the IC(50) for PDE1, PDE3, and PDE4. The absence of the C-5 hydroxyl group raised the IC(50) from 5 to >100 microM for PDE4, but actually lowered the IC(50) for PDE3 and PDE1. Replacement of the C-4' hydroxyl group with a methoxy group raised the IC(50) for PDE3 and PDE1, yet only slightly changed the IC(50) for PDE4. Various tyrphostins were also potent inhibitors of PDE1, PDE3, and PDE4. The four-carbon side chained tyrphostins were much less potent; however, a very interesting pattern was observed in which removal of phenolic hydroxyls on the tyrphostin structure increased the potency for PDE1 and PDE3, but not PDE4. These results may help to explain some of the therapeutic and intracellular signaling effects of isoflavones and tyrphostins. Moreover, the isozyme selectivity demonstrated by the isoflavones and tyrphostins can serve as a pharmacophore for the design of specific PDE inhibitors.  (+info)

Differential changes in the expression of cyclic nucleotide phosphodiesterase isoforms in rat brains by chronic treatment with electroconvulsive shock. (6/146)

Electroconvulsive shock (ECS) has been suggested to affect cAMP signaling pathways to exert therapeutic effects. ECS was recently reported to increase the expression of PDE4 isoforms in rat brain, however, these studies were limited to PDE4 family in the cerebral cortex and hippocampus. Thus, for comprehensive understanding of how ECS regulates PDE activity, the present study was performed to determine whether chronic ECS treatment induces differential changes in the expression of all the PDE isoforms in rat brains. We analyzed the mRNA expression of PDE isoforms in the rat hippocampus and striatum using reverse transcription polymerase chain reaction. We found chronic ECS treatment induced differential changes in the expression of PDE isoform 1, 2, 3, 4, 5 and 7 at the rat hippocampus and striatum. In the hippocampus, the expression of PDE1A/B (694%), PDE4A (158%), PDE4B (323 %), and PDE4D (181%) isoforms was increased from the controls, but the expression of PDE2 (62.8%) and PDE7 (37.8%) decreased by chronic ECS treatment. In the striatum, the expression of PDE1A/B (179%), PDE4A (223%), PDE4B (171%), and PDE4D (327%) was increased by chronic ECS treatment with the concomitant decrease in the expression of PDE2 (78.4%) and PDE3A (67.1%). In conclusion, chronic ECS treatment induces differential changes in the expression of most PDE isoforms including PDE1, PDE2, PDE3, PDE4, PDE5, and PDE7 in the rat hippocampus and striatum in an isoform- and brain region-specific manner. Such differential change is suggested to play an important role in regulation of the activity of PDE and cAMP system by ECS.  (+info)

"cAMP-specific" phosphodiesterase contributes to cGMP degradation in cerebellar cells exposed to nitric oxide. (7/146)

Nitric oxide (NO) functions as a diffusible messenger in the central nervous system and elsewhere, exerting many of it physiological effects by activating soluble guanylyl cyclase, so increasing cellular cGMP levels. Hydrolysis of cyclic nucleotides is achieved by phosphodiesterases (PDEs) but the enzyme isoforms responsible for degrading cGMP in most cells have not been identified. We have devised a method for quantitatively monitoring the rate of breakdown of cGMP within intact cells and have applied it to rat cerebellar cell suspensions previously stimulated with NO. In contrast to previous findings in cultured cerebellar cells, there was no evidence from the use of selective inhibitors that PDE 1 participated importantly in cGMP hydrolysis. Moreover, procedures expected to increase PDE 1 activity by raising cytosolic Ca2+ concentrations (neurotransmitter agonists, Ca2+ ionophore) failed to influence cGMP breakdown. Instead, through the use of inhibitors selective for different PDE families, two isoforms were implicated: a "cGMP-specific" PDE (PDE 5), inhibited by sildenafil and zaprinast, and a "cAMP-specific" PDE (PDE 4), inhibited by low concentrations of rolipram and Ro-20-1724 and by milrinone. An explanation is offered for a participation of PDE 4 based on the high estimated intracellular cGMP concentration (approximately 800 microM) and the low affinity of the enzyme for cGMP. In accordance with predictions, recombinant PDE 4 was shown to hydrolyze high cGMP concentrations in a rolipram-sensitive manner. The widespread use of rolipram to test for a specific involvement of cAMP in cellular phenomena must therefore be questioned.  (+info)

Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. (8/146)

From a series of benzamide derivatives, roflumilast (3-cyclo-propylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) was identified as a potent and selective PDE4 inhibitor. It inhibits PDE4 activity from human neutrophils with an IC(50) of 0.8 nM without affecting PDE1 (bovine brain), PDE2 (rat heart), and PDE3 and PDE5 (human platelets) even at 10,000-fold higher concentrations. Roflumilast is almost equipotent to its major metabolite formed in vivo (roflumilast N-oxide) and piclamilast (RP 73401), however, more than 100-fold more potent than rolipram and Ariflo (cilomilast; SB 207499). The anti-inflammatory and immunomodulatory potential of roflumilast and the reference compounds was investigated in various human leukocytes using cell-specific responses: neutrophils [N-formyl-methyl-leucyl-phenylalanine (fMLP)-induced formation of LTB(4) and reactive oxygen species (ROS)], eosinophils (fMLP- and C5a-induced ROS formation), monocytes, monocyte-derived macrophages, and dendritic cells (lipopolysaccharide-induced tumor necrosis factor-alpha synthesis), and CD4+ T cells (anti-CD3/anti-CD28 monoclonal antibody-stimulated proliferation, IL-2, IL-4, IL-5, and interferon-gamma release). Independent of the cell type and the response investigated, the corresponding IC values (for half-maximum inhibition) of roflumilast were within a narrow range (2-21 nM), very similar to roflumilast N-oxide (3-40 nM) and piclamilast (2-13 nM). In contrast, cilomilast (40-3000 nM) and rolipram (10-600 nM) showed greater differences with the highest potency for neutrophils. Compared with neutrophils and eosinophils, representing the terminal inflammatory effector cells, the relative potency of roflumilast and its N-oxide for monocytes, CD4+ T cells, and dendritic cells is substantially higher compared with cilomilast and rolipram, probably reflecting an improved immunomodulatory potential. The efficacy of roflumilast in vitro and in vivo (see accompanying article in this issue) suggests that roflumilast will be useful in the treatment of chronic inflammatory disorders such as asthma and chronic obstructive pulmonary disease.  (+info)

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 ...
The 2020 Gordon Research Seminar on Cyclic Nucleotide Phosphodiesterases (GRS) will be held in Les Diablerets, Switzerland. Apply today to reserve your spot.
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 ...
Adenosine, Magnesium, Kinase, Protein Kinase, Mitosis, Memory, Learning, Mice, Brain, Hippocampus, Bone, Bone Marrow, Cell, and Cell Cycle
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General Research Interests: Regulation and function of cyclic nucleotide phosphodiesterases in the cardiovascular system. Second messenger cyclic nucleotides (cAMP and cGMP) regulate many signaling pathways in the cardiovascular system. For example, the vascular tone, smooth muscle cell growth, and cardiac muscle contractility are all regulated by cyclic nucleotide signaling. We are interested in phosphodiesterases (PDEs), the enzymes that break down cyclic nucleotides and thus control the amplitude, duration, and compartmentalization of cyclic nucleotide signaling in the cell. It has become increasingly clear that cyclic nucleotide degradation by PDEs is not a constitutive function of the cell, but rather a highly regulated one controlled by different mechanisms in different physiological and pathological circumstances. PDE regulation and function is further complicated by the fact that there are more than 50 individual PDEs belonging to 11 different PDE families, yet our understanding of the ...
General Research Interests: Regulation and function of cyclic nucleotide phosphodiesterases in the cardiovascular system. Second messenger cyclic nucleotides (cAMP and cGMP) regulate many signaling pathways in the cardiovascular system. For example, the vascular tone, smooth muscle cell growth, and cardiac muscle contractility are all regulated by cyclic nucleotide signaling. We are interested in phosphodiesterases (PDEs), the enzymes that break down cyclic nucleotides and thus control the amplitude, duration, and compartmentalization of cyclic nucleotide signaling in the cell. It has become increasingly clear that cyclic nucleotide degradation by PDEs is not a constitutive function of the cell, but rather a highly regulated one controlled by different mechanisms in different physiological and pathological circumstances. PDE regulation and function is further complicated by the fact that there are more than 50 individual PDEs belonging to 11 different PDE families, yet our understanding of the ...
Direct interactions between Ca2+ and cAMP have provided the basis for models predicting their interdependent oscillations in excitable cells (Cooper et al., 1995; Gorbunova and Spitzer, 2002; Rapp and Berridge, 1977; Yu et al., 2004). Central to all of these models are the actions of Ca2+ on Ca2+-inhibited and Ca2+-stimulated ACs respectively. Other key features include the feedback of cAMP onto Ca2+ channels and Ca2+/calmodulin-dependent PDE activity. Evidence of a dynamic interplay between Ca2+ and cAMP as a consequence of Ca2+-dependent PDE activity (PDE1C) was presented in a recent paper by Landa and colleagues (Landa et al., 2005). In this report, we reveal that cAMP oscillations can arise in non-excitable cells lacking both VGCCs and Ca2+-stimulated PDE activity. Artificially imposed or CCh-induced Ca2+ oscillations were shown to generate simple oscillations in cAMP matching the Ca2+ oscillation frequency. These oscillations were due to the stimulation of a Ca2+-sensitive AC (AC8), and ...
87% Improvement in Cognitive Function. Researchers have been eager to determine whether vinpocetine has any value in memory enhancement. The answer is a definitive yes. In an Italian study of 22 elderly patients suffering from central nervous system degenerative disorders, 87 percent experienced improvement in cognitive function after taking 10 mg of vinpocetine daily for 30 days, followed by 5 mg three times daily for 60 days. No significant side effects were noted.. …While many studies focus on the effects of vinpocetine for patients suffering from various degenerative conditions, researchers have also inquired into the effects of this agent in healthy individuals. In a German study, 40 healthy volunteers were given 40 mg of vinpocetine daily for two days. This brief course resulted in a significant improvement in memory as assessed by the Sternberg Memory Scanning Test. This study suggests that in normal, healthy people, vinpocetine can enhance memory quickly.. Vinpocetine may not be a ...
Vinpocetine, chemically known as ethyl apovincaminate, is a vinca alkaloid that exhibits cerebral blood-flow enhancing and neuroprotective effects.
Vinpocetine, chemically known as ethyl apovincaminate, is a vinca alkaloid that exhibits cerebral blood-flow enhancing and neuroprotective effects.
Understand the usages of Vinpocetine in various health conditions. Explore other smart treatment options, see research evidence, and find out about peoples experiences with many popular treatments, including feedback from patients and professionals.
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, ...
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
The hydrolysis of cyclic nucleotide second messengers takes place through multiple cyclic nucleotide phosphodiesterases (PDEs). The significance of this diversification is not fully understood. Here we report the differential regulation of low K(m) Ca2+-activated (PDE1C) and Ca2+-independent, rolipr …
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 ...
This session is open to all educators and administrators who are conducting program evaluation in schools such as quality assurance officers, evaluation personnel, program chairpersons, principals and assistant principals, counselors, psyshometricians, and teachers. ​. Objectives of the Session:. 1. Conceptualize evaluation for programs offered in ones institution. 2. Construct evaluation tools appropriate for evaluation framework selected. Topics and Schedule:. 8:00-12:00 Program Evaluation Models. 1:00-4:00 Workshop. ​. Registration. The registration fee for the CPDP is Php 1,500.00,which includes conference materials and snacks. Registrants can pay through bank with this account: Name of Account: PHILIPPINE EDUCATIONAL MEASUREMENT AND EVALUATION ASSOCIATION. Account Number: 004103-0466-32. Bank: Bank of the Philippine Islands (BPI). Branch Address: Masangkay-Mayhaligue. To acknowledge payment, please scan bank deposit receipt with the participants full name, school, and cell phone ...
Vinpocetine is an excellent anti-oxident, helping both memory and improving blood circulation. Thinkbetteruk provide only the purist Vinpocetine.
The planned experimentation has 2 major goals: to define the biological importance and operational mechanism of a non-second messenger, cyclic nucleotide (CN) m...
Source Naturals Vinpocetine may improve cognitive performance and short-term memory loss that is sometimes experienced with stress or aging.
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 ...
Chlamydomonas reinhardtii contains a factor that can replace adenosine 3:5-cyclic monophosphate (cAMP) in the stimulation of rabbit-muscle protein kinase. The factor cochromatographs and coelectrophoreses with authentic cAMP, and is inactivated by beef heart cyclic nucleotide phosphodiesterase. When C. reinhardtii is exposed to aminophylline (theophylline(2) ethylenediamine), the concentration of the factor in the cells increases within 1 hr, from about 25 pmol of cAMP equivalents per g dry weight to more than 250 pmol. Cyclic nucleotide phosphodiesterase activity is present in crude extract of C. reinhardtii and is inhibited by theophylline. We conclude that cAMP occurs in C. reinhardtii and that the endogenous concentration is governed at least in part by a theophylline-sensitive cyclic nucleotide phosphodiesterase. These findings provide a sound basis for attributing the effects of methylxanthines on flagellar function and regeneration in C. reinhardtii to the resultant elevation of endogenous cAMP
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 ...
Sinha, P K. and Prasad, K N., A further study on the regulation of cyclic nucleotide phosphodiesterase activity in neuroblastoma cells. Effect of growth. (1977). Subject Strain Bibliography 1977. 1280 ...
Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome ...
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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 ...
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 ...
This article describes a novel staircase-like decanuclear copper(ii) cluster [CuII10(cpdp)4(CO3)4(CH3OH)2]·3.33CH3OH·7.83H2O (1) (H3cpdp = N,N′-bis[2-carboxybenzomethyl]-N,N′-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol) composed of a pair of [CuII5] pentamers. In methanol, the reaction of H3cpdp with Cu(NO3)
Vinpocetine is a compound from the Periwinkle plant that is used as a cognitive protective and anti-aging agent. One of the more common of the nootropics, Vinpocetine may enhance blood flow and is touted to increase memory; this latter claim has not been investigated.
Vinpocetine is a semisynthetic byproduct of the active alkaloid in the Periwinkle plant. It is a well-known neuroprotective anti-aging compound.
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 ability to respond to light is crucial for most organisms. BLUF is a recently identified photoreceptor protein domain that senses blue light using a FAD chromophore. BLUF domains are present in various proteins from the Bacteria, Euglenozoa and Fungi. Although structures of single-domain BLUF proteins have been determined, none are available for a BLUF protein containing a functional output domain; the mechanism of light activation in this new class of photoreceptors has thus remained poorly understood. Here we report the biochemical, structural and mechanistic characterization of a full-length, active photoreceptor, BlrP1 (also known as KPN_01598), from Klebsiella pneumoniae. BlrP1 consists of a BLUF sensor domain and a phosphodiesterase EAL output domain which hydrolyses cyclic dimeric GMP (c-di-GMP). This ubiquitous second messenger controls motility, biofilm formation, virulence and antibiotic resistance in the Bacteria. Crystal structures of BlrP1 complexed with its substrate and metal ...
Since cAMP blocks meiotic maturation of mammalian and amphibian oocytes in vitro and cyclic nucleotide phosphodiesterase 3A (PDE3A) is primarily responsible for oocyte cAMP hydrolysis, we generated PDE3A-deficient mice by homologous recombination. The Pde3a-/- females were viable and ovulated a normal number of oocytes but were completely infertile, because ovulated oocytes were arrested at the germinal vesicle stage and, therefore, could not be fertilized. Pde3a-/- oocytes lacked cAMP-specific PDE activity, contained increased cAMP levels, and failed to undergo spontaneous maturation in vitro (up to 48 hours). Meiotic maturation in Pde3a-/- oocytes was restored by inhibiting protein kinase A (PKA) with adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS) or by injection of protein kinase inhibitor peptide (PKI) or mRNA coding for phosphatase CDC25, which confirms that increased cAMP-PKA signaling is responsible for the meiotic blockade. Pde3a-/- oocytes that underwent germinal ...
The market research report provides a detailed analysis and data about the Vinpocetine market statistical study, the key players, growth dynamics, and geographical analysis. The report provides the information concerning the factors that impel the growth of the Vinpocetine global industry. The Vinpocetine market constitute of the leading groups which play a vital role in the product sales, manufacturing, production, distribution of the products in order to meet the supply and demand chain. A detailed study of the global market share of the past and the future along with the predictable forecast trends is also mentioned in the present report.. Read Complete Report with TOC : www.mrsresearchgroup.com/market-analysis/global-and-chinese-vinpocetine-market-2015-industry-trends.html. Purview of the Global Vinpocetine Report :. • The report mentions the essential information regarding the global Vinpocetine market along with segmentation, statistical, and geographical data ...
Chlorpromazine, Hydrochloride - CAS 69-09-0 - Calbiochem Inhibits calmodulin-dependent stimulation of cyclic nucleotide phosphodiesterase (IC₅₀ = 17 µM). - Find MSDS or SDS, a COA, data sheets and more information.
A sensitive, versatile and economical method to extract and quantify cyclic nucleotide monophosphates (cNMPs) using LC-MS/MS, including both 3,5-cNMPs and 2,3-cNMPs, in mammalian tissues and cellular systems has been developed. Problems, such as matrix effects from complex biological samples, are addressed and have been optimized. This protocol allows for comparison of multiple cNMPs in the same system and was used to examine the relationship between tissue levels of cNMPs in a panel of rat organs. In addition, the study reports the first identification and quantification of 2,3-cIMP. The developed method will allow for quantification of cNMPs levels in cells and tissues with varying disease states, which will provide insight into the role(s) and interplay of cNMP signalling pathways.
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In an adult, cerebral blood flow is typically 750 millilitres per minute or 15% of the cardiac output. Vinpocetine enhances cerebral blood flow by dilating blood vessels and reducing blood viscosity. Vinpocetine enhances cerebral metabolism by helping to maintain healthy blood flow and oxygen utilization. ...
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].
0123] Adamantidis A R, Zhang F, Aravanis A M, Deisseroth K and de Lecea L. 2007. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450, 420-424 [0124] Airan R D, Thompson K R, Fenno L E, Bernstein H, Deisseroth K. 2009. Temporally precise in vivo control of intracellular signaling. Nature 458, 1025 1029 [0125] Barends, T. R. M., E. Hartmann, J. Griese, N. V. Kirienko, D. A. Ryjenkov, J. Reinstem, R. L. Shoeman, M. Gomelsky, I. Schlichting. 2009. Structure and mechanism of a light-regulated cyclic nucleotide phosphodiesterase. Nature 459, 1015-1018 [0126] Bhoo, S-H, Davis, S J, Walker, J., Karniol B, Vierstra R. 2001. Bacteriophytochromes are photochromic histidine kinases using a biliverdin chromophore, Nature 414, 776-779 [0127] Bulina M E, Chudakov D M, Britanova O V, Yanushevich Y G, Staroverov D B, Chepurnykh T V, Merzlyak E M, Shkrob M A, Lukyanov S, Lukyanov K A. 2006 A genetically encoded photosensitizer. Nat Biotechnol 24, 95-9 [0128] Bruder, ...
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
THE CYCLIC NUCLEOTIDES, CAMP AND CGMP ARE IMPORTANT REGULATORY MOLECULES THAT ARE NOW RECOGNIZED AS MEDIATORS IN A VAST NUMBER OF NORMAL AND PATHOLOGICAL PROCESSES. SUCH INSIGHTS HAVE INCREASED THE NEED FOR GENERALLY AVAILABLE TECHNOLOGY THAT WILL ALLOW THE CONVENIENT AND ACCURATE MEASUREMENT OF THE CYCLIC NUCLEOTIDES IN RESEARCH AND CLINICAL SETTINGS. THIS PHASE I PROPOSAL OUTLINES OUR INTEREST IN PURSUING THE GENERATION OF MURINE MONOCLONAL ANTI CAMP/CGMP ANTIBODIES AND FLUORESCENT ENZYME IMMUNOASSAY SYSTEMS FOR THE RAPID AND SENSITIVE MEASUREMENT OF THE CYCLIC NUCLEOTIDES IN BIOLOGICAL MATERIALS. HYBRIDOMAS WILL BE PREPARED VIA FUSION OF MOUSE MYELOMA CELLS WITH SPLEENS OF MICE IMMUNIZED WITH SUCCINYL-CAMP (OR CGMP) CONJUGATED TO BOVINE SERUM ALBUMIN. RESULTANT MONOCLONAL ANTIBODIES WILL BE ATTACHED TO BETA-GALACTOSIDASE AND UTILIZED IN A RAPID SOLID-PHASE ENZYME IMMUNOASSAY USING FLUOROGENIC SUBSTRATES. THESE EXPECTED RESULTS WILL SERVE AS THE BASIS OF PHASE II, WHERE WE ENVISION THAT THE ...
studies on the Cyclic AMP-Phosphodiesterases and other aspects of the aggregation of Dictyostelium discoideum by Charles John McDonald Membrane bound cyclic AMP phosphodiesterase (mPDE) is prematurely induced by cyclic nucleotides during early development of D.discoideum. Factors affecting this induction were studied, including transcriptional inhibitors and an inhibitor of cyclic AMP dependant protein kinases (indomethacin). Amoebae secrete a form of PDE (SPDE) which was chosen as a molecular marker for the induction due to its ease of purification. In preparations free of the protein inhibitor (PDE-I) multiple forms (A, B and C) of sPDE were studied. sPDE-A was purified to homogeneity by column chromatography and consists of one subunit, P50. Antibody, raised against pure sPDE-A, immunoprecipitated all three forms of sPDE. sPDE-B was correlated with equimolar amounts of p50 and p52 and is a dimer. sPDE-C was correlated with P52 and p50 in an approximate 2/l ratio and is thus probably a trimer. ...
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 ...
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.
In an adult, cerebral blood flow is typically 750 millilitres per minute or 15% of the cardiac output. Vinpocetine enhances cerebral blood flow by dilating blood vessels and reducing blood viscosity. Vinpocetine enhances cerebral metabolism by helping to maintain healthy blood flow and oxygen utilization.Vinpocetine is derived from vincamine, the major indole alkaloid of the periwinkle plant. No toxic effects have been seen from vinpocetine use at levels far above those recommended for this product.When taken orally, vinpocetine is easily absorbed and it can:Improve blood supply to the brainIncrease oxygen and glucose use by the brainMaintain optimal energy of healthy brainsMaintain normal coagulation of bloodMaintain healthy levels of some neurotransmittersPromote healthy attention, memory and concentrationExerts an inhibitory effect on NF-kB-dependent inflammationServing size is 10mg. We have 10mg micro scoops available for purchase.
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.
This trial compared treprostinil with other FDA approved therapies (including: epoprostenol; treprostinil; type-5 cyclic nucleotide phosphodiesterase
Vinpocetine, a derivative of the alkaloid vincamine, has been clinically used in many countries for treatment of cerebrovascular disorders such as stroke and dementia for more than 30 years. Currently, vinpocetine is also available in the market as a dietary supplement to enhance cognition and memory. Due to its excellent safety profile, increasing efforts have been put into exploring the novel therapeutic effects and mechanism of actions of vinpocetine in various cell types and disease models. Recent studies have revealed a number of novel functions of vinpocetine, including anti-inflammation, antagonizing injury-induced vascular remodeling and high-fat-diet-induced atherosclerosis, as well as attenuating pathological cardiac remodeling ...
Recent report from National Toxicology Program found consumption of vinpocetine was associated with adverse reproductive effects in animals.
The Global and Chinese Vinpocetine Industry, 2012-2022 Market Research Report is a professional and in-depth study on the current state of the global Vin
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 ...
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DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
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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 ...
... cyclic nucleotide phosphodiesterases ARF1 (ADP Ribosylation factor 1) A type (Kv4.3; Shal-related subfamily, member 3) voltage- ... type III phosphatidylinositol 4-kinase β) IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment ... came from the assumption that the protein was expressed only in neuronal cell types, which is not the case. GRCh38: Ensembl ... NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins. NCS-1 ...
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 ... DMSO induced P19 cells to aggregate and process mesodermal and endodermal cell types. The cellular mechanism that occurs during ... 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; ...
It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine ... "The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I ... Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5'-pApA (phosphadenylyl adenosine). pApA is also ... "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9 ...
"Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... Fertel R, Weiss B (July 1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" ( ... cGMP-specific phosphodiesterase type 5 is an enzyme (EC 3.1.4.17) from the phosphodiesterase class. It is found in various ... Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ...
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 ...
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 ( ... Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ...
1998). "Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: ... "Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential ... High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene. The ... "Entrez Gene: PDE9A phosphodiesterase 9A". Verhoest PR, Fonseca KR, Hou X, et al. (2012). "Design and discovery of 6-[(3S,4S)-4- ...
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 ... 28 (1): 1-17. doi:10.1002/jnr.490280102. PMID 1710279. Eylar EH, Brostoff S, Hashim G, Caccam J, Burnett P (September 1971). " ... 6 (1): 16-22. doi:10.1016/0888-7543(90)90443-X. PMID 1689270. Kishimoto A, Nishiyama K, Nakanishi H, et al. (1985). "Studies on ...
2003). "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in ... 2003). "Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ ... cyclic nucleotide phosphodiesterase". Biochem Biophys Res Commun. 250 (3): 751-6. doi:10.1006/bbrc.1998.9379. PMID 9784418. " ... High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by ...
September 2003). "Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system ... PDE3A can be either membrane-associated or cytosolic, depending on the variant and the cell type it is expressed in. PDE3A and ... Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... WO 03012030, Movsesian M, "Isoform-Selective Inhibitors and Activators of PDE3 Cyclic Nucleotide Phosphodiesterases", published ...
"Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... Journal of Cyclic Nucleotide Research. 2 (3): 139-48. PMID 6493. Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless ... "Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded ...
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 ...
Sun L, Wu J, Du F, Chen X, Chen ZJ (February 2013). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type ... 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 ...
"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". Molecular Pharmacology. 48 (1): 121-30 ...
2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi:10.1067/mai ... Jan 2012). "Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental ... Fertel R, Weiss B (1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". Mol. ... Weiss B (1975). "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv. ...
"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor". British Journal of ... A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action ... Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998). "Rolipram, a type IV-specific phosphodiesterase inhibitor, ... Dinter, H (February 2000). "Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?". BioDrugs. ...
"Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell.[9]. ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488-520. doi:10.1124/pr. ...
... cyclic-nucleotide phosphodiesterase MeSH D08.811.277.352.640.160 - 2',3'-cyclic-nucleotide phosphodiesterases MeSH D08.811. ... myosin type iii MeSH D08.811.277.040.025.525.843 - myosin type iv MeSH D08.811.277.040.025.525.875 - myosin type v MeSH D08.811 ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 - cyclic amp-dependent protein kinases ... myosin type i MeSH D08.811.277.040.025.525.750 - myosin type ii MeSH D08.811.277.040.025.525.750.124 - cardiac myosins MeSH ...
White matter Schwann cells 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase) List of human cell types derived from the germ ... Oligodendrocytes are a type of glial cell. They arise during development from oligodendrocyte precursor cells (OPCs), which can ... They are the last cell type to be generated in the CNS. Oligodendrocytes were discovered by Pío del Río Hortega. ... Oligodendrocytes (from Greek 'cells with a few branches'), or oligodendroglia, are a type of neuroglia whose main functions are ...
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 ...
This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the ... The fourth type - filiform papillae do not contain taste buds). Beyond the papillae, taste receptors are also in the palate and ... The HCN channels were such a proposal; as they are cyclic nucleotide-gated channels. The two ion channels now suggested to ... taste+receptors,+type+1 at the US National Library of Medicine Medical Subject Headings (MeSH) taste+receptors,+type+2 at the ...
He is best known for his work with cyclic nucleotide phosphodiesterases. He was the first to propose, based on his experimental ... He showed that a single cell type may contain more than one form of phosphodiesterase [6,7] and that different forms of ... one on the potential therapeutic application of cyclic nucleotides: (Weiss, Benjamin, ed., Cyclic Nucleotides in Disease[1]), ... Cyclic Nucleotide Phosphodiesterases: Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated ...
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 ... 53 (1): 49-54. doi:10.1111/j.1439-0442.2006.00786.x. PMID 16411910. Lantz RC, Chen GJ, Solyom AM, Jolad SD, Timmermann BN (June ...
In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 ... The GAF domain is a type of protein domain that is found in a wide range of proteins from all species. The GAF domain is named ... a ubiquitous signaling motif and a new class of cyclic GMP receptor". The EMBO Journal. 19 (20): 5288-99. doi:10.1093/emboj/ ... "The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding". Proceedings of the ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... Paraxanthine is a phosphodiesterase type 9 (PDE9) inhibitor and it is sold as a research molecule for this same purpose. ... Paraxanthine is a selective inhibitor of cGMP-preferring phosphodiesterase (PDE9) activity and is hypothesized to increase ... Paraxanthine is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits ...
Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... "Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality". Heart. 102 ( ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... McMahon, C. G.; McMahon, C. N.; Leow, L. J. & Winestock, C. G. (2006). "Efficacy of type-5 phosphodiesterase inhibitors in the ...
"Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling". ... Phosphodiesterase enzymes have been shown to be different in different types of cells, including normal and leukemic ... Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases" (PDF). The Journal of Allergy and Clinical Immunology. 108 ( ... Caffeine content in coffee varies widely depending on the type of coffee bean and the method of preparation used; even beans ... Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor. As a competitive nonselective phosphodiesterase ... One meta analysis has found that caffeine consumption is associated with a reduced risk of type 2 diabetes. Two meta analyses ...
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. ...
... resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of ... A third type of light-sensing cell, the photosensitive ganglion cell, is important for entrainment of circadian rhythms and ... This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, ... There are two types of centre-surround structures in the retina - on-centres and off-centres. On-centres have a positively ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... LIPE, AOMS4, FPLD6, HSL, LHS, lipase E, hormone sensitive type. External IDs. OMIM: 151750 MGI: 96790 HomoloGene: 3912 ... which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs protein- ... 273 (1): 215-21. doi:10.1074/jbc.273.1.215. PMID 9417067.. *. Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB (1999). "Interaction ...
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 ... "Characterization of cyclic nucleotide phosphodiesterase isoforms associated to isolated cardiac nuclei". Biochim. Biophys. Acta ... "Identification of the cpdA gene encoding cyclic 3′,5′-adenosine monophosphate phosphodiesterase in Escherichia coli". J. Biol. ...
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.[5] ... type 1 angiotensin receptor binding. • protein complex binding. • signal transducer activity. • protein binding. • GTPase ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... retina development in camera-type eye. • Ras protein signal transduction. • cell proliferation. • cellular response to hypoxia ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... The third type of glucose 6-phosphatase deficiency, glucose 6-phosphatase-β deficiency, is characterized by a congenital ... 1993). "Glycogen Storage Disease Type I". PMID 20301489.. Cite journal requires ,journal=. (help). ... Chou JY, Matern D, Mansfield BC, Chen YT (March 2002). "Type I glycogen storage diseases: disorders of the glucose-6- ...
3 Types of G protein signaling *3.1 Heterotrimeric G proteins *3.1.1 Common mechanism *3.1.1.1 Activation ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ...
... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... guanyl-nucleotide exchange factor activity. • RNA binding. Cellular component. • cytoplasm. • ciliary basal body. • centrosome ... "Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: paucity of mutations in the coding ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... It is suggested that 57 enzymes fall into the type I category whereas the rest fall into the type II group, including the ... and there are two classifications of these enzymes including type I and type II. ... Other types of PET degrading hydrolases have been known before this discovery.[2] These include hydrolases such as: lipases, ...
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was ... Involved in growth and metastasis of some types of tumors.[24]. *Used in the endocrine system for peptide and amino-acid ... When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide ... These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates ...
... which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation causes extremely high ... Types[edit]. There are membrane-bound (type 1, guanylate cyclase-coupled receptor) and soluble (type 2, soluble guanylate ... Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on ... Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the ...
"Differential Activation and Inhibition of the Multiple Forms of Cyclic Nucleotide Phosphodiesterase". Advances in Cyclic ... is a drug used to block the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth ... Weiss, B; Hait, W N (1977). "Selective Cyclic Nucleotide Phosphodiesterase Inhibitors as Potential Therapeutic Agents". Annual ... Fertel, Richard; Weiss, Benjamin (1976). "Properties and Drug Responsiveness of Cyclic Nucleotide Phosphodiesterases of Rat ...
Yeast tRNA cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3' end. Yeast tRNA ... exon then performs a nucleophilic attack at the first nucleotide following the last nucleotide of the intron at the 3' splice ... This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts for more than 99% of splicing. ... Splicing occurs in all the kingdoms or domains of life, however, the extent and types of splicing can be very different between ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ...
Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. CiteSeerX 10.1.1.319. ... cAMP phosphodiesterase converts cAMP into AMP by breaking the phosphodiester bond, in turn reducing the cAMP levels ... which vary based on the type of cell. ... cyclic nucleotide-gated ion channels[9]. *exchange proteins ... caffeine and theophylline inhibit cAMP phosphodiesterase, which degrades cAMP - thus enabling higher levels of cAMP than would ...
This compound is a potent inhibitor of cGMP specific phosphodiesterase type 5, the enzyme that degrades the signalling molecule ... This block of nucleotide biosynthesis is more toxic to rapidly growing cells than non-dividing cells, since a rapidly growing ... cyclic guanosine monophosphate.[40] This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... 1. 1. −. [. I. ]. [. I. ]. +. K. i. =. V. max. −. V. max. [. I. ]. [. I. ]. +. K. i. {\displaystyle {\cfrac {V_{\max }}{\cfrac ...
The cyclic AMP-regulatory dimers are degraded by phosphodiesterase and release 5'AMP. DNA in the cell nucleus binds to ... G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • activation of adenylate cyclase ... LHCGR have been found in many types of extragonadal tissues, and the physiologic role of some has remained largely unexplored. ... Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was ...
Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3 ... This α-subunit then activates a phosphodiesterase that catalyzes the conversion of cGMP to GMP, thereby reducing current ... though in some cases the truncated proteins may be able to coassemble with wild-type channels in a dominant negative fashion. ... There are at least four genetic causes of congenital ACHM, two of which involve cyclic nucleotide-gated ion channels (ACHM2/ ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Phosphodiesterase type 11 (PDE11) is a type of phosphodiesterase enzyme. An inhibitor is BC11-38. ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... "Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth ... For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to ... Phospholipase C, gamma 1, also known as PLCG1, is a protein that in humans is encoded by the PLCG1 gene.[5][6] ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... 1994). "New type of linkage between a carbohydrate and a protein: C-glycosylation of a specific tryptophan residue in human ...
... acts as a phosphodiesterase (PDE) type-1 inhibitor in isolated rabbit aorta,[12] Independent of vinpocetine's ... Hagiwara M, Endo T, Hidaka H (February 1984). "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle ... "Vinpocetine for cognitive impairment and dementia". The Cochrane Database of Systematic Reviews (1): CD003119. doi:10.1002/ ... 1] an extract from the lesser periwinkle plant. Vinpocetine was first isolated from the plant in 1975 by the Hungarian chemist ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... 1 p22.3. Deoxyribonuclease II (EC 3.1.22.1, DNase II, pancreatic DNase II, deoxyribonucleate 3'-nucleotidohydrolase, pancreatic ... DNase II alpha (usually known as DNase II), which is thought to be ubiquitously expressed in human tissue[1] ...
Single-nucleotide polymorphisms (SNPs) in the P2RX7 receptor gene are associated with an increased risk of bone fracture. The ... There are two types of NTs: Concentrative nucleoside transporters (CNTs): Na+-dependent symporters Equilibrative nucleoside ... the ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and alkaline phosphatases (APs). Extracellular AMP is hydrolyzed ... for sustained platelet aggregation through the inhibition of adenylate cyclase and a corresponding decrease in cyclic adenosine ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... Protein serine/threonine phosphatase (PSP)[1] is a form of phosphoprotein phosphatase that acts upon phosphorylated serine/ ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Type II[edit]. Type II site-specific deoxyribonuclease. Structure of the homodimeric restriction enzyme EcoRI (cyan and green ... Type V[edit]. Type V restriction enzymes (e.g., the cas9-gRNA complex from CRISPRs[43]) utilize guide RNAs to target specific ... Type l[edit]. Type I restriction enzymes were the first to be identified and were first identified in two different strains (K- ...
... cGMP in turn activates cyclic nucleotide-dependent protein kinase G, which phosphorylates various proteins that play a role in ... Here is a list of examples of the nitrate type (in alphabetical order): Acesaniamide[citation needed] Diethylene glycol ... PDE5 inhibitors block deactivation of cGMP by the enzyme phosphodiesterase-5. In combination with the increased cGMP production ... Guanylate cyclase produces cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). ...
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 ...
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 ...
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 ...
Calcium/calmodulin dependent 3 5 cyclic nucleotide Phosphodiesterase 1B. *Calcium/calmodulin stimulated cyclic nucleotide ... Phosphodiesterase 1B calmodulin dependent. *Presumed 63kDa form of the type 1 cyclic nucleotide phosphodiesterase family known ... Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ... By product type. Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex ...
Cyclic Nucleotide Phosphodiesterases, Type 1. *Gene Expression Profiling/methods. *Gene Expression Regulation, Developmental ... Wild-type (Crl:CD1(ICR)) female x Hemizygous Tg male littermate or reciprocal mating ... Wild-type (C57BL/6J) female x Hemizygous Tg male or reciprocal mating ... 1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The ...
... determine the factors required for the activity of these compounds and also for the selectivity versus other phosphodiesterase ... and benzothienothiadiazines derivatives as phosphodiesterase 7 inhibitors has been carried out in order to ... 3,5-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors* * Cyclic Nucleotide Phosphodiesterases, Type 7 ... A CoMFA study of benzo- and benzothienothiadiazines derivatives as phosphodiesterase 7 inhibitors has been carried out in order ...
Inhibition of sperm phosphodiesterase (PDE) has been shown to increase cAMP concentrations and stimulate motility and the ... 3,5-Cyclic-AMP Phosphodiesterases * Cyclic Nucleotide Phosphodiesterases, Type 1 * Cyclic Nucleotide Phosphodiesterases, Type ... Enhancement of motility and acrosome reaction in human spermatozoa: differential activation by type-specific phosphodiesterase ... Using type-selective inhibitors, we identified two of the PDE forms expressed in human spermatozoa and studied their ...
Identification of Interaction Sites of Cyclic Nucleotide Phosphodiesterase Type 3A with Milrinone and Cilostazol Using ... Identification of Interaction Sites of Cyclic Nucleotide Phosphodiesterase Type 3A with Milrinone and Cilostazol Using ... Identification of Interaction Sites of Cyclic Nucleotide Phosphodiesterase Type 3A with Milrinone and Cilostazol Using ... Identification of Interaction Sites of Cyclic Nucleotide Phosphodiesterase Type 3A with Milrinone and Cilostazol Using ...
... cyclic nucleotide phosphodiesterases ARF1 (ADP Ribosylation factor 1) A type (Kv4.3; Shal-related subfamily, member 3) voltage- ... type III phosphatidylinositol 4-kinase β) IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment ... came from the assumption that the protein was expressed only in neuronal cell types, which is not the case. GRCh38: Ensembl ... NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins. NCS-1 ...
... type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative colitis via down-regulation of iNOS and ... Advances in targeting cyclic nucleotide phosphodiesterases. Maurice, D.H.; Ke, H.; Ahmad, F. ... Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative... El-Ashmawy, Nahla E.; Khedr ... Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative colitis via down-regulation of ...
... cyclic AMP, cyclic nucleotide phosphodiesterases, type 1, glucose, humans, insulin, insulin-like growth factor I, islets of ... Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin ... Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin ... The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized ...
... of type I and type II cyclic-AMP-dependent protein kinases by using cyclic nucleotide analogs. Eur. J. Biochem. 181, 19- 31. ... phosphodiesterases (PDE) (2), and guanine nucleotide exchange factors (Epac) (3) bind cAMP. Interestingly, localized pools of ... both of which are required for cyclic nucleotide discrimination.. Recently the affinities of a range of widely used cyclic ... Bradley, J., Reisert, J., and Frings, S. (2005 ) Regulation of cyclic nucleotide-gated channels. Curr. Opin. Neurobiol. 15, 343 ...
Fusion of an ASKHA Phosphotransferase and a Cyclic Nucleotide Phosphodiesterase Homolog. Structure. 14, 1263-1272. ... Kahl, C. A., Marsh, J., Fyffe, J., Sanders, D. A., and Cornetta, K. (2004). Human immunodeficiency virus type 1-derived ... Human immunodeficiency virus type 1 vectors with alphavirus envelope glycoproteins produced from stable packaging cells. J ... Cell Growth Differ 1, 251-258.. Sanders, D. A., Gillece-Castro, B. L., Stock, A. M., Burlingame, A. L., and Koshland, D. E., Jr ...
... such as cyclic nucleotide phosphodiesterases and protein tyrosine phosphatases. Zinc signals are crucial for regulation of ... whereas they downregulate the production of type-1 interferons and nitric monoxide. Another project has shown that Interleukin- ... Secretariat TIB 4/3-1. Gustav-Meyer-Allee 25. 13355 Berlin. Germany ...
2′,3′- Cyclic nucleotide 3′-phosphodiesterase Rn.31762 3163 373 8.5 Cdh2 Cadherin 2, type 1, N-cadherin (neuronal) Rn.17239 ... Gut NCSCs are self-renewing and multipotent, give rise to diverse types of neurons and glia in vivo, and persist in the gut ... 1. Flow-cytometric analysis of Ret, and CD29 (β1 integrin) expression by E14.5 gut p75+α4+ NCSCs and E14.5 gut p75-α4- ... and endothelin receptor type B (EDNRB)(12) (Tables 1 and 2). ... Endothelin receptor type B Rn.11412 1159 117 9.9 Cart Cocaine ...
More recently, we analyzed the bronchoalveolar lavage of CF and wild-type mice for cell infiltrates and expression of pro- ... More recently, we analyzed the bronchoalveolar lavage of CF and wild-type mice for cell infiltrates and expression of pro- ... Using phosphodiesterase type 5 (PDE5) inhibitors, we and others have provided evidence of rescued F508del-CFTR trafficking and ... Using phosphodiesterase type 5 (PDE5) inhibitors, we and others have provided evidence of rescued F508del-CFTR trafficking and ...
Intracellular cyclic nucleotide levels increase in response to extracellular stimulation by hormones, neurotransmitters, or ... Cyclic nucleotide phosphodiesterases (PDEs) constitute a family of enzymes that degrade cAMP and cGMP. ... Cyclic Nucleotide Phosphodiesterases, Type 1 Actions. * Search in PubMed * Search in MeSH ... Cyclic nucleotide phosphodiesterases (PDEs) constitute a family of enzymes that degrade cAMP and cGMP. Intracellular cyclic ...
The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases ( ... Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias.. Molina CE, Leroy J, Richter W, ... Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular ... Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia. ...
The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent ... The type strain of C. flosculorum is UFMG-JL13(T) (=CBS 10566(T)=NRRL Y-48258(T)) and the type strain of C. floris is UWO(PS) ... The resolution of acute inflammation induced by cyclic AMP is dependent on annexin A1. J Biol Chem. 2017;292:13758-13773 pubmed ... The complete sequencing and annotation of the genome of the type strain C. fetus subsp. venerealis NCTC 10354(T) are reported ...
Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of ... Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of ... Kakkar, R., Raju, R. V. S., and Sharma, R. K. (1999). Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1). Cell. ... Beavo, J. A. (1995). Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol. Rev. 75, 725- ...
Cyclic nucleotide phosphodiesterases, specifically Type 5, break down cGMP to GMP by catalyzing a reaction that breaks the ... that inhibit Phosphodiesterase type 5 (PDE5) or otherwise inhibit degradation of guanosine 3′,5′-cyclic monophosphate (a.k.a., ... 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 ...
Reduced nitric oxide - cyclic guanosine monophosphate (cGMP) signaling is observed in age-related vascular disease. We ... Human genetic studies revealed significant associations of PDE1A single nucleotide polymorphisms with diastolic blood pressure ... to wild-type (WT) levels. PDE1C levels were increased in lung and aorta. cGMP hydrolysis by PDE in lungs was higher in Ercc1d/- ... Phosphodiesterase 1 regulation is a key mechanism in vascular aging. Paula Katherina Bautista Nino, Matej Durik, A.H. Jan ...
Cyclic Nucleotide Phosphodiesterases, Type 4; K676NL63N7 / Rolipram ... Semantic-Type. And with semantic types: A. Entity. A1. Physical Object. A1.1. Organism. A1.1.1. Archaeon. A1.1.2. Bacterium. ... Publication-Type. And with publication types: Clinical Trial. Editorial. Letter. Meta-Analysis. Practice Guideline. Randomized ... include both record types include both record types but rank higher the records having abstract (the default BML behavior) + ...
3,5-Cyclic-AMP Phosphodiesterases [D08.811.277.352.640.150]. *Cyclic Nucleotide Phosphodiesterases, Type 3 [D08.811.277.352. ... "Cyclic Nucleotide Phosphodiesterases, Type 3" by people in UAMS Profiles by year, and whether "Cyclic Nucleotide ... Cyclic Nucleotide Phosphodiesterases, Type 2. *Cyclic Nucleotide Phosphodiesterases, Type 3. *Cyclic Nucleotide ... "Cyclic Nucleotide Phosphodiesterases, Type 3" is a descriptor in the National Library of Medicines controlled vocabulary ...
Inhibition of type 4 cyclic nucleotide phosphodiesterase blocks intracellular TLR signaling in chronic lymphocytic leukemia and ... Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006;58(3):488-520. ... Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014;13(4):290-314. ... 3 The therapeutic utility of controlling the intracellular levels of cyclic-AMP, and of cyclic guanosine monophosphate (cyclic- ...
... cyclic nucleotide phosphodiesterase; K-ATP, ATP-sensitive potassium channel; VDCC, voltage-dependent calcium channel; NSCC, non ... The role of L-type and N-type Voltage-Dependent Calcium Channels as determinants of neuropeptide secretion was first ... High-throughput FRET assays for fast time-dependent detection of cyclic AMP in pancreatic beta cells. "Cyclic Nucleotide ... Chapter 3, Cyclic Nucleotide Signaling, 2015. This review describes the details of a novel FRET-based assay for use in the ...
"Type II glucocorticoid receptors are expressed in oligodendrocytes and astrocytes, Journal of Neuroscience Research" on ... Immunocytochemical localization by electron microscopy of 2′,3′ ‐cyclic nucleotide 3′‐phosphodiesterase in developing ... In the brain, two types of high‐affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II ... In the brain, two types of high‐affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II ...
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis. Abstract Baillie, George S. University of Glasgow ... Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. Abstract Parent, Carole A. ... Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters. Abstract ... Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation. Abstract ...
... and cGMP analogues on transcriptional activity and replication of human immunodeficiency virus type 1 (HIV-1) was investigated ... Transfection of PKG1β expression plasmid increased expression from an HIV-1 LTR-reporter as well as from an infectious HIV-1 ... These findings provide evidence that cGMP and PKG serve to regulate HIV-1 infection in human cells. ... cyclic GMP) dependent protein kinase 1-β (PKG1-β) ... molecular clone, pNL4-3. Treatment of HIV-1 AD8-infected ...
Protein concentrations were determined by Bradford assay (Bio-Rad), and cAMP levels were measured using the Cyclic Nucleotide ... Experiments shown in panel E and F were performed in the presence of the phosphodiesterase inhibitor R0-20-1724 (25 μmol/L). ... L-type, and P/Q-type Ca2+ currents (27). Thus, ADORA1 can inhibit exocytosis of glucagon-containing granules in α-cells, and ... Prophylactic insulin treatment in relatives at high risk for type 1 diabetes. Diabetes Metab Rev 1993;9:289-293pmid:7924826. ...
  • 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. (strath.ac.uk)
  • Cyclic nucleotide phosphodiesterases (PDEs) constitute a family of enzymes that degrade cAMP and cGMP. (cdc.gov)
  • Intracellular cyclic nucleotide levels increase in response to extracellular stimulation by hormones, neurotransmitters, or growth factors and are down-regulated through hydrolysis catalyzed by PDEs, which are therefore candidate therapeutic targets. (cdc.gov)
  • Some PDEs such as type 4 are specific for cAMP, while others such PDE5, specific for cGMP ( Beavo, 1995 ). (frontiersin.org)
  • However, each of the main kinetoplastid parasites express four class 1-type cyclic nucleotide-specific phosphodiesterases (PDEA-D), which have highly similar catalytic domains to that of human PDEs. (gla.ac.uk)
  • 1 The synthesis and degradation of cyclic-AMP are tightly controlled by 2 classes of enzymes, adenylyl cyclases and phosphodiesterases (PDEs), respectively. (bloodjournal.org)
  • 2,3 Cyclic GMP is degraded by cGMP-hydrolyzing phosphodiesterases (PDEs). (ahajournals.org)
  • 6 Like NO, cGMP can affect multiple signaling pathways ( Figure 1 A). 1,5,6 To date, three classes of cGMP receptor proteins have been identified: cyclic nucleotide-gated (CNG) cation channels, cGMP-regulated PDEs, which hydrolyze cAMP and/or cGMP, and cGMP-dependent protein kinases (cGKs). (ahajournals.org)
  • 8 These and other studies 9,10 also underlined the importance of cAMP phosphodiesterases (PDEs) for the spatiotemporal control of cAMP signals. (ahajournals.org)
  • This project aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs) in the fight for neglected parasitic diseases (NPD). (europa.eu)
  • cGMP-driven activation of protein kinases, ion channels, or phosphodiesterases (PDEs) causes a broad variety of physiological responses whereas dysregulation can result in severe pathologies. (springer.com)
  • Intracellular cAMP concentration is regulated by the activities of at least two families of enzymes: adenylyl and guanylyl cyclases, responsible for cAMP and cGMP synthesis and cyclic nucleotide phosphodiesterases (PDEs) that mediate cAMP and cGMP hydrolysis.Among the PDE superfamily, PDE2 is a dual substrate enzyme that hydrolyzes both cAMP and cGMP and has the unique property to be stimulated by cGMP. (worldcat.org)
  • A-kinase anchoring proteins (AKAPs) and cyclic nucleotide phosphodiesterases (PDEs) are essential enzymes in the cyclic adenosine 3'-5' monophosphate (cAMP) signaling cascade. (mdpi.com)
  • The level of intracellular cAMP is controlled through its production by adenylyl cyclases and its breakdown by cyclic nucleotide phosphodiesterases (PDEs). (lu.se)
  • Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the amplitude and duration of cAMP and cGMP signaling by controlling cyclic nucleotide (cNT) degradation. (pnas.org)
  • cAMP is the intracellular messenger for LH action on steroidogenesis, and pharmacological evidence indicates that the response to LH can be modulated by cyclic nucleotide phosphodiesterases (PDEs). (pnas.org)
  • However the types and roles of the PDEs present in Leydig cells have not been fully defined. (pnas.org)
  • In Leydig cells from wild-type mice, 3-isobutyl-1-methylxanthine, a compound that inhibits all cAMP PDEs except PDE8A, elicited only a small increase in the sensitivity of testosterone production to LH. (pnas.org)
  • cAMP signaling pathways are controlled through regulation of the synthesis of cAMP by adenylyl cyclases and degradation by phosphodiesterases (PDEs) ( 1 , 2 ). (pnas.org)
  • The cyclic nucleotide-PDEs are now recognized to form a superfamily of 11 different, but homologous, gene-families that all contain highly homologous catalytic domains near their C termini ( 3 ). (pnas.org)
  • Several other proteins such as cyclic nucleotide gated ion channels ( 1 ), phosphodiesterases (PDE) ( 2 ), and guanine nucleotide exchange factors (Epac) ( 3 ) bind cAMP. (mcponline.org)
  • Several neuronal markers such as neurofilament proteins, HNK-1 antigen and tetanus toxin binding sites are expressed at highest levels during these days. (wikipedia.org)
  • Expression of FLAG-tagged transfected PKG1β (top panel) and HIV-1 viral proteins are shown by Western blotting. (biomedcentral.com)
  • Viral proteins expressed from the HIV-1 molecular clone were then measured. (biomedcentral.com)
  • c-di-AMP is a signaling nucleotide used in signaling pathways that trigger outputs by using receptor or target proteins to sense c-di-AMP concentrations in the cell. (wikipedia.org)
  • At high concentrations, cyclic di-AMP binds to receptor and target proteins to control specific pathways. (wikipedia.org)
  • The second messenger 3′,5′-cyclic adenosine monophosphate (cyclic-AMP) uses effector proteins to influence cell function and fate. (bloodjournal.org)
  • Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs), such as the photoreceptor RHO. (uniprot.org)
  • Using wild type (wt) and non-myristoylated mutant PKG II proteins it was demonstrated that N-myristoylation (N-myr) is important for targeting of PKG II to membranes and distal ends of filopodia like structures in COS-1 and HEK-293 cells. (ubc.ca)
  • Recent research has focused mainly on the cyclic GMP pathway and phosphodiesterase type 5 (PDE5, cyclic GMP specific PDE) in the control of vaginal vascular smooth muscle, whereas only little is known on the role of other key proteins and mediators of cyclic nucleotide mediated signaling in this process. (elsevier.com)
  • EPAC is a cAMP-activated guanine nucleotide exchange factor (cAMP-GEF) for the small GTP-binding proteins Rap1 and Rap2. (pubmedcentralcanada.ca)
  • Heterotrimeric guanine nucleotide-binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins. (vwr.com)
  • None of the three universal stress proteins or nitroreductase, and a considerably lower amount of HspX was detected in carbon-starved wild-type cultures. (asm.org)
  • A tBLASTn search of the Myxococcus xanthus genome database at The Institute for Genomic Research (TIGR) identified three genes ( pdeA , pdeB , and pdeC ) that encode proteins homologous to 3′,5′-cyclic nucleotide phosphodiesterase. (asm.org)
  • Phosphodiesterase are enzymes that catalyze the hydrolysis of the 3′ cyclic phosphate bonds of adenosine and/or guanosine 3′, 5′ cyclic monophosphate ( Beavo, 1995 ). (frontiersin.org)
  • Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5'-pApA (phosphadenylyl adenosine). (wikipedia.org)
  • Since cyclic di-AMP is a signaling nucleotide, it is presumed to adhere to the same regulation pathways, where environmental changes are sensed by synthesis or degradation enzymes, which modulate enzyme concentration. (wikipedia.org)
  • Biochemical characterization of the inhibition of the two major phosphodiesterase isoenzymes in Drosophila by theophylline predicts only a slight inhibition of these enzymes in vivo , in accordance with the unchanged level of cAMP in wild-type fly heads during drug feeding. (springer.com)
  • 1] Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases: a diverse family of regulatory enzymes. (axonmedchem.com)
  • A number of diseases, including autosomal dominant hypertension with brachydactyly (HTNB) and type I long-QT syndrome (LQT1), result from mutations in genes encoding for distinct members of the two classes of enzymes. (mdpi.com)
  • The enzymes responsible for cGMP catabolism are the cyclic nucleotide phosphodiesterases, which catalyze the hydrolysis of cGMP and cAMP to the corresponding 5′-nucleotide monophosphate. (aspetjournals.org)
  • Some biochemical properties of these CaM mutants were also described such as their differential phosphorylation by the tyrosine kinase c-Src, and their action as compared to wild type, on the activity of two CaM-dependent enzymes: cyclic nucleotide phosphodiesterase 1 (PDE1) and endothelial nitric oxide synthase (eNOS) assayed in vitro. (dynano.eu)
  • Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. (nih.gov)
  • Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria and archaea. (wikipedia.org)
  • It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine pentaphosphate ((p)ppGpp), and cyclic di-GMP (c-di-GMP). (wikipedia.org)
  • Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3′,5′-cyclic adenosine monophosphate in lymphocytes. (bloodjournal.org)
  • 1 The most common and versatile second messenger, cyclic adenosine monophosphate (cAMP), regulates a striking number of physiological and pathophysiological processes through the signaling networks which interfere with many disease states including inflammatory disorders, immune-deficiencies, and cancer. (pubmedcentralcanada.ca)
  • Our earliest understanding of phosphodiesterase (PDE) inhibitors began with a series of publications by Sutherland and Rall in the 1950s, describing the properties of cyclic adenosine monophosphate (cAMP). (beds.ac.uk)
  • Reduced nitric oxide - cyclic guanosine monophosphate (cGMP) signaling is observed in age-related vascular disease. (clinsci.org)
  • 2 , 3 The therapeutic utility of controlling the intracellular levels of cyclic-AMP, and of cyclic guanosine monophosphate (cyclic-GMP), with PDE inhibitors is well established. (bloodjournal.org)
  • Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. (springer.com)
  • Transducin is a guanine nucleotide-binding protein found specifically in rod outer segments, where it mediates activation by rhodopsin of a cyclic GTP-specific (guanosine monophosphate) phosphodiesterase. (vwr.com)
  • 3. The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC(50) 1 - 5 microM), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. (strath.ac.uk)
  • Using phosphodiesterase type 5 (PDE5) inhibitors, we and others have provided evidence of rescued F508del-CFTR trafficking and corrected deficient chloride transport activity. (frontiersin.org)
  • Manish, B. 3D QSAR, pharmacophore indentification studies on series of 1-(2-ethoxyethyl)-1H-pyrazolo[4,3-d] pyrimidines as PDE5 inhibitors. (eurekaselect.com)
  • Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. (embl.de)
  • Inhibition of cGMP-specific phosphodiesterase type V (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. (embl.de)
  • Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of neuronal plasticity-related genes, neurotrophic factors, and neuroprotective molecules. (frontiersin.org)
  • The aim of the present study was to evaluate in the human vagina, by means of immunohistochemistry, the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in relation to calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and protein gene product 9.5 (PGP 9.5). (elsevier.com)
  • Conclusion: Key mediators of the cyclic AMP and cyclic GMP pathways are co-localized in nerves seen in close proximity to vascular smooth muscle expressing PDE1. (elsevier.com)
  • Using a combination of electrophysiological and optical imaging techniques, we show here that vinpocetine, a PDE type I inhibitor, restores ocular dominance plasticity in the ferret model of fetal alcohol exposure. (jneurosci.org)
  • Here, we try to restore ocular dominance plasticity in alcohol-exposed ferrets using the PDE type 1 inhibitor vinpocetine. (jneurosci.org)
  • Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative. (deepdyve.com)
  • El-Adawy, Samar A. 2018-03-01 00:00:00 BackgroundRoflumilast (Rof), a phosphodiesterase 4 (PDE4) inhibitor, has been shown to be an effective agent in inflammatory diseases and marketed for chronic obstructive pulmonary disease. (deepdyve.com)
  • Here, we show that the expression of a potential glucagon inhibitor, the adenosine A1 receptor (Adora1), is gradually diminished in α-cells of NOD mice, autoantibody-positive (AA + ) and overtly type 1 diabetic (T1D) patients during the progression of disease. (diabetesjournals.org)
  • Here, we review a decade-long exploration of the contribution of cyclic-AMP and PDE4 to the pathogenesis of B-cell lymphoma, 5 ⇓ ⇓ ⇓ - 9 culminating with the first-in-cancer clinical trial of a PDE4 inhibitor in advanced B-cell malignancies. (bloodjournal.org)
  • Luo, H.B. Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure. (eurekaselect.com)
  • The effects of a novel Ca(2+)-sensitizer (EMD 60263, 10 microM, group 1) were compared with a phosphodiesterase (PDE) III-inhibitor (enoximon, 20 microM, group 2) on 14 isolated, blood-perfused rabbit hearts during reperfusion after a global ischemia of 20 min. (curehunter.com)
  • Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. (tudelft.nl)
  • Since five other lipoxygenase inhibitors, a phospholipase inhibitor, an inhibitor of leukotriene formation and dexamethasone had no effect on the endotoxin-induced increase in PAI-1 synthesis, the effect of BW755C could not be ascribed to its known pharmacological properties. (tudelft.nl)
  • In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or N(G)-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. (tudelft.nl)
  • Since the activity of the cyclic nucleotide is also regulated by phosphodiesterase 5, we have examined the effect of zaprinast, an inhibitor of the enzyme, on the sheep isolated internal anal sphincter. (bmj.com)
  • Short-term or long-term treatments with a phosphodiesterase-4 (PDE4) inhibitor result in opposing agonist-induced Ca 2+ responses in endothelial cells. (unistra.fr)
  • The cGMP PDE inhibitor zaprinast (1 mg/kg) selectively reversed the blunted CVP response to GTN in tolerant animals but had no effect on the CVP response to GTN in nontolerant animals or on the MAP response in either group. (aspetjournals.org)
  • A large and diverse molecular repertoire shared by immune and CNS, such as cytokines, chemokines, the metalloproteinase/inhibitor, and Fas/Fas ligand systems, revealing remarkable similarities between signaling molecules and cellular receptors in both systems, could participate in this cross talk ( 1 ). (jimmunol.org)
  • Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. (abcam.com)
  • By the 1960s, the role of cyclic nucleotide second messengers, such as cAMP, in cell signaling and homeostasis was established, and regulation of this pathway by PDE inhibitors arose as a field of considerable interest. (beds.ac.uk)
  • Cyclic AMP (cAMP) and cyclic GMP (cGMP) are critical second messengers for the regulation of cardiac function. (worldcat.org)
  • Focuses on the role of cyclic nucleotide phosphodiesterase 10A (PDE10A) in regulating cardiac hypertrophy and dysfunction. (rochester.edu)
  • Focuses on the role of cyclic nucleotide phosphodiesterase 1C in smooth muscle cell remodeling in human vessel diseases. (rochester.edu)
  • 2. Calmodulin activated cyclic AMP or cyclic GMP PDE activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. (strath.ac.uk)
  • An enzyme that catalyzes the hydrolysis of cyclic AMP to form adenosine 5'-phosphate. (termsciences.fr)
  • Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia. (nih.gov)
  • 6 Mechanistically, PDE4 inhibition resulted in elevation of intracellular cyclic-AMP levels and suppression of PI3K and AKT activity. (bloodjournal.org)
  • 6 These data linked the cyclic-AMP/PDE4 axis to the essential tonic BCR signals, highlighting the potential impact of PDE4 modulation in malignant B cells ( Figure 1 ). (bloodjournal.org)
  • Inhibition of PDE4 (with 10 μmol/L Ro 20-1724) increased the amplitude and dramatically slowed down the onset and recovery of cAMP signals, whereas PDE3 blockade (with 1 μmol/L cilostamide) had a minor effect only on subsarcolemmal cAMP. (ahajournals.org)
  • Furthermore, this increase in cGMP degradation is paralleled by the phosphorylation of phosphodiesterase type 5 at Ser-92. (rupress.org)
  • The degradation of cAMP is achieved by 3′,5′-cyclic nucleotide phosphodiesterases, which catalyze cleavage of 3′,5′-cAMP to 5′-cAMP. (asm.org)
  • PDE-catalyzed cyclic nucleotide degradation provides an important mechanism for regulating signaling. (pnas.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)
  • Neurogenic relaxation of the internal anal sphincter is mediated by elevation of cyclic GMP, following activation of soluble guanylyl cyclase by nitric oxide. (bmj.com)
  • Increases in intracellular cAMP lead to activation of cAMP-dependent protein kinases, guanine nucleotide exchange factors, and cyclic nucleotide-gated channels, which in turn can regulate the activity of other signaling and metabolic pathways ( 1 ). (pnas.org)
  • We demonstrated that two receptor-type adenylyl cyclases (CyaA and CyaB) of M. xanthus act as osmosensors. (asm.org)
  • To study the effect of beta 1 subunit of the Na,K- ATPase in regulating tight junction and barrier function in acute lung injury in vivo. (rochester.edu)
  • Two C-terminal cyclic nucleotide binding (CNB) domains cooperatively bind two molecules of cAMP, resulting in a conformational change of the R subunit that releases the active catalytic kinase subunit(s) from the inhibitory pseudo-substrate or substrate site of PKAR. (nature.com)
  • Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and olfactory signal transduction. (uniprot.org)
  • Activates both type 1 and type 2 PKA and binds to the cAMP binding site 2 on the regulatory subunit of PKA. (emdmillipore.com)
  • A potent, non-degradable, cell-permeable analog of cAMP that binds to the cAMP binding site 2 on the protein kinase A (PKA) regulatory subunit and activates both type I and II PKA. (emdmillipore.com)
  • Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also exhibits expression of a calcium-sensitive cAMP/cGMP phosphodiesterase 1C (PDE1C) and the vasopressin type 2 receptor. (forskningsdatabasen.dk)
  • Taking advantage of the large growth cone size of cultured primary neurons from pond snail Lymnaea stagnalis combined with dsRNA knockdown, we show that neuronal calcium sensor-1 (NCS-1) regulates neurite extension and branching, and activity-dependent Ca 2+ signals in growth cones. (biologists.org)
  • however, published receptor binding data also support the potential L-type voltage- operated calcium channel (L-VOCC) blocking effect of drotaverine. (aspetjournals.org)
  • The overall aim is to measure zinc signals and understand their function in the respective signal transduction pathways, and they were even able to identify molecular targets for zinc signals, such as cyclic nucleotide phosphodiesterases and protein tyrosine phosphatases. (uni-potsdam.de)
  • Although stem cell properties have been characterized in many tissues ( 1 ), we are only beginning to understand how stem cell function is regulated at the molecular level. (sciencemag.org)
  • Transfection of PKG1β expression plasmid increased expression from an HIV-1 LTR-reporter as well as from an infectious HIV-1 molecular clone, pNL4-3. (biomedcentral.com)
  • B) Co-transfection of PKG1β and HIV-1 infectious molecular clone, pNL4-3, resulted in dose dependent increase in viral protein expression. (biomedcentral.com)
  • This collaborative study using computational molecular modeling and FRET-based assays for cAMP revealed the promiscuous nature of glucagon and GLP-1 receptor agonist and antagonist action at family B GPCRs. (upstate.edu)
  • When, concurrently, oncologists began examining the mechanisms of oncogenesis in higher eukaryotes using the same molecular biology techniques as their cell cycle counterparts, it was revealed that many cancer cells have defective G 1 checkpoint mechanisms and that cancer cells depend on G 2 checkpoint far more than normal cells ( 4 , 5 ). (aacrjournals.org)
  • The Haase team could show that they are fine tuning signaling by Toll-like receptor 4, promoting the secretion of pro-inflammatory cytokines, whereas they downregulate the production of type-1 interferons and nitric monoxide. (uni-potsdam.de)
  • In the brain, two types of high‐affinity receptors bind glucocorticoids, the type I, mineralocorticoid receptor and the type II, glucocorticoid receptor (GR). Both receptor types are expressed by many types of neurons. (deepdyve.com)
  • This study reveals that the GLP-1 receptor agonist Exendin-4 can be conjugated to vitamin B12 so that its bioavailability favors a glucoregulatory effect at the pancreas rather than a C.N.S. mediated effect to induce nausea. (upstate.edu)
  • This study was a collaboration with the laboratory of Dr. Robert N. Cooney of the Department of Surgery at SUNY Upstate in which the Holz laboratory participated in the discovery that the a7 nicotinic acetylcholine receptor is a pentameric cation channel that mediates stimulatory effects of GTS-21 on enteroendocrine L-cell GLP-1 release. (upstate.edu)
  • Modeling Analysis of Inositol 1,4,5-Trisphosphate Receptor-Mediated Ca2+ Mobilization Under The Control Of Glucagon-Like Peptide-1 In Mouse Pancreatic Beta-Cells. (upstate.edu)
  • 8-Phenyltheophylline, an adenosine receptor antagonist in mammals, slightly retards memory decay in the wild-type. (springer.com)
  • We found that mice deficient in IL-17A, IL-17 receptor C (IL-17RC), and adaptor protein Act1 (of IL-17R) all had reduced demyelination accompanied by lessened microglial and polydendrocyte cellular reactivity compared with that in wild-type mice in response to cuprizone feeding, demonstrating the essential role of IL-17-induced Act1-mediated signaling in cuprizone-induced demyelination. (jneurosci.org)
  • 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. (elsevier.com)
  • The phenotype was the opposite of that of the receptor-type adenylyl cyclase ( cyaA or cyaB ) mutant. (asm.org)
  • The novel GLP-1/GIP dual receptor agonist DA3-CH is neuroprotective in the pilocarpine-induced epileptogenesis rat model. (annals.org)
  • In bacteria, cyclic di-AMP has been implicated in the control of growth, cell wall homeostasis, bacterial biofilm formation and virulence gene expression, heat and osmotic stress regulation and responses, sporulation, potassium transport, lysis, and antibiotic resistance. (wikipedia.org)
  • Cyclic di-AMP has also been linked to bacterial RNA synthesis inhibition. (wikipedia.org)
  • During the past three decades, a huge number of studies have reported that Human immunodeficiency virus type-1 (HIV-1) destroys the function of different cells in the blood that are involved in fighting bacterial, viral and fungal infections. (uab.edu)
  • Therefore, these cells are not able to fight HIV-1 or other bacterial infections in HIV patients. (uab.edu)
  • The enzyme is widely distributed in animal tissue and controls the level of intracellular cyclic AMP. (termsciences.fr)
  • Intracellular cyclic AMP (cAMP) levels of pdeA or pdeB mutant cells under these stressful conditions were about 1.3-fold to 2.0-fold higher than those of wild-type cells. (asm.org)
  • One of the main objectives of this work was to investigate whether substances other than caffeine in coffee may influence the homeostasis of intracellular cyclic nucleotides in vitro and in vivo. (uni-kl.de)
  • The nucleotide either binds to the helicase DDX41, which in turn activates the STING pathway, or directly binds to the STING protein. (wikipedia.org)
  • Cyclic di-AMP has been identified (along with 2'3'-cGAMP) as a ligand that induces closing of the STING dimer, leading to STING polymerization and pathway activation. (wikipedia.org)
  • Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease. (mayo.edu)
  • Cyclic nucleotide phosphodiesterase To elucidate the regulatory pathway of DNA replication by light, we studied the effect of several inhibitors, including two electron transport inhibitors, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), on DNA replication in S. elongatus 7942. (vegfrsignaling.com)
  • They are essential regulators of cyclic nucleotide signaling with diverse physiological functions. (axonmedchem.com)
  • Cyclic di-AMP has been linked to fatty acid synthesis regulation in Myobacterium smegmatis, the growth of S. aureus in conditions of low potassium, the sensing of DNA integrity in B. subtilis, and cell wall homeostasis in multiple species. (wikipedia.org)
  • It is suggested that cyclic di-AMP is involved in the regulation of cell lysis. (wikipedia.org)
  • However, there has been no study to examine if and how NCS-1 is involved in regulation of the window level of Ca 2+ permissive to neurite outgrowth. (biologists.org)
  • Metalloproteinase PAPP-A regulation of IGF-1 contributes to polycystic kidney disease pathogenesis. (mayo.edu)
  • To determine whether the regulation of PDE3B gene expression is correlated with fat cell size, we examined this gene expression in adipose tissues of IRS-1 (-/-) mice. (elsevier.com)
  • Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine- phosphorylated caveolin‑1. (unistra.fr)
  • Inhibition of phosphodiesterase (PDE) 1 and 5 normalized SNPrelaxing effects in Ercc1 d/- to wild-type (WT) levels. (clinsci.org)
  • Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance. (semanticscholar.org)
  • Cyclic di-AMP synthesis is inhibited by the GImM I154F mutation in the lactococcus lactis bacterium. (wikipedia.org)
  • Synthesis is regulated a number of ways, including negative feedback inhibition and upregulation through a decrease in phosphodiesterase. (wikipedia.org)
  • Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis. (semanticscholar.org)
  • Overall, the data showed that the induction of PAI-1 synthesis by endotoxin in vivo can be up- and down-regulated pharmacologically, but the mechanisms involved remain elusive. (tudelft.nl)
  • A CoMFA study of benzo- and benzothienothiadiazines derivatives as phosphodiesterase 7 inhibitors has been carried out in order to determine the factors required for the activity of these compounds and also for the selectivity versus other phosphodiesterase isoenzymes. (nih.gov)
  • This methodology is employed to gain clues on the design of new fused thiadiazines with improved activity and selectivity on phosphodiesterase 7. (nih.gov)
  • Using the information achieved from the three CoMFA models, new structures have been designed in silico and their inhibitory activity on phosphodiesterase 7 was predicted. (nih.gov)
  • IGF-1 (2 - 7.5 ng ml(-1)) potently augmented this PDE activity. (strath.ac.uk)
  • No differences in activity or levels of cGMP-dependent protein kinase 1 or sGC were observed in Ercc1 d/- mice vs. WT. (clinsci.org)
  • The effect of cGMP (cyclic GMP) dependent protein kinase 1-β (PKG1-β) and cGMP analogues on transcriptional activity and replication of human immunodeficiency virus type 1 (HIV-1) was investigated. (biomedcentral.com)
  • Interestingly, to our knowledge, no systematic investigation of cGMP/PKG's activity on the HIV-1 LTR has been reported to date. (biomedcentral.com)
  • PKG1β was found to increase Tat dependent transcriptional activity of the HIV-1 LTR by four fold. (biomedcentral.com)
  • The I154F mutation inhibits CdA activity by binding to it more strongly than wild-type GImM binds. (wikipedia.org)
  • 42 , 43 Cyclic-AMP (cAMP) downmodulates this positive signaling wave by suppressing SYK and PI3Kδ activity. (bloodjournal.org)
  • Gurban, A. Pharmacologic activity of phosphodiesterases and their inhibitors. (eurekaselect.com)
  • Using RNA interference, we found that NCS-1 knockdown enhanced neurite extension and branching, and reduced activity-dependent Ca 2+ influx in growth cones. (biologists.org)
  • A quantitative model for the kinetics of cAMP-dependent protein kinase (type II) activity. (springer.com)
  • These included the MSIS psychological subscore and functional abilities evaluated with the MS Functional Composite index, both overall and for individual types of activity. (msrc.co.uk)
  • However, when intact platelets were incubated with NO and then lysed, enhanced activity of phosphodiesterase type 5 was detected in the cytosol. (rupress.org)
  • Thus, our data suggest that NO-induced desensitization of the cGMP response is caused by the phosphorylation and subsequent activity increase of phosphodiesterase type 5. (rupress.org)
  • Steady-state activation of cardiac β-adrenergic receptors leads to an intracellular compartmentation of cAMP resulting from localized cyclic nucleotide phosphodiesterase (PDE) activity. (ahajournals.org)
  • Independently, the fold induction of PDE activity by insulin (insulin-induced/basal) was 1.7-fold in control mice, but was reduced to 1.35-fold in IRS-1 (-/-) mice. (elsevier.com)
  • Compounds 1 ( ESI-05) , 14c ( HJC0338 ) and 20i , selected from each series, have exhibited no inhibition of EPAC1-mediated Rap1-GDP exchange activity at 25 µM, indicating that they are EPAC2-specific antagonists. (pubmedcentralcanada.ca)
  • Using immunoblotting and radioenzymatic assay we showed that total cardiac cAMP and cGMP PDE activity and specific PDE2 activity was strongly increased in PDE2 TG compared to wild type (WT) mice. (worldcat.org)
  • The cut2 mutant has reduced extracellular cutin-degrading and Ser esterase activity, when grown on cutin as the sole carbon source, compared with the wild-type strain. (plantcell.org)
  • The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process and further suggesting that daf-21 acts at a similar step. (genetics.org)
  • The baseline luciferase activity in PC-3 cells transfected with the wild-type DR5 reporter was significantly augmented in cells transfected with DR5 constructs carrying deletions or mutation in the YY1-binding site. (aacrjournals.org)
  • Treatment with drug enhanced DR5 wild-type luciferase activity, with no increase in cells transfected with the YY1-deleted or YY1-mutated constructs. (aacrjournals.org)
  • Tolerance to nitrates occurs during chronic exposure, and the current study assessed whether this was due to increased phosphodiesterase (PDE) activity in the venous circulation. (aspetjournals.org)
  • The targeting cassette disrupted a portion of exon 17, which normally encodes the third helix of the catalytic domain ( 18 ) ( Fig. 1 A ). All PDE catalytic domains studied so far have similar three-dimensional structures ( 19 ), and this N-terminal region of the catalytic core is crucial for the activity ( 20 ). (pnas.org)
  • Yet, it was demonstrated for the first time in vivo that moderate consumption of coffee can modulate the activity of platelet phosphodiesterases in humans in long and short term. (uni-kl.de)
  • Strain KD-1 possessed extracellular keratinase, and the optimum activity of the crude enzyme was pH 8.5 and 70 °C. The enzyme was identified as a thermostable serine-type protease. (vegfrsignaling.com)
  • Furthermore, other experiments are needed to shed more light on the role of NCS-1 and other mechanisms linked to signaling pathways related to inhibitory avoidance task. (labome.org)
  • These "upstream" events culminate in the activation of downstream, prosurvival, signaling pathways, including among others NF-κB, MAPK, and the AKT/mTOR complex 1 (mTORC1). (bloodjournal.org)
  • 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. (uams.edu)
  • Cyclic Nucleotide Phosphodiesterases, Type 3" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uams.edu)
  • The gut hormone glucagon like peptide-1 (GLP-1) has been shown to have important effects on maintaining the function and health of the insulin producing beta cells. (bioportfolio.com)
  • 6. IBMX, Org 9935, siguazodan and rolipram (1 - 50 microM), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. (strath.ac.uk)
  • 7. These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion. (strath.ac.uk)
  • However, islets can regulate glucagon over a glucose concentration range that is not associated with changes in insulin or somatostatin ( 7 ), and prediabetic NOD and KK mice show elevated fasting and nonfasting plasma glucagon levels without changes in plasma insulin or blood glucose ( 1 - 3 , 8 ). (diabetesjournals.org)
  • It concerns a novel conjugation chemistry that is tailored to direct a GLP-1 analog to the peripheral circulation to stimulate insulin secretion, but not to the central nervous system so that the side effects of nausea and vomiting are minimized. (upstate.edu)
  • Restoration of Glucose-Stimulated Cdc42-Pak1 Activation and Insulin Secretion by a Selective Epac Activator in Type 2 Diabetic Human Islets. (upstate.edu)
  • Type 1 diabetes (T1D) is caused by the immune system inappropriately attacking the cells in the pancreas that produce insulin, the hormone that controls blood sugar levels. (psychcentral.com)
  • Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the antilipolytic action of insulin. (elsevier.com)
  • Thus, PDE3B gene expression may be inversely correlated with a fat cell size, whereas insulin-induced PDE3B activation is mediated through IRS-1. (elsevier.com)
  • Using sub-cellular fractionation, confocal microscopy and transmission electron microscopy of isolated mouse islets and INS-1 (832/13) cells, we show that endogenous and overexpressed PDE3B is localized to insulin granules and plasma membrane. (lu.se)
  • Inhibition of sperm phosphodiesterase (PDE) has been shown to increase cAMP concentrations and stimulate motility and the acrosome reaction. (nih.gov)
  • cAMP can influence cell growth, differentiation, and movement as well as regulating specialized actions unique to specific cell types. (mcponline.org)
  • The principal target of cAMP is cAMP-dependent protein kinase (PKA) 1 . (mcponline.org)
  • cAMP-phosphodiesterase in the synaptic regions of Drosophila brains. (springer.com)
  • The likelihood that these effects are mediated by cAMP via inhibition of a Ca 2+ -calmodulin-activated phosphodiesterase is discussed and related to other data. (illinois.edu)
  • To evaluate the time course of the cAMP changes in the different compartments, brief (15 seconds) pulses of isoprenaline (100 nmol/L) were applied to adult rat ventricular myocytes (ARVMs) while monitoring cAMP changes beneath the membrane using engineered cyclic nucleotide-gated channels and within the cytosol with the fluorescence resonance energy transfer-based sensor, Epac2-camps. (ahajournals.org)
  • cAMP kinetics in the two compartments were compared to the time course of the L-type Ca 2+ channel current ( I Ca,L ) amplitude. (ahajournals.org)
  • Indeed, the presence of subcellular compartments with different cAMP concentrations, also called cAMP microdomains, are inferred from L-type Ca 2+ channel current ( I Ca,L ) measurements in response to local β-AR stimulation in cardiomyocytes 5 and by direct monitoring of cAMP using fluorescence resonance energy transfer (FRET)-based sensors 6,7 or cyclic nucleotide-gated (CNG) channels. (ahajournals.org)
  • Morphological and pathogenicity defects in the cut2 mutant are fully restored with exogenous application of synthetic cutin monomers, cAMP, 3-isobutyl-1-methylxanthine, and diacylglycerol (DAG). (plantcell.org)
  • They establish local cAMP pools by controlling the intensity, duration and compartmentalization of cyclic nucleotide-dependent signaling. (mdpi.com)
  • We also report that an M. xanthus CbpB containing two cyclic AMP (cAMP)-binding domains is involved in osmotic and temperature tolerance ( 11 ). (asm.org)
  • Campos and Zusman also observed that the formation of fruiting bodies was stimulated by the addition of cAMP to agar containing low levels of nutrients ( 1 ). (asm.org)
  • A cAMP phosphodiesterase gene ( cpdA )-disrupted Escherichia coli or Salmonella enterica serovar Typhimurium strain showed about 2- or 1.3-fold higher intracellular cAMP than the wild-type strain, respectively ( 2 , 6 ). (asm.org)
  • Two cyclic-nucleotide phosphodiesterases (DdPDE 1 and 2) have been identified previously, an extracellular dual-specificity enzyme and an intracellular cAMP-specific enzyme (encoded by the psdA and regA genes respectively). (embl.de)
  • The resulting holoenzyme isoforms differ in cell type-specificity, developmental expression, sub-cellular localization, and affinity to cAMP, thereby accounting for the pleiotropic functions of cAMP signalling. (nature.com)
  • a second effect is the inhibition of phosphodiesterases with the subsequent accumulation of cAMP and an intensification of the effects of catecholamines. (uni-kl.de)
  • Treatment of HIV-1 AD8-infected monocyte derived macrophages (MDMs) with cGMP agonists and cGMP antagonists caused respectively increased and decreased virus replication. (biomedcentral.com)
  • This includes a few exogenous, vertically transmitted and endogenous viruses of mice (type B) and some primate and sheep viruses (type D). MAMMARY TUMOR VIRUS, MOUSE is the type species. (bioportfolio.com)
  • Elevated fasting plasma glucagon levels ( 1 ) and reduced suppression of glucagon secretion after hyperglycemia ( 2 , 3 ) occurs in NOD mice and in spontaneously diabetic KK mice. (diabetesjournals.org)
  • Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular arrhythmias in mice. (nih.gov)
  • In IRS-1 (-/-) mice, PDE3B mRNA and protein levels were increased 1.24- and 1.35-fold those in C57BL/6J control mice, respectively. (elsevier.com)
  • Sarcomere shortening, Ca2+ transients and the whole L-type Ca2+ current (ICa,L) were recorded in adult ventricular myocytes from WT and PDE2 TG mice and isoprenaline (ISO) was used to examine and compare the [beta]-adrenergic ([beta]-AR) response of these parameters. (worldcat.org)
  • Effect of phosphodiesterase (1B, 2A, 9A and 10A) inhibitors on central nervous system cyclic nucleotide levels of rats and mice. (annals.org)
  • The PDE8A knockout (KO) mice were generated by replacing 38 nucleotides in the PDE8A gene with a targeting cassette containing the LacZ gene encoding a modified β-galactosidase, including the simian virus 40 large tumor nuclear localization signal, and Neo resistance. (pnas.org)
  • Biochemical data suggest the presence of at least one cGMP-specific phosphodiesterase (PDE) that is activated by cGMP. (embl.de)
  • Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. (embl.de)
  • Cyclic di-AMP is synthesized by a membrane-bound diadenylate cyclase (also called diadenylyl cyclase, CdA, and DAC) enzyme called CdaA (DacA). (wikipedia.org)
  • GImM is the phosphoglucosamine mutase enzyme that interconverts glucosamine-6-phosphate to glucosamine-1-phosphate to later form cell wall peptidoglycan and other polymers. (wikipedia.org)
  • The 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) is a highly abundant membrane-associated enzyme in the myelin sheath of the vertebrate nervous system. (jove.com)
  • The enzyme is about twice as active in vitro in 1-10 mM Mn2+ than in the same concentration of Mg2+ or Ca2+. (embl.de)
  • A partial characterization of the cyclic nucleotide phosphodiesterases of Drosophila melanogaster. (springer.com)
  • Identification and characterization of DdPDE3, a cGMP-selective phosphodiesterase from Dictyostelium. (embl.de)
  • Origin of Exopolyphosphatase Processivity: Fusion of an ASKHA Phosphotransferase and a Cyclic Nucleotide Phosphodiesterase Homolog. (purdue.edu)
  • www.who.int/gho/publications/world_health_statistics/ 2017/en/ (Accessed June 10, 2018). (eurekaselect.com)
  • Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia. (semanticscholar.org)
  • A) Schematic representations are shown of full length PKG1β (pCMV-PKG1β FLAG) and two deletion mutants, pCMV-PKG1β 1-417 FLAG and pCMV-PKG1β Δ349FLAG. (biomedcentral.com)
  • dunce mutants of Drosophila melanogaster: Mutants defective in the cyclic AMP phosphodiesterase system. (springer.com)
  • daf-11 and daf-21 mutants have similar defects in several of these responses (reviewed in R iddle and A lbert 1997 ), suggesting that the daf-11 and daf-21 gene products (DAF-11 and DAF-21) act at the same step to regulate chemosensory transduction in several types of sensory neurons. (genetics.org)
  • However, the spores of mutants, especially the pdeA and pdeB mutants, placed under osmotic stress germinated earlier than the wild-type spores. (asm.org)
  • These findings provide evidence that cGMP and PKG serve to regulate HIV-1 infection in human cells. (biomedcentral.com)
  • Our findings suggest that at least two separate structural domains in NCS-1 independently regulate Ca 2+ influx and neurite outgrowth, with the C-terminus specifically affecting branching. (biologists.org)
  • Although some studies showed the efficacy of phosphodiesterase (PDE) inhibitors as neuronal plasticity enhancers, little is known about the effectiveness of these drugs to improve plasticity in cases of mental retardation. (jneurosci.org)
  • Studies have shown that a certain concentration of RA can induce P19 cells to differentiate into neuronal cells, including neurons and glial cells, whereas 0.5% - 1% DMSO led P19 cells to differentiate into cardiac or skeletal muscle cells. (wikipedia.org)
  • Brindley, M. A., L. Hughes, A. Ruiz, P. B. McCray, Jr., A. Sanchez, D. A . Sanders, and W. Maury (2007) Ebola virus glycoprotein 1: Identification of residues important for binding and postbinding events. (purdue.edu)
  • It always involves more than one amino acid and includes all residues involved in nucleotide-binding. (uniprot.org)