Cyclic nucleotide phosphodiesterases type 1. Medical search

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)

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 ...

https://en.wikipedia.org/wiki/PDE4A

Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... "Effect of pentoxifylline on diabetic distal polyneuropathy in type 2 diabetic patients: A randomized trial". Journal of ... Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which ... the effects of non-specific phosphodiesterase inhibition". Clinics. 63 (3): 321-328. doi:10.1590/S1807-59322008000300006. PMC ...

https://en.wikipedia.org/wiki/Pentoxifylline

... 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 ...

https://en.wikipedia.org/wiki/Neuronal_calcium_sensor-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; ...

https://en.wikipedia.org/wiki/P19_cell

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). 5'-pApA is ... "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9 ...

https://en.wikipedia.org/wiki/Cyclic_di-AMP

"Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme (EC 3.1.4.17) from the phosphodiesterase class. ... Fertel R, Weiss B (July 1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" ( ... Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ...

https://en.wikipedia.org/wiki/CGMP-specific_phosphodiesterase_type_5

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 ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide

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 ...

https://en.wikipedia.org/wiki/PDE1C

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- ...

https://en.wikipedia.org/wiki/PDE9A

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 ...

https://en.wikipedia.org/wiki/PDE8B

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 ...

https://en.wikipedia.org/wiki/Phosphodiesterase_3

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 ... Cyclic Nucleotide Phosphodiesterases: Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated ... Weiss, B. and Winchurch, R.A.: Analyses of cyclic nucleotide phosphodiesterases in lymphocytes from normal and aged leukemic ...

https://en.wikipedia.org/wiki/Benjamin_Weiss_(scientist)

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 ...

https://en.wikipedia.org/wiki/Caffeine-induced_anxiety_disorder

cGAMP was found to be much more potent than other cyclic di-nucleotides (c-di-GMP and c-di-AMP). cGAMP was shown to ... "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 339 (6121): 786-91. ... 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 ...

https://en.wikipedia.org/wiki/CGAS–STING_cytosolic_DNA_sensing_pathway

"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 ...

https://en.wikipedia.org/wiki/EHNA

"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 ...

https://en.wikipedia.org/wiki/PDE6B

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. ...

https://en.wikipedia.org/wiki/Phosphodiesterase_inhibitor

"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor". British Journal of ... 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. ... Moustafa, F; Feldman, SR (16 May 2014). "A Review of Phosphodiesterase-Inhibition and the Potential Role for Phosphodiesterase ...

https://en.wikipedia.org/wiki/Phosphodiesterase-4_inhibitor

... 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 ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D08)

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 central nervous system (CNS). Oligodendrocytes were discovered by Pío del ... Oligodendrocytes (from Greek 'cells with a few branches'), or oligodendroglia, are a type of neuroglia whose main functions are ...

https://en.wikipedia.org/wiki/Oligodendrocyte

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 ...

https://en.wikipedia.org/wiki/ABCC5

Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects". The Journal of Biological Chemistry. 281 (20 ... "Binding and functional comparisons of two types of tumor necrosis factor antagonists". The Journal of Pharmacology and ... 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 ...

https://en.wikipedia.org/wiki/TNF_inhibitor

... 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 ... 116 ( Pt 1) (1): 147-159. doi:10.1093/brain/116.1.147. PMID 7680933. Roy A, Hooper DC (August 2007). "Lethal silver-haired bat ... 28 (1): 1-17. doi:10.1002/jnr.490280102. PMID 1710279. S2CID 8598890. Eylar EH, Brostoff S, Hashim G, Caccam J, Burnett P ( ...

https://en.wikipedia.org/wiki/Myelin_basic_protein

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 ...

https://en.wikipedia.org/wiki/GAF_domain

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 ...

https://en.wikipedia.org/wiki/Paraxanthine

... cAMP binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding ... cyclic monophosphate (8-Br-cAMP) Acrasin specific to chemotactic use in Dictyostelium discoideum. phosphodiesterase 4 (PDE 4) ... If a cell lacks GM1 the toxin most likely binds to other types of glycans, such as Lewis Y and Lewis X, attached to proteins ... Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in ...

https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate

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 ...

https://en.wikipedia.org/wiki/Discovery_and_development_of_phosphodiesterase_5_inhibitors

... cyclic-nucleotide 2′-phosphodiesterase EC 3.1.4.17: 3′,5′-cyclic-nucleotide phosphodiesterase EC 3.1.4.18: Now EC 3.1.16.1, ... type I site-specific deoxyribonuclease EC 3.1.21.4: type II site-specific deoxyribonuclease EC 3.1.21.5: type III site-specific ... cyclic-GMP phosphodiesterase EC 3.1.4.36: Now with EC 3.1.4.43 EC 3.1.4.37: 2′,3′-cyclic-nucleotide 3'-phosphodiesterase EC 3.1 ... phosphodiesterase * EC 3.1.4.59: cyclic-di-AMP phosphodiesterase * EC 3.1.4.60: pApA phosphodiesterase * EC 3.1.4.61: cyclic 2, ...

https://en.wikipedia.org/wiki/List_of_EC_numbers_(EC_3)

"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 ...

https://en.wikipedia.org/wiki/Phosphodiesterase

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 ...

https://en.wikipedia.org/wiki/Taste_receptor

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 selectively toxic to rapidly growing cells, therefore methotrexate is often used in ... cyclic guanosine monophosphate. This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... 381-382 Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results ...

https://en.wikipedia.org/wiki/Enzyme_inhibitor

This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic ... The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". ... cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene. ...

https://en.wikipedia.org/wiki/PDE4B

Cyclic GMP possibly opens cyclic nucleotide-gated (CNG) K+-selective channels, thereby causing hyperpolarization of the ... Kong, N., Xu, X., Zhang, Y., Wang, Y., Hao, X., Zhao, Y., Qiao, J., Xia, G. and Zhang, M. (2017) Natriuretic peptide type C ... The cGMP signal is terminated by the hydrolysis of cGMP through phosphodiesterase (PDE) activity and inactivation of GC. On ... The consequential hyperpolarization activates hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. The ...

https://en.wikipedia.org/wiki/Sperm_chemotaxis

"Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... These proteins degrade the second messenger cAMP, which is a key signal transduction molecule in multiple cell types, including ... "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene. The PDE4D gene is ...

https://en.wikipedia.org/wiki/PDE4D

Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... The regulatory N-terminus is substantially different in various phosphodiesterase types. They are flanked by the catalytic core ... Kakkar R, Raju RV, Sharma RK (July 1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)". Cell. Mol. Life ... Dousa TP (January 1999). "Cyclic-3′,5′-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney ...

https://en.wikipedia.org/wiki/PDE1

Phosphodiesterases break down cAMP, producing an inhibitory effect in neurons. KORs also couple to inward-rectifier potassium ... Tallent M, Dichter MA, Bell GI, Reisine T (December 1994). "The cloned kappa opioid receptor couples to an N-type calcium ... an in vivo fast-cyclic voltammetry study". The Journal of Pharmacology and Experimental Therapeutics. 284 (1): 151-61. PMID ... on the mouse R1.1 thymoma cell line is coupled to adenylyl cyclase through a pertussis toxin-sensitive guanine nucleotide- ...

https://en.wikipedia.org/wiki/Κ-opioid_receptor

... resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of ... There are two types of centre-surround structures in the retina - on-centres and off-centres. On-centres have a positively ... This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, ... Although each cell type differentiates from the RPCs in a sequential order, there is considerable overlap in the timing of when ...

https://en.wikipedia.org/wiki/Retina

... s are a type of phosphodiesterase inhibitors. Inhibition of the PDE isoenzyme 3 leads to an increase of ... Most studies used analogues of the nucleotide substrates or derivatives of natural product inhibitors such as xanthine (e.g. ... intracellular concentrations of the second messenger cyclic adenosine monophosphate (cAMP). cAMP mediates the phosphorylation ... A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of ...

https://en.wikipedia.org/wiki/PDE3_inhibitor

"Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte". Development. 136 (11): ... The pathway is further refined to include context-specific annotations such as species, cell/tissue type, or disease type. The ... A new mode of data visualization including time-course, single nucleotide polymorphism (SNP), and splicing, has been ... and are regulated by the phosphodiesterase (PDE). This pathway can be triggered via two mechanisms: physiological stimulus ( ...

https://en.wikipedia.org/wiki/Biochemical_cascade

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 also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase. Caffeine is a bitter, white ... As a competitive nonselective phosphodiesterase inhibitor, caffeine raises intracellular cyclic AMP, activates protein kinase A ...

https://en.wikipedia.org/wiki/Caffeine

The number is the position of the nucleotide from the 5' end; the first letter represents the wild-type nucleotide, and the ... Whole genome sequencing results revealed that when Cyclic-di-AMP phosphodiesterase (GdpP) was disrupted in this bacterium, it ... The nomenclature specifies the type of mutation and base or amino acid changes. Nucleotide substitution (e.g., 76A>T) - ... These type of mutation have led to new types of fruits, such as the "Delicious" apple and the "Washington" navel orange. Human ...

https://en.wikipedia.org/wiki/Mutation

Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound ... Rather, it is the ratios of responses of the three types of cone cells that can estimate wavelength, and therefore enable color ... Each transducin then activates the enzyme cGMP-specific phosphodiesterase (PDE). PDE then catalyzes the hydrolysis of cGMP to 5 ... resulting in the closure of cyclic nucleotide-gated Na+ ion channels located in the photoreceptor outer segment membrane. As a ...

https://en.wikipedia.org/wiki/Photoreceptor_cell

... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... April 2007). "A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis ... characteristic of the highly conserved guanine nucleotide exchange factors. Mutations in this gene have been associated with X- ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ...

https://en.wikipedia.org/wiki/Retinitis_pigmentosa_GTPase_regulator

Kroll, S.; Phillips, W. J.; Cerione, R. A. (1989). "The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of ... Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". ... It is a type of heterotrimeric G-protein with different α subunits in rod and cone photoreceptors. Light leads to ... Transducin activates phosphodiesterase, which results in the breakdown of cyclic guanosine monophosphate (cGMP). The intensity ...

https://en.wikipedia.org/wiki/Transducin

Bifulco M, Laezza C, Stingo S, Wolff J (February 2002). "2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, ... Mutations to the TUBA1A gene manifest clinically as Type 3 Lissencephaly. In general, lissencephaly is characterized by agyria ... with respect to wild-type counterparts), showing that the S140G mutation has value as a model for detailing disease associated ... while attribution to a specific type is obtained by microarray. Treatment is symptomatic; anti-convulsive drugs for seizure ...

https://en.wikipedia.org/wiki/Tubulin_alpha-1A_chain

... which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation causes extremely high ... Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the ... Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on ... to cyclic guanosine monophosphate (cGMP) and pyrophosphate: GTP = 3′,5′-cyclic GMP + diphosphate It is often part of the G ...

https://en.wikipedia.org/wiki/Guanylate_cyclase

Cyclic Nucleotide Phosphodiesterases, Type 1B*Cyclic Nucleotide Phosphodiesterases, Type 1B. *Phosphodiesterase 1B, Calmodulin- ... Cyclic Nucleotide Phosphodiesterases, Type 1C*Cyclic Nucleotide Phosphodiesterases, Type 1C. *Phosphodiesterase 1C, Calmodulin- ... Cyclic Nucleotide Phosphodiesterases, Type 1A*Cyclic Nucleotide Phosphodiesterases, Type 1A. *Phosphodiesterase 1A, Calmodulin- ... 3,5-Cyclic-AMP Phosphodiesterases [D08.811.277.352.640.150]. *Cyclic Nucleotide Phosphodiesterases, Type 1 [D08.811.277.352. ...

https://profiles.uchicago.edu/profiles/display/32242

Cyclic Nucleotide Phosphodiesterases, Type 1 Actions. * Search in PubMed * Search in MeSH ... Cyclic nucleotide phosphodiesterases and human arterial smooth muscle cell proliferation. Rybalkin SD, Bornfeldt KE. Rybalkin ... Phosphodiesterase 1 upregulation in pulmonary arterial hypertension: target for reverse-remodeling therapy Ralph Theo Schermuly ... Microvascular Sex- and Age- Dependent Phosphodiesterase Expression. Wang J, Kazmi MM, Huxley VH. Wang J, et al. Front Aging. ...

https://pubmed.ncbi.nlm.nih.gov/17438150/

https://www.ncbi.nlm.nih.gov/pubmed/17438150

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in ... Type III cyclic nucleotide phosphodiesterases and insulin action.. Manganiello VC; Degerman E; Taira M; Kono T; Belfrage P. ... 2. Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1).. Kakkar R; Raju RV; Sharma RK. Cell Mol Life Sci; 1999 Jul ... 7. Inhibitors of cyclic nucleotide phosphodiesterase 3 and 5 as therapeutic agents in heart failure.. Stehlik J; Movsesian MA. ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=8646851&mod=related&page=1&outid=&proj=

Type 1A Cyclic Nucleotide Phosphodiesterases, Type 1B Cyclic Nucleotide Phosphodiesterases, Type 1C Cyclic Nucleotide ... Cyclic Nucleotide Phosphodiesterases, Type 2 [D08.811.277.352.640.150.200] * Cyclic Nucleotide Phosphodiesterases, Type 3 [ ... Cyclic Nucleotide Phosphodiesterases, Type 4 [D08.811.277.352.640.150.400] * Cyclic Nucleotide Phosphodiesterases, Type 5 [ ... Cyclic Nucleotide Phosphodiesterases, Type 6 [D08.811.277.352.640.150.600] * Cyclic Nucleotide Phosphodiesterases, Type 7 [ ...

https://meshb.nlm.nih.gov/record/ui?ui=D054677

CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1986-2007, for CALMODULIN PHOSPHODIESTERASE use 3,5-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ... A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type ... class have additional specificity for CYCLIC-GMP. HN - 2008(2000) MH - Cyclic Nucleotide Phosphodiesterases, Type 3 UI - ...

https://decs.bvs.br/I/dcsnew2008.txt

https://meshb-prev.nlm.nih.gov/record/ui?ui=D054677

Type 1A. Cyclic Nucleotide Phosphodiesterases, Type 1B. Cyclic Nucleotide Phosphodiesterases, Type 1C. Cyclic Nucleotide ... Cyclic Nucleotide Phosphodiesterase PDE1 Family Cyclic Nucleotide Phosphodiesterases, Type I PDE1 Phosphodiesterases ... Cyclic Nucleotide Phosphodiesterases, Type 1B - Narrower Concept UI. M0506859. Preferred term. Cyclic Nucleotide ... Cyclic Nucleotide Phosphodiesterases, Type 1C - Narrower Concept UI. M0506860. Preferred term. Cyclic Nucleotide ...

https://decs.bvsalud.org/en/ths/resource/?id=52676

... particularly cyclic nucleotide phosphodiesterases (PDEs). MAIN METHODS: Type 1 diabetes (T1D) was induced in rats by ... Cardiac Phosphodiesterases Are Differentially Increased in Diabetic Cardiomyopathy. Hanna, Rita; Nour-Eldine, Wared; Saliba, ... Results The most prevalent blood type was A (42%), followed by O (37.48%), B (13.86%), and the AB group (6.84%). RhD+ groups ... Conclusion This study on blood type prevalence and blood donor demographics may pave the way for the development of a more ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=au:Saliba,+Youakim

Among the 11 isoforms of phosphodiesterases (PDEs), the most important are the PDE3 and PDE5 isoforms, which degrade cyclic ... leading to the conversion of guanosine triphosphate nucleotide into cyclic guanosine monophosphate (cGMP). The increase in ... or nitric oxide synthase type 3) is the most extensively studied enzyme in persistent pulmonary hypertension of the newborn ( ... 9, 10] cGMP is down-regulated by phosphodiesterase 5 activity. Phosphodiesterase 5, which is abundantly expressed in lung ...

https://emedicine.medscape.com/article/898437-overview

Cyclic-GMP Phosphodiesterase N0000167617 3,5-Cyclic-Nucleotide Phosphodiesterase N0000166404 3,3-Diaminobenzidine ... Myosin Type I N0000169441 Myosin Type II N0000169436 Myosin Type III N0000169437 Myosin Type IV N0000169440 Myosin Type V ... Cyclic N-Oxides N0000170595 Cyclic Nucleotide-Regulated Protein Kinases N0000167036 Cyclic P-Oxides N0000167037 Cyclic S-Oxides ... Type I N0000168667 Collagen Type II N0000168664 Collagen Type III N0000168677 Collagen Type IV N0000168674 Collagen Type IX ...

https://evs.nci.nih.gov/ftp1/FDA/ndfrt/Archive/StructuralClass%202007-10-09.txt

Cyclic Nucleotide Phosphodiesterases, Type 5. A. F. Teich, Sakurai, M., Patel, M., Holman, C., Saeed, F., Fiorito, J., and ... Cyclic Nucleotide Phosphodiesterases, Type 6. M. W. Granger, Franko, B., Taylor, M. W., Messier, C., St George-Hyslop, P., and ... Cyclic Nucleotide-Gated Cation Channels. M. Wang, Gamo, N. J., Yang, Y., Jin, L. E., Wang, X. - J., Laubach, M., Mazer, J. A., ... Cyclic AMP. M. Wang, Gamo, N. J., Yang, Y., Jin, L. E., Wang, X. - J., Laubach, M., Mazer, J. A., Lee, D., and Arnsten, A. F. T ...

https://www.j-alz.com/biblio?page=36&f%5Bkeyword%5D=C&s=keyword&o=asc

Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile ... with upregulation of both monomeric and dimerized forms of protein kinase G and of the cGMP hydrolyzing phosphodiesterases 2 ... protein phosphatase 1 and protein phosphatase 2 A abundance following phosphodiesterase 5 inhibition. ... Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure *Michael E. J. Preedy ...

https://www.nature.com/articles/s41598-019-42592-1?utm_source=sciencenet&utm_medium=display&utm_content=leaderboard&utm_campaign=JRCN_2_RL_sciencenet_article_english_s41598-019-42592-1&error=cookies_not_supported&code=ce1491da-7d82-4df3-9d0d-1c31b1617029

Mouse model for Usher syndrome type 1D (NIDCD). Transgenic mouse model of a targeted disruption of a cyclic nucleotide ... phosphodiesterase gene provides new insights into the regulation of insulin homeostasis (NHLBI) ... that inhibiting the type I receptor or stimulating the type 2 receptor might be therapeutically useful in such conditions as ... Diagnostic approaches based on immunological detection of the Pseudomonas aeruginosa type III secretory apparatus and its ...

https://nihsearch.cit.nih.gov/catalyst/2002/02.05.01/page3.html

... cyclic- nucleotide 3′-Phosphodiesterase. Wilson, S. J., Schoggins, J. W., Zang, T., Kutluay, S. B., Jouvenet, N., Alim, M. A., ... Regulation of histone deposition on the herpes simplex virus type 1 genome during lytic infection. Kutluay, S. B. & Triezenberg ... Nucleotide resolution mapping of influenza A virus nucleoprotein-RNA interactions reveals RNA features required for replication ... Transcriptional coactivators are not required for herpes simplex virus type 1 immediate-early gene expression in vitro. Kutluay ...

https://profiles.wustl.edu/en/persons/sebla-kutluay/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle

3. Phosphodiesterase, an enzyme, is then activated. 4. Cyclic nucleotide, cNMP, is used, lowering the concentration 5. Channels ... Glutamate binds to a variant of G protein coupled glutamate receptors.[49][50] L-glutamate may bond to a type of GPCR known as ... The amino acid glutamic acid is responsible for savoriness,[68][69] but some nucleotides (inosinic acid[44][70] and guanylic ... Each type of receptor has a different manner of sensory transduction: that is, of detecting the presence of a certain compound ...

https://en.wikipedia.org/wiki/Basic_taste

Type 4 Cyclic Nucleotide Phosphodiesterase 100% * Antidepressive Agents 61% * Fluoxetine 39% * Seizures 35% ... Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain. Monteggia, L. ... Differential expression and regulation of the cAMP-selective phosphodiesterase type 4A splice variants in rat brain by chronic ... Chen, A. C. H., Eisch, A. J., Sakai, N., Takahashi, M., Nestler, E. J. & Duman, R. S., 2001, In: Synapse. 39, 1, p. 42-50 9 p. ...

https://utsouthwestern.elsevierpure.com/en/persons/amelia-j-eisch/publications/?ordering=publicationYearThenTitle&descending=false

... or by inhibition of cyclic nucleotide phosphodies-terase. Voltage-sensitive Ca2+ channel activity increases slowly over a ... Various types of synapse defects were detected; including defects in voltage-sensitive 45Ca2+ channels, vesicles, and an ... or exposure to various cyclic nucleotide phosphodiesterase inhibitors, markedly increases the number of synapses formed. The ... Receptor-mediated increases in intracellular cyclic AMP or cyclic GMP levels had no immediate effect on K+-dependent 45Ca2+ ...

https://collections.nlm.nih.gov/ocr/nlm:nlmuid-101584910X253-doc

Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases. Reinhardt, R. R., ... Distinct heparan sulfate compositions in wild-type and pipe-mutant eggshell matrix. Park, Y., Zhang, Z., Linhardt, R. J. & ... Distinct growth phases in early life associated with the risk of type 1 diabetes: The teddy study. TEDDY study group, Mar 1 ... Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness ...

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Cyclic Nucleotide Phosphodiesterases, Type 3*; Mice; Nucleotides, Cyclic*; Phosphorylation; Signal Transduction ... Title: Nitration of protein kinase G-Iα modulates cyclic nucleotide crosstalk via phosphodiesterase 3A: Implications for acute ... Abstract: Phosphodiesterase 3A (PDE3A) selectively cleaves the phosphodiester bond of cAMP and is inhibited by cGMP, making it ... MeSH Terms: Acute Lung Injury*; Animals; Cyclic GMP-Dependent Protein Kinases*; ...

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Phosphodiesterases catalyze the hydrolysis of the phosphodiester bond in dye-labeled cyclic monophosphates. Beads selectively ... This increases the size of the nucleotide relative to unreacted cyclic monophosphate. In the polarization assay, dye molecules ... Products Types. ◆ Recombinant Protein. Pde7b-4752M. Recombinant Mouse Pde7b Protein, Myc/DDK-tagged. +Inquiry. ... Phosphodiesterases (PDEs) play an important role in the dynamic regulation of cAMP and cGMP signaling. PDE7B is highly ...

https://www.creativebiomart.net/pde7b-assay-kit-465733.htm

I am studying 23 cyclic nucleotide 3 phosphodiesterase ( cnp) is a oligodedrocyte, that means that it mylinates but how? Also ...

https://www.khanacademy.org/science/health-and-medicine/nervous-system-and-sensory-infor/neural-cells-and-neurotransmitters/v/oligodendrocytes

Type 5 Cyclic Nucleotide Phosphodiesterases 100% * Enterotoxigenic Escherichia coli 91% * Escherichia coli Infections 87% ... Phosphodiesterase 5 (PDE5) restricts intracellular cGMP accumulation during enterotoxigenic Escherichia coli infection. Foulke- ... Abel, J., Yu, H., Sunuwar, L., Lin, R., Fleckenstein, J. M., Kaper, J. B. & Donowitz, M., Nov 9 2020, In: Gut Microbes. 12, 1, ... 1, p. 219-232 14 p.. Research output: Contribution to journal › Article › peer-review ...

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AB - A calcium-dependent cyclic nucleotide phosphodiesterase from rat cerebrum was, in the absence of activator protein, ... cyclic AMP-binding proteins of bovine liver are the type I and type II regulatory subunits of cyclic AMP-dependent protein ... Force of cardiac contraction and cardiac cyclic nucleotide levels (cyclic GMP and cyclic AMP) were monitored in hearts ... micron cyclic AMP or 0.6 micron cyclic GMP was the enzyme substrate. The stimulation of adipocyte cyclic AMP phosphodiesterase ...

https://data.lhncbc.nlm.nih.gov/public/ii/information/MBR/Download/MetaMapped_Medline/2019/MEDLINE/pubmed19n0008.txt

Cyclic Nucleotide Phosphodiesterases: Therapeutic Targets Above and Below the Diaphragm. Vincent Manganiello, MD, PhD, Chief, ... An abnormal type of hemoglobin inside the red blood cells distorts their shape and interferes with blood flow.. The enzyme LDH ... Do you have Diabetes Type 1 or Type 2 and kidney disease? If so, call (866) 444-2214, TTY (866) 411-1010 to participate in ... Noon-1 p.m. Lipsett Amphitheater. Grand Rounds: Zoonoses: Where the Wild Things Are. Arnold N. Weinberg, MD, Professor of ...

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Type 3 Cyclic Nucleotide Phosphodiesterases 95% * Phosphodiesterase Inhibitors 76% * Alprostadil 74% * Microcirculation 66% ... A New Type of Micropump for Medical Application. Guo, S., Chen, X. & Fukuda, T., 1998 Aug 11, In: Proc. International ... Amrinone, a selective phosphodiesterase III inhibitor, improves microcirculation and flap survival: A comparative study with ... Amrinone, a selective phosphodiesterase III inhibitor, improves microcirculation and flap survival: a comparative study with ...

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2,3-Cyclic-Nucleotide Phosphodiesterases QU 136 Connect with NLM. *. *. *. National Library of Medicine 8600 Rockville Pike ...

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Insulin-Induced Formation of Macromolecular Complexes Involved in Activation of Cyclic Nucleotide Phosphodiesterase 3 B (PDE3B ... Age of Onset of Scoliosis in Osteogenesis Imperfecta May be Associated with Sillence Type but Not Body Mass Index ... C-1 Beck, Barbara E (NCI) B. Beck, R. Mandler, M. Zhang, K. Garmestani, M. W. Brechbiel, G. Höfle, A. Dömling, T. A. Waldmann ... ENDO-1 Gautam, Dinesh C. (NIDDK) D. Gautam, S.-J. Han, Y. Cui, J.-H. Li, C. Deng, F.F. Hamdan and J. Wess ...

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Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. (biomedcentral.com)

21(1): 171, 2023 08 11. (bvsalud.org)

A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. (uchicago.edu)
The calcium/calmodulin-dependent phosphodiesterase 1 (PDE1) may play a major role in vascular smooth muscle cell proliferation. (nih.gov)
As in aged wild-type mice, the HFS-LTP in the young adult CaMKIIΔSNO mice required L-type voltage-gated calcium ion channels. (bvsalud.org)
Vinpocetine inhibits an enzyme called PDE1 (phosphodiesterase type 1) while reducing calcium levels in brain cells. (nootropicsexpert.com)

PMID- 214392 TI - Regulation of lipogenesis by adenosine 3', 5'-cyclic monophosphate in chicken liver in vitro. (nih.gov)
PMID- 214393 TI - Regulation of growth & metabolism of ovariectomised rat uterus by adenosine 3', 5'-cyclic monophosphate. (nih.gov)
Cyclic-adenosine monophosphate (cAMP) and cyclic-guanosine monophosphate (cGMP) are the best known mechanisms related to platelet inhibitory activity. (springeropen.com)

Phosphodiesterase 3A (PDE3A) selectively cleaves the phosphodiester bond of cAMP and is inhibited by cGMP, making it an important regulator of cAMP-cGMP signaling crosstalk in the pulmonary vasculature. (nih.gov)

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. (uchicago.edu)
Aunque las enzimas de tipo 1 se clasifican como 3',5'-AMP cíclico fosfodiesterasas (EC 3.1.4.17), algunos miembros de esta clase tienen especificidad adicional por el GMP CÍCLICO. (bvsalud.org)
It also represents a related phosphodiesterase (PDEase) domain that is found in eukaryotic 3',5'-cGMP phosphodiesterase ( EC 3.1.4.17 ), which is located in photoreceptor outer segments and it is light activated, playing a pivotal role in signal transduction. (embl.de)

derivatives adenosine thiamine diphosphate (AThDP) [1] and adenosine thiamine triphosphate (AThTP) [1, 2]. (narturalproduct.com)
Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. (bvsalud.org)

11. IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells. (nih.gov)
Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. (lookformedical.com)
These cyclic nucleotides in turn activate a series of kinases that phosphorylate the transcription factors cAMP response element binding protein ( CREB ) and serum response factor ( SRF ), leading to the expression of plasticity-related genes. (nootropicsexpert.com)

Nitration of protein kinase G-Iα modulates cyclic nucleotide crosstalk via phosphodiesterase 3A: Implications for acute lung injury. (nih.gov)
Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC-AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA. (nih.gov)
Vasodilator-stimulated phosphoprotein (VASP) and inositol 1, 4, 5-triphosphate receptor type I (IP 3 RI) are major substrates of protein kinase A and protein kinase G and VASP contributes to αIIb/β 3 affinity and IP 3 RI affects [Ca 2+ ] i mobilization. (springeropen.com)

The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. (bvsalud.org)

A chemogenetic method was then used to modulate the inhibition and activation of excitatory neurons in the prelimbic cortex of wild-type and 5XFAD mice and to measure the memory capacity of mice. (bvsalud.org)
Our results further demonstrate that the chemogenetic inhibition of prelimbic cortex excitatory neurons resulted in reduced working memory capacity in wild-type mice, while the chemogenetic activation of prelimbic cortex excitatory neurons improved the working memory capacity of 5XFAD mice. (bvsalud.org)
1. STAT6 mediates interleukin-4 growth inhibition in human breast cancer cells. (nih.gov)
The type-specific antibodies were assayed by IHA inhibition test. (nih.gov)

An optimized adult brain gets about 1/7th of your heart's output of blood every minute. (nootropicsexpert.com)

Based on detailed studies of the reversible adenylyltion of E. coli glutamine synthetase (GS), Dr. Chock, in collaboration with Dr. E. R. Stadtman, formulated a cyclic cascade model, to reveal the basic principles that underlie this regulatory mechanism and its regulatory advantages in cellular regulation and signal transduction, which include an enormous potential for signal and rate amplification, regulatory sensitivity, and flexibility. (nih.gov)
The GTPase activating protein, RGS9-1, is vital for the deactivation and regulation of the phototransduction cascade (C. K. Chen et al. (ox.ac.uk)

These investigations led to the development of several TNF and IL-1 inhibitors, two of which are currently licensed Remicade (chimeric anti-TNF antibody) and Enbrel (TNF-receptor fusion protein). (biomedcentral.com)

It is now well accepted that the spontaneous production of proinflammatory cytokines (in particular, tumour necrosis factor [TNF] and IL-1) produced locally in the inflamed synovial joint contribute directly/indirectly to the pathogenesis of rheumatoid arthritis (RA) [ 1 ]. (biomedcentral.com)

Kovacikova G, Lin W, Skorupski K: Vibrio cholerae AphA uses a novel mechanism for virulence gene activation that involves interaction with the LysR-type regulator AphB at the tcpPH promoter. (narturalproduct.com)

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. (uchicago.edu)

Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP . (bvsalud.org)

Its overexpression in agouti mice results in uniform yellow coat color, OBESITY, and metabolic defects similar to type II diabetes in humans. (nih.gov)

Long-term infusion of the PDE1 inhibitor 8-methoxymethyl 3-isobutyl-1-methylxanthine in hypoxic mice and monocrotaline-injected rats with fully established pulmonary hypertension reversed the pulmonary artery pressure elevation, structural remodeling of the lung vasculature (nonmuscularized versus partially muscularized versus fully muscularized small pulmonary arteries), and right heart hypertrophy. (nih.gov)
In addition, similar to aged wild-type mice, in which CaMKII was hyponitrosylated, but unlike mice with impairments of other CaMKII autonomy mechanisms, CaMKIIΔSNO mice showed reduced long-term potentiation (LTP) when induced by theta-burst stimulation but not high-frequency stimulation (HFS). (bvsalud.org)

In the absence of other cell types in vitro , OL differentiation reproduces the in vivo development with a correct timing, suggesting the existence of an intrinsic regulatory mechanism that presently is unknown. (jneurosci.org)

Artocarpesin increased the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and inositol 1, 4, 5-triphosphate receptor I (IP 3 RI). (springeropen.com)

9. PU.1 is required for transcriptional activation of the Stat6 response element in the Igepsilon promoter. (nih.gov)

The peroxynitrite scavenger manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin prevented this increase in PDE3 activity in LPS-exposed lungs. (nih.gov)
AB - Antibody activity to Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) was measured by the indirect hemagglutination (IHA) test in sera from 124 women with squamous-cell carcinoma of the uterine cervix, 46 women with non-cervical cancer and 116 matched normal women. (nih.gov)
The predominance of type PIII metalloproteinases agrees with the well-known hemorrhagic activity of this venom, whereas the lower content of serine proteases and C-type lectins could contribute to less marked coagulopathy following envenoming by this species. (biomedcentral.com)

To address the activation mechanism and the regulatory advantages of having four Ca(II) binding sites on the calmodulin (CM), Dr. Chock and his colleagues, particularly Dr. Charles Huang, performed detailed kinetic analysis for Ca(II)CM mediated activation of cyclic nucleotide phosphodiesterase. (nih.gov)

Mol Microbiol 2000,35(1):189-203.PubMedCrossRef 14. (narturalproduct.com)

2. Multiple signaling pathways mediate interleukin-4-induced 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene expression in human breast cancer cells. (nih.gov)
Studies of the global composition of snake venoms have advanced dramatically in recent years with the introduction of transcriptomic and proteomic approaches for analyzing venom gland gene expression and venom composition [ 1 - 3 ]. (biomedcentral.com)

RESULTS: Working memory capacity was significantly diminished in 5XFAD mice compared to littermate wild-type mice. (bvsalud.org)

Two types of (missing Dst-A1 and -A2) and (missing all neuronal isoforms), possess peripheral myelination abnormalities which were due to intrinsic differentiation problems in Schwann cells [23]. (bio2009.org)

This graph shows the total number of publications written about "Cyclic Nucleotide Phosphodiesterases, Type 1" by people in this website by year, and whether "Cyclic Nucleotide Phosphodiesterases, Type 1" was a major or minor topic of these publications. (uchicago.edu)
There are three major types of cone cells (red, blue, and green) whose photopigments have different spectral sensitivity curves. (lookformedical.com)

ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells. (nih.gov)
Paradoxically, however, we find that the cone response in an observer lacking RGS9-1 is faster at lower light levels than it is in a normal observer. (ox.ac.uk)
E. N. Pugh, S. Nikonov, & T. D. Lamb, 1999), which predict that the excess of PDE6* resulting from the loss of RGS9-1 will shorten the visual integration time and speed up the visual response at inappropriately low light levels. (ox.ac.uk)
The levels of SSEA3 and TRA-1-81 antigens in NT2-RA were dropped but they increased in NT2- RA-VH to a level similar to the NT2 cells. (bvsalud.org)

PMID- 214407 TI - Antibodies to Herpes simplex virus types 1 and 2 in patients with squamous-cell carcinoma of uterine cervix in India. (nih.gov)

Histological studies of synovium in RA have indicated that this tissue is very cellular, and that several different cell types including macrophages and T cells are in close proximity [ 6 ]. (biomedcentral.com)

12. Induction of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene transcription in human breast cancer cell lines and in normal mammary epithelial cells by interleukin-4 and interleukin-13. (nih.gov)
In contrast, seropositive donor cultures seeded at the higher cell concentrations developed foci of proliferating EBNA-positive cells within the first 1--2 weeks but thereafter regressed completely and subcultures made after 4 weeks never gave rise to cell lines. (nih.gov)
Cell 1991,64(1):29-37.PubMedCrossRef 7. (narturalproduct.com)
Its biological function(s) remain unclear but, in E. coli, it was shown to accumulate transiently as a response to amino acid starvation, suggesting that it may be a signal required for rapid adaptation of the bacteria to this kind of nutritional Torin 1 cell line downshift [5]. (narturalproduct.com)
Furthermore, this signal was abrogated if physical contact between the two cell types was blocked. (biomedcentral.com)

Organisms1

Chemicals and Drugs48

Analytical, Diagnostic and Therapeutic Techniques and Equipment1

Phenomena and Processes12

Information Science3

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

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

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

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

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

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

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

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

Cyclic Nucleotide Phosphodiesterases, Type 1

3',5'-Cyclic-AMP Phosphodiesterases

Cyclic Nucleotide Phosphodiesterases, Type 4

Cyclic Nucleotide Phosphodiesterases, Type 3

Cyclic Nucleotide Phosphodiesterases, Type 2

Phosphoric Diester Hydrolases

2',3'-Cyclic-Nucleotide Phosphodiesterases

Nucleotides, Cyclic

Phosphodiesterase Inhibitors

3',5'-Cyclic-GMP Phosphodiesterases

Cyclic Nucleotide Phosphodiesterases, Type 5

Cyclic GMP

Cyclic Nucleotide Phosphodiesterases, Type 7

Cyclic AMP

Rolipram

1-Methyl-3-isobutylxanthine

Purinones

Isoenzymes

Molecular Sequence Data

Calmodulin

Amino Acid Sequence

Kinetics

Cyclic Nucleotide Phosphodiesterases, Type 6

Nucleotides

Phosphodiesterase 3 Inhibitors

Phosphodiesterase 4 Inhibitors

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone

Dibutyryl Cyclic GMP

Theophylline

Phosphodiesterase I

Cyclic Nucleotide-Gated Cation Channels

Phosphorus-Oxygen Lyases

Milrinone

Bucladesine

Pyrrolidinones

Adenine Nucleotides

Cyclic AMP-Dependent Protein Kinases

Cyclic GMP-Dependent Protein Kinases

Adenylate Cyclase

Second Messenger Systems

Papaverine

Cyclic IMP

Base Sequence

Colforsin

Guanylate Cyclase

Cloning, Molecular

Polymorphism, Single Nucleotide

Phosphodiesterase 5 Inhibitors

8-Bromo Cyclic Adenosine Monophosphate

Calcium

Guanine Nucleotides

Cattle

Hydrolysis

Isoproterenol

Xanthines

Binding Sites

Catalytic Domain

Signal Transduction

Vinca Alkaloids

Cyclic P-Oxides

Enzyme Activation

Substrate Specificity

Sequence Homology, Amino Acid

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

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

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

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

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

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

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

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

PDE4A

Pentoxifylline

Neuronal calcium sensor-1

P19 cell

Cyclic di-AMP

CGMP-specific phosphodiesterase type 5

Cyclic nucleotide

PDE1C

PDE9A