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Cyclic Nucleotide Phosphodiesterases, Type 13',5'-Cyclic-AMP PhosphodiesterasesCyclic Nucleotide Phosphodiesterases, Type 4Cyclic Nucleotide Phosphodiesterases, Type 3Cyclic Nucleotide Phosphodiesterases, Type 2Phosphoric Diester Hydrolases2',3'-Cyclic-Nucleotide PhosphodiesterasesNucleotides, CyclicPhosphodiesterase Inhibitors3',5'-Cyclic-GMP PhosphodiesterasesCyclic Nucleotide Phosphodiesterases, Type 5Cyclic GMPCyclic Nucleotide Phosphodiesterases, Type 7Cyclic AMPRolipram1-Methyl-3-isobutylxanthinePurinonesIsoenzymesMolecular Sequence DataCalmodulinAmino Acid SequenceKineticsCyclic Nucleotide Phosphodiesterases, Type 6NucleotidesPhosphodiesterase 3 InhibitorsPhosphodiesterase 4 Inhibitors4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinoneDibutyryl Cyclic GMPTheophyllinePhosphodiesterase ICyclic Nucleotide-Gated Cation ChannelsPhosphorus-Oxygen LyasesMilrinoneBucladesinePyrrolidinonesAdenine NucleotidesCyclic AMP-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesAdenylate CyclaseSecond Messenger SystemsPapaverineCyclic IMPBase SequenceColforsinGuanylate CyclaseCloning, MolecularPolymorphism, Single NucleotidePhosphodiesterase 5 Inhibitors8-Bromo Cyclic Adenosine MonophosphateCalciumGuanine NucleotidesCattleHydrolysisIsoproterenolXanthinesBinding SitesCatalytic DomainSignal TransductionVinca AlkaloidsCyclic P-OxidesEnzyme ActivationSubstrate SpecificitySequence Homology, Amino Acid
Cyclic Nucleotide Phosphodiesterases, Type 1
A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.
3',5'-Cyclic-AMP Phosphodiesterases
Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.
Cyclic Nucleotide Phosphodiesterases, Type 4
A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.
Cyclic Nucleotide Phosphodiesterases, Type 3
A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.
Cyclic Nucleotide Phosphodiesterases, Type 2
A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), members of this class have additional specificity for CYCLIC GMP.
Phosphoric Diester Hydrolases
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
2',3'-Cyclic-Nucleotide Phosphodiesterases
Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.
Nucleotides, Cyclic
Phosphodiesterase Inhibitors
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
3',5'-Cyclic-GMP Phosphodiesterases
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
Cyclic Nucleotide Phosphodiesterases, Type 5
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.
Cyclic GMP
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
Cyclic Nucleotide Phosphodiesterases, Type 7
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.
Cyclic AMP
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Rolipram
A phosphodiesterase 4 inhibitor with antidepressant properties.
1-Methyl-3-isobutylxanthine
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
Purinones
Isoenzymes
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Calmodulin
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
Amino Acid Sequence
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Kinetics
The rate dynamics in chemical or physical systems.
Cyclic Nucleotide Phosphodiesterases, Type 6
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.
Nucleotides
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Phosphodiesterase 3 Inhibitors
Compounds that specifically inhibit PHOSPHODIESTERASE 3.
Phosphodiesterase 4 Inhibitors
Compounds that specifically inhibit PHOSPHODIESTERASE 4.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
Inhibitor of phosphodiesterases.
Dibutyryl Cyclic GMP
N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.
Theophylline
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
Phosphodiesterase I
A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.
Cyclic Nucleotide-Gated Cation Channels
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
Phosphorus-Oxygen Lyases
Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.
Milrinone
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.
Bucladesine
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
Pyrrolidinones
A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)
Adenine Nucleotides
Cyclic AMP-Dependent Protein Kinases
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Cyclic GMP-Dependent Protein Kinases
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Adenylate Cyclase
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
Second Messenger Systems
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
Papaverine
An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
Cyclic IMP
Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.
Base Sequence
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Colforsin
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
Guanylate Cyclase
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.
Cloning, Molecular
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Polymorphism, Single Nucleotide
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Phosphodiesterase 5 Inhibitors
Compounds that specifically inhibit PHOSPHODIESTERASE 5.
8-Bromo Cyclic Adenosine Monophosphate
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
Calcium
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Guanine Nucleotides
Cattle
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Hydrolysis
The process of cleaving a chemical compound by the addition of a molecule of water.
Isoproterenol
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
Xanthines
Purine bases found in body tissues and fluids and in some plants.
Binding Sites
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Catalytic Domain
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Vinca Alkaloids
A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.
Cyclic P-Oxides
Enzyme Activation
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Substrate Specificity
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Sequence Homology, Amino Acid
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

Potency and mechanism of action of E4021, a type 5 phosphodiesterase isozyme-selective inhibitor, on the photoreceptor phosphodiesterase depend on the state of activation of the enzyme. (1/318)

The ability of inhibitors selective for the type 5 phosphodiesterase isozyme (PDE5) to act on the photoreceptor PDE isozyme (PDE6, the central effector enzyme for visual transduction) is poorly understood. Because PDE5 inhibitors are currently used as therapeutic agents, it is important to assess the potency and mechanism of action of this class of PDE inhibitor on PDE6. We show that E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-ca rboxylate sesquihydrate) inhibits activated PDE6 (KI = 1.7 nM) as potently as PDE5. This makes E4021 the most potent inhibitor of PDE6 discovered to date. The effectiveness of E4021 to inhibit nonactivated PDE6 (with bound inhibitory gamma subunits) is reduced 40-fold compared with the activated enzyme. Furthermore, at intermediate E4021 concentrations and high cGMP concentrations, nonactivated PDE undergoes activation of cGMP hydrolysis rather than inhibition. We demonstrate direct competition of E4021 and the gamma subunits for binding to the catalytic site. Measurements of cGMP binding to noncatalytic regulatory sites on the catalytic subunits of PDE6 rule out an allosteric effect of E4021 by direct binding to these noncatalytic sites. We conclude that E4021 is a competitive inhibitor of cGMP hydrolysis and that the gamma subunit also competes with both E4021 and substrate for catalytic site binding. An understanding of the effects of PDE5-targeted drugs on retinal PDE6 requires a knowledge of the complex interactions among substrate, drug, and inhibitory gamma subunit at the catalytic site of both nonactivated and activated forms of PDE6.  (+info)

cAMP-dependent induction of PDE5 expression in murine neuroblastoma cell differentiation. (2/318)

The present study demonstrates, in both hybrid NG108-15 and mouse neuroblastoma N18TG2 cells, the presence and regulation of PDE5 mRNA during cell differentiation. PDE5 cDNA probes in Northern blot analysis recognize a approximately 9 kb transcript in bovine lung as well as in mouse neuroblastoma cells. Hybridization on total RNA extracted from dibutyryl-cAMP-treated NG108-15 cells shows a 5-fold increase of PDE5 9 kb mRNA: such an increase is not observed in N18TG2 although we observed a similar increase in the enzymatic activity of both cell lines. Our data demonstrate that PDE5 gene expression can be regulated by cAMP and suggest the existence of a complex regulatory system for PDE5 activity.  (+info)

Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. (3/318)

The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Sildenafil (Viagra), a specific PDE5 inhibitor, promotes penile erection by blocking the activity of PDE5, which causes cGMP to accumulate in the corpus cavernosum. In the present study, sildenafil, like other PDE5 inhibitors, stimulates cGMP binding to the allosteric sites of PDE5 by interacting at the catalytic site of this enzyme, but the drug does not compete with cGMP for binding at the allosteric sites. Both sildenafil and zaprinast are competitive inhibitors of PDE5, and double-inhibition analysis shows that these two inhibitors added together interact with the catalytic site of PDE5 in a mutually exclusive manner. After site-directed mutagenesis of each of 23 conserved amino acid residues in the catalytic domain of PDE5, the pattern of changes in the IC50 values for sildenafil or UK-122764 is similar to that found for zaprinast. However, among the three inhibitors, sildenafil exhibits the most similar pattern of changes in the IC50 to that found for the affinity of cGMP, implying similar interactions with the catalytic domain. This may explain in part the stronger inhibitory potency of sildenafil for wild-type PDE5 compared with the other inhibitors [sildenafil (Ki = 1 nM) > UK-122764 (Ki = 5 nM) > zaprinast (Ki = 130 nM)]. The affinity of each of these inhibitors for PDE5 is much higher than that of cGMP itself (Km = 2000 nM). It is concluded that residues such as Tyr602, His607, His643, and Asp754 may form important interactions for sildenafil in PDE5, but because these amino acids are conserved in all mammalian PDEs, the selectivity and potency of sildenafil is likely to be provided by a nonconserved residue or residues in the PDE5 catalytic domain.  (+info)

Improvement of mortality by long-term E4010 treatment in monocrotaline-induced pulmonary hypertensive rats. (4/318)

We investigated the effects of long-term treatment with a selective phosphodiesterase 5 inhibitor E4010, 4-(3-chloro-4methoxybenzyl)amino-1-(4-hydroxypiperidino)-6-phth alazin ecarbonitrile monohydrochloride, on the survival rate of rats with pulmonary hypertension induced by monocrotaline (MCT). After an s.c. injection of 40 mg/kg MCT (day 0), male Wistar rats of 4 weeks of age were divided into four groups. Vehicle-treated rats (control, n = 8) and MCT-treated rats (n = 32) were fed a commercial diet. E4010-treated rats were given a commercial diet containing 0.01% (E4010 0.01%, n = 32) and 0.1% (E4010 0.1%, n = 32) of E4010, respectively. At day 23, all rats in the control group and 28.1% of those in the MCT group (P <.01 versus control) were alive. Although the survival rate of E4010 0.01%-treated rats was not improved (50%) compared with MCT, those at 0.1% showed a significant difference (84. 4%, P <.01 versus MCT). For MCT rats (n = 9), right ventricle weight and the levels of plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, and cyclic AMP were higher compared with control (n = 8). In E4010 0.1%-treated rats (n = 27), the right ventricular hypertrophy was suppressed, and the increase in plasma cGMP level was amplified compared with MCT without any effects on plasma ANP, BNP, and cyclic AMP levels. Accordingly, we consider that the mechanism of action of E4010 may be related to the decreased pulmonary arterial pressure caused by the augmentation of pulmonary arterial relaxation through an ANP and/or BNP-cGMP system. These results suggest that E4010 will be useful for the treatment of pulmonary hypertension.  (+info)

Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases. (5/318)

We have reported alternative splice variants of cGMP-binding cGMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 and PDE5A2, which possess distinct N-terminal sequences. In this study, the DNA sequences corresponding to the unique N-terminal portions of PDE5A1 and PDE5A2 were shown to be tandemly located upstream of exons encoding the common region of PDE5A in both human and rat PDE5A genes. The presence of human PDE5A2 and rat PDE5A1 transcripts in lung was confirmed by reverse transcriptase-PCR. These results indicated that two variant forms of PDE5A exist in humans, canines and rats. We examined the tissue distribution of the two variants of human PDE5A in adult and fetal humans. The patterns of expression of the two alternatively spliced transcripts of human PDE5A in human tissues differed. Many putative regulatory elements including cAMP response elements were observed in the 5'-untranslated region and intron of the PDE5A gene. The levels of the PDE5A transcripts, especially the PDE5A2 transcripts, were increased by a cAMP analogue in cultured rat vascular smooth muscle cells, indicating that the PDE5A2 is an inducible variant of PDE5A in rats.  (+info)

Studies of the molecular mechanism of discrimination between cGMP and cAMP in the allosteric sites of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). (6/318)

The regulatory domain of the cGMP-binding cGMP-specific 3':5'-cyclic nucleotide phosphodiesterase (PDE5) contains two homologous segments of amino acid sequence that encode allosteric cyclic nucleotide-binding sites, referred to as site a and site b, which are highly selective for cGMP over cAMP. The possibility that the state of protonation in these sites contributes to cyclic nucleotide selectivity was investigated. The binding of cGMP or cAMP was determined using saturation and competition kinetics at pH values between 5.2 and 9.5. The total cGMP binding by PDE5 was unchanged by variation in pH, but the relative affinity for cGMP versus cAMP progressively decreased as the pH was lowered. Using site-directed mutagenesis, a conserved residue, Asp-289, in site a of PDE5 has been identified as being important for cyclic nucleotide discrimination in this site. It is proposed that deprotonation of Asp-289 enhances the number and strength of bonds formed with cGMP, while concomitantly decreasing the interactions with cAMP.  (+info)

Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta. (7/318)

1. The sensitivity of the soluble guanylate cyclase (sGC)-cyclic guanosine-3',5'-monophosphate (cyclic GMP) system to nitric oxide (NO) was investigated in mouse aorta from wild type (WT) and NO synthase (NOS) knockout (KO) animals. 2. The NO donor, spermine-NONOate (SPER-NO) was more potent in aortas from eNOS KO mice compared to WT (pEC50 7.30+/-0.06 and 6.56+/-0.04, respectively; n=6; P<0.05). In contrast, the non-NO based sGC activator, YC-1 was equipotent in vessels from eNOS WT and KO mice. The sensitivity of aortas from nNOS and iNOS KO animals to SPER-NO was unchanged. Forskolin (an adenylate cyclase activator), was equipotent in vessels from eNOS WT and KO animals. 3. The cyclic GMP analogue, 8-Br-cGMP was equipotent in eNOS WT and KO mice (pEC50 4. 38+/-0.04 and 4.40+/-0.05, respectively; n=5; P>0.05). Zaprinast (10-5 M) a phosphodiesterase type V (PDE V) inhibitor, had no effect on the response to SPER-NO in vessels from eNOS WT or KO mice. 4. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 3x10-4 M) increased the potency of SPER-NO in aortas from WT mice (pEC50 6. 64+/-0.02 and 7.37+/-0.02 in the absence and presence of L-NAME, respectively; n=4; P<0.05). 5. In summary, there is increased sensitivity of vessels from eNOS KO animals to NO. Cyclic AMP-mediated dilatation is unchanged, consistent with a specific up-regulation of sGC - cyclic GMP signalling. The functional activity of cyclic GMP-dependent protein kinase (G-kinase) and PDE V was also unchanged, suggesting that sGC is the site of up-regulation. These alterations in the sensitivity of the sGC - cyclic GMP pathway might represent a mechanism for the dynamic regulation of NO bioactivity.  (+info)

Impaired cerebral vasodilator responses to NO and PDE V inhibition after subarachnoid hemorrhage. (8/318)

Subarachnoid hemorrhage (SAH) is associated with impaired nitric oxide (NO)-mediated cerebral vasodilatation. We tested the hypothesis that SAH causes alterations in the production of, hydrolysis of, or responsiveness to cGMP in the rat basilar artery in vivo. Rats were injected with saline or autologous blood into the cisterna magna. Two days later, effects of vasoactive drugs on basilar artery diameter were examined using a cranial window preparation. Vasodilator responses to ACh, sodium nitroprusside (SNP), and low concentrations (+info)

Plus itPlus it
This cGMP effect on DRG axon branching is specific, because 8-bromoadenosine-3′,5′-cyclic monophosphate (8-Br-cAMP), an equivalent analog to activate the cAMP pathway, did not elicit the same effect (Fig. 1G-I). Neither the distribution nor the average number of branching points changed significantly in the 8-Br-cAMP-treated culture compared with the untreated one (Fig. 1N,P). Furthermore, YC-1, a small molecule that activates the soluble guanylyl cyclase (sGC) to produce cGMP (Galle et al., 1999), induced branch formation in a dose dependent manner, reaching a similar level as in the 8-Br-cGMP-treated culture (Fig. 1J-L,O,P). Conversely, Zaprinast, an inhibitor that prevents cGMP degradation by phosphodiesterase-5 (Dundore et al., 1993), also induced branching (data not shown).. We further examined several parameters to determine if the in vitro effect reflects the role of cGMP signaling in axon growth or branching. First, neurons from the control cultures had a total length (Lt) of 254 ± ...
http://www.jneurosci.org/content/29/5/1350
The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase - Enlighten:...The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase - Enlighten:...
MacPherson, M., Broderick, K., Graham, S., Day, J., Houslay, M., Dow, J. and Davies, S. (2004) The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase. Journal of Experimental Biology, 207, pp. 2769-2776. (doi:10.1242/jeb.01086) ...
http://eprints.gla.ac.uk/10462/
Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5...Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5...
In this article, we show that NO not only induces a rapid cGMP response in platelets and in aortic strips but also serves to alter the responsiveness of the cGMP cascade. In both models, the NO-induced cGMP response is biphasic and characterized by a very fast increase in cGMP, which amounts to a calculated peak concentration of ∼60 μM in platelets (see below). Subsequently, the concentration of cGMP declines rapidly, and it can be assumed that PDE activity has outcompeted cGMP synthesis. Thus, the biphasic cGMP accumulation profiles are indicative of a complex, thus far poorly understood interplay of cGMP-forming and -degrading activities.. The rapid desensitizing effect of NO is demonstrated by preincubating platelets or aortic strips, which reveals that the extent of the cGMP response is inversely related to the amount of NO present during the preincubation (Figs. 2 and 3 B). At high NO concentrations, the cGMP system becomes desensitized almost completely, whereas at low tissue ...
http://jcb.rupress.org/content/155/2/271
cenforce 150mg | Social Media SEOd
Cenforce (Sildenafil Citrate) falls under the class of medication known as a phosphodiesterase inhibitor. It shows it action by preventing the functioning of a PDE-5 enzyme of cGMP degradation in corpus cavernosum. In a sensually stimulated man, nitric oxide release occurs augmenting the level of cGMP. The enrich amount of cGMP causes vasodilation and relaxation […]. ...
http://socialmediaseod.com/tag/cenforce-150mg/page/6/
EHNA hydrochloride | CAS# 58337-38-5 | 2265 | BioVision, Inc.EHNA hydrochloride | CAS# 58337-38-5 | 2265 | BioVision, Inc.
EHNA is a selective inhibitor of the cGMP-specific phosphodiesterase (PDE2) (IC₅₀s = 0.8 and 2 μM from human and porcine myocardium, respectively, 3.5 μM in rat hepatocyte, and 5.5 μM in human platelet).
https://www.biovision.com/ehna-hydrochloride.html
Influence of a Prematuration Culture With a Phosphodiesterase-3 Inhibitor (PDE3-I) on Embryonic Aneuploidy Rate and...Influence of a Prematuration Culture With a Phosphodiesterase-3 Inhibitor (PDE3-I) on Embryonic Aneuploidy Rate and...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
https://clinicaltrials.gov/ct2/show/NCT00823420
ITI 214 - AdisInsightITI 214 - AdisInsight
Intra-Cellular Therapies is developing ITI 214, a phosphodiesterase type I (PDE1) inhibitor, as an orally administered treatment for cognitive impairment
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Phosphodiesterase type 4 inhibitors | definition of phosphodiesterase type 4 inhibitors by Medical dictionaryPhosphodiesterase type 4 inhibitors | definition of phosphodiesterase type 4 inhibitors by Medical dictionary
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TY - JOUR. T1 - Long-acting phosphodiesterase-5 inhibitor, tadalafil, induces sustained cardioprotection against lethal ischemic injury. AU - Ahmad, Nauman. AU - Wang, Yigang. AU - Ali, Ailia K.. AU - Ashraf, Muhammad. PY - 2009/7/1. Y1 - 2009/7/1. N2 - The ability of pharmacological preconditioning mimetics to confer long-lasting and sustained cardioprotection may be a logical criterion to develop a drug that can be used clinically for cardioprotection. We propose here that the use of long-acting phosphodiesterase-5 inhibitor, tadalafil, may confer sustained cardioprotection against ischemia. Tadalafil (5 mg/kg) was administered orally to male C57B/6J mice (n = 6 in each treatment subgroup at each time point studied). Hearts were isolated and subjected to 40 min of ischemia and 30 min of reperfusion on Langendorffs apparatus at 1, 12, 24, 36, 48, 60, 72, and 108 h after tadalafil administration. In 1- to 48-h subgroups, tadalafil was given once at 0 h only. In 60- and 72-h subgroups, tadalafil ...
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A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a drug used to block the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. These drugs are used in the treatment of erectile dysfunction and were the first effective oral treatment available for the condition. Because PDE5 is also present in the arterial wall smooth muscle within the lungs, PDE5 inhibitors have also been explored for the treatment of pulmonary hypertension, a disease in which blood vessels in the lungs become overloaded with fluid, usually as a result of failure of the right ventricle of the heart. PDE5 inhibitors such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) are clinically indicated for the treatment of erectile dysfunction. Sildenafil and tadalafil are also indicated for the treatment of pulmonary hypertension. Sildenafil, the prototypical PDE5 inhibitor, was ...
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http://medreviews.com/journal/reviews-in-cardiovascular-medicine/vol/15/no/2/therapeutic-potentials-phosphodiesterase-5-inhibitors-in-cardiovascular-disease
Reduced Vascular Nitric Oxide-cGMP Signaling Contributes to Adipose Tissue Inflammation During High-Fat Feeding |...Reduced Vascular Nitric Oxide-cGMP Signaling Contributes to Adipose Tissue Inflammation During High-Fat Feeding |...
Methods and Results-Relative to mice fed a low-fat diet, an HF diet markedly reduced phospho-eNOS and phospho-vasodilator-stimulated phosphoprotein (phospho-VASP), markers of vascular NO signaling. Expression of proinflammatory cytokines was increased in adipose tissue of eNOS−/− mice. Conversely, enhancement of signaling downstream of NO by phosphodiesterase-5 inhibition using sildenafil attenuated HF-induced proinflammatory cytokine expression and the recruitment of macrophages into adipose tissue. Finally, we implicate a role for VASP, a downstream mediator of NO-cGMP signaling in mediating eNOS-induced antiinflammatory effects because VASP−/− mice recapitulated the proinflammatory phenotype displayed by eNOS−/− mice.. ...
http://atvb.ahajournals.org/content/early/2011/09/08/ATVBAHA.111.236554
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cGMP signals modulate cAMP levels in a compartment-specific manner to regulate catecholamine-dependent signaling in cardiac...
RATIONALE: cAMP and cGMP are intracellular second messengers involved in heart pathophysiology. cGMP can potentially affect cAMP signals via cGMP-regulated phosphodiesterases (PDEs). OBJECTIVE: To study the effect of cGMP signals on the local cAMP response to catecholamines in specific subcellular compartments. METHODS AND RESULTS: We used real-time FRET imaging of living rat ventriculocytes expressing targeted cAMP and cGMP biosensors to detect cyclic nucleotides levels in specific locales. We found that the compartmentalized, but not the global, cAMP response to isoproterenol is profoundly affected by cGMP signals. The effect of cGMP is to increase cAMP levels in the compartment where the protein kinase (PK)A-RI isoforms reside but to decrease cAMP in the compartment where the PKA-RII isoforms reside. These opposing effects are determined by the cGMP-regulated PDEs, namely PDE2 and PDE3, with the local activity of these PDEs being critically important. The cGMP-mediated modulation of cAMP also affects
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Background: Phosphodiesterase-5 (PDE5) inhibitors reduce infarct size and protect against early LV dysfunction after myocardial infarction (MI) in mice. The effect of sustained administration of PDE5-inhibitors on long-term survival and development of heart failure after MI has not been studied.. Methods: Ten weeks after MI, induced by permanent LAD ligation, mice (n=53) were randomized to receive the PDE5-specific inhibitor sildenafil, (SIL 100 mg/kg/day via drinking water) or placebo. After 1 year, LV function and remodeling were measured using cine-MRI (9.4T Bruker) and invasive pressure-volume (P-V) catheterization. Heart weight normalized to tibia length (HW/TL) and cardiomyocyte (CM) width in the MI border zone were measured. In addition, we investigated the effect of SIL on LV remodeling in mice with overexpression of PDE5 in cardiac myocytes (PDE5TG, n=53).. Results: Survival at 1y was 34% in placebo but markedly greater following SIL (50%). SIL attenuated global LV dysfunction measured ...
http://circ.ahajournals.org/content/122/Suppl_21/A21305
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Characterization of tandem GAF domains of phosphodiesterases | BMC Pharmacology | Full TextCharacterization of tandem GAF domains of phosphodiesterases | BMC Pharmacology | Full Text
In PDE10 the allosteric activator is cAMP whereas in all other mammalian PDEs of this sub-family cGMP serves as an activator. Mutational studies indicated that the PDE 10 GAF tandem domain signals via its GAF-B region like PDE2 whereas the GAF tandem of PDE5 signals via its GAF-A region. We generated hybrid chimeras between the GAF tandems of PDE 5, binding cGMP, and PDE 10, binding cAMP, in order to investigate whether we would obtain a GAF tandem capable of signalling by cGMP via GAF A and by cAMP via GAF B. This was not unequivocally accomplished. However, we demonstrate that the mode of signalling appears to be strongly affected by the source of the α-helix which connects the GAF-A and GAF-B regions. A hybrid construct comprised of the N-terminal and GAF-A from PDE5 and the linker and GAF-B from PDE10 could be stimulated by cAMP and, to a lesser extent, by cGMP. However, a similar construct in which the linker between GAF-A (from PDE5) and B (from PDE10) was from the PDE 5 was unresponsive ...
https://bmcpharma.biomedcentral.com/articles/10.1186/1471-2210-7-S1-S1
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Architecture of the PDE5-Vardenafil Structure. The enzyme of the PDE5A1 catalytic domain used in these studies was fully active and exhibited kinetic properties (kcat, Km) similar to those for the full-length PDE5A1 (Wang et al., 2006). The structure of the PDE5A1 catalytic domain (residues 535-860) in complex with vardenafil consists of 15 α-helices (Fig. 2). Most of the residues in the PDE5A1-vardenafil cocrystal had solid electron density and were traced without ambiguity. Residues 660 to 672 and 792 to 806, which are parts of the H- and M-loops, lacked electron density and were disordered. The superimposition of PDE5A1-vardenafil over other previously determined PDE5A1 structures (Huai et al., 2004; Wang et al., 2006) yielded root-mean-square deviations of 0.49, 0.54, 0.51, and 0.47 Å, respectively for Cα atoms of 270 comparable residues (536-657, 686-787, and 813-859) of the unliganded PDE5A1 and its complexes with IBMX, icarisid II, and sildenafil, indicating the overall similarity ...
http://molpharm.aspetjournals.org/content/73/1/104
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https://sr.wikipedia.org/wiki/CGMP-specifi%C4%8Dna_fosfodiesteraza,_tip_5
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PDE1CPDE1C
2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... 2006). "Subcellular localization and regulation of type-1C and type-5 phosphodiesterases". Biochem. Biophys. Res. Commun. 341 ( ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ... cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. GRCh38: Ensembl release 89: ...
https://en.wikipedia.org/wiki/PDE1C
CGMP-specific phosphodiesterase type 5CGMP-specific phosphodiesterase type 5
"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
Neuronal calcium sensor-1Neuronal calcium sensor-1
... cyclic nucleotide phosphodiesterases ARF1 (ADP Ribosylation factor 1) A type (Kv4.3; Shal-related subfamily, member 3) voltage- ... The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the ... type III phosphatidylinositol 4-kinase β) IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment ... 5 (5): e10534. Bibcode:2010PLoSO...510534H. doi:10.1371/journal.pone.0010534. PMC 2866544. PMID 20479890. Pongs O, Lindemeier J ...
https://en.wikipedia.org/wiki/Neuronal_calcium_sensor-1
PDE4APDE4A
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
Cyclic nucleotide phosphodiesteraseCyclic nucleotide phosphodiesterase
"Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a ... cyclic-nucleotide phosphodiesterases in rod cells are oligomeric, made up of two heavy catalytic subunits, α (90 kDa) and β (85 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacological Reviews. 58 (3): 488-520. doi: ...
https://en.wikipedia.org/wiki/Cyclic_nucleotide_phosphodiesterase
Cyclic nucleotideCyclic nucleotide
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
Discovery and development of phosphodiesterase 5 inhibitorsDiscovery and development of phosphodiesterase 5 inhibitors
Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine ... "Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality". Heart. 102 ( ...
https://en.wikipedia.org/wiki/Discovery_and_development_of_phosphodiesterase_5_inhibitors
Cyclic di-AMPCyclic di-AMP
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
Pharmacology of antidepressantsPharmacology of antidepressants
... by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). One manifestation of depression is an ... a type of glutamate receptor - produces rapid (within 2 hours), robust and sustained (lasting for up to a fortnight) ... "Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor ... system induced by different types of chronic but not acute antidepressant treatment, including serotonin and norepinephrine ...
https://en.wikipedia.org/wiki/Pharmacology_of_antidepressants
PhosphodiesterasePhosphodiesterase
"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
Benjamin Weiss (scientist)Benjamin Weiss (scientist)
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)
TNF inhibitorTNF inhibitor
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 ... Several 5-HT2A agonist hallucinogens including (R)-DOI, TCB-2, LSD and LA-SS-Az have unexpectedly also been found to act as ...
https://en.wikipedia.org/wiki/TNF_inhibitor
OligodendrocyteOligodendrocyte
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
Phosphodiesterase 3Phosphodiesterase 3
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
Phosphodiesterase-4 inhibitorPhosphodiesterase-4 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
PDE4BPDE4B
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". ... "Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)". Swerdlow, Neal R. ( ...
https://en.wikipedia.org/wiki/PDE4B
PDE9APDE9A
1998). "Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: ... "Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential ... cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene. The protein encoded by this gene ... "Entrez Gene: PDE9A phosphodiesterase 9A". Verhoest PR, Fonseca KR, Hou X, et al. (2012). "Design and discovery of 6-[(3S,4S)-4- ...
https://en.wikipedia.org/wiki/PDE9A
PDE8BPDE8B
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. " ... cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by the PDE8B gene. GRCm38: Ensembl release 89: ...
https://en.wikipedia.org/wiki/PDE8B
Cyclic adenosine monophosphateCyclic adenosine monophosphate
... 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 ... such as cyclic adenosine monophosphate, cyclic AMP). Cyclic AMP is synthesized from ATP by adenylate cyclase located on the ...
https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate
PentoxifyllinePentoxifylline
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
GAF domainGAF domain
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
PDE6BPDE6B
"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 ... cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 ...
https://en.wikipedia.org/wiki/PDE6B
CGAS-STING cytosolic DNA sensing pathwayCGAS-STING cytosolic DNA sensing pathway
cGAMP was found to be much more potent than other cyclic di-nucleotides (c-di-GMP and c-di-AMP). cGAMP was shown to ... STING's general role as an adapter molecule in the cytosolic DNA-type 1 IFN response across cell types has been suggested 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 ...
https://en.wikipedia.org/wiki/CGAS–STING_cytosolic_DNA_sensing_pathway
P19 cellP19 cell
Cyclic-nucleotide 3'-phosphodiesterase. Moreover, oligodendrocytes also developed and migrated into fiber bundles in mice when ... Using doses between 1 μM to 3 μM of RA can generate neurons as the most abundant cell type. Neurons under this treatment ... The cell line is pluripotent and can differentiate into cell types of all three germ layers. Also, it is the most characterized ... At concentration of 0.5-1% DMSO induced P19 cells to aggregate and process mesodermal and endodermal cell types. The cellular ...
https://en.wikipedia.org/wiki/P19_cell
Enzyme inhibitorEnzyme inhibitor
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
Caffeine-induced anxiety disorderCaffeine-induced anxiety disorder
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
Phosphodiesterase inhibitorPhosphodiesterase inhibitor
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
PDE5 inhibitorPDE5 inhibitor
Differential Activation and Inhibition of the Multiple Forms of Cyclic Nucleotide Phosphodiesterase. Advances in Cyclic ... A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug that works by blocking the degradative action of ... Fertel R, Weiss B (July 1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". ... Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ...
https://en.wikipedia.org/wiki/PDE5_inhibitor
List of EC numbers (EC 3)List of EC numbers (EC 3)
... 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 ... type I site-specific deoxyribonuclease EC 3.1.21.4: type II site-specific deoxyribonuclease EC 3.1.21.5: type III site-specific ... phosphodiesterase * EC 3.1.4.59: cyclic-di-AMP phosphodiesterase * EC 3.1.4.60: pApA phosphodiesterase * EC 3.1.4.61: cyclic 2, ... 2-cyclic phosphate phosphodiesterase * EC 3.1.4.56: 7,8-dihydroneopterin 2′,3′-cyclic phosphate phosphodiesterase EC 3.1.4.57: ...
https://en.wikipedia.org/wiki/List_of_EC_numbers_(EC_3)
PDE1PDE1
Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... The catalytic domains of phosphodiesterase 1 (and other types of phosphodiesterases) have three helical subdomains: an N- ... Kakkar R, Raju RV, Sharma RK (July 1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)". Cell. Mol. Life ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ...
https://en.wikipedia.org/wiki/PDE1
Sperm chemotaxisSperm chemotaxis
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
PDE4DPDE4D
"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 ... Zhang HT (2009). "Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs". Current ...
https://en.wikipedia.org/wiki/PDE4D
Κ-opioid receptorΚ-opioid receptor
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
RetinaRetina
... 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
Biochemical cascadeBiochemical cascade
"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
CaffeineCaffeine
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 ... The ICD-11 includes caffeine dependence as a distinct diagnostic category, which closely mirrors the DSM-5's proposed set of ... Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase. Caffeine is a bitter, white ...
https://en.wikipedia.org/wiki/Caffeine
MutationMutation
... the first letter represents the wild-type nucleotide, and the second letter represents the nucleotide that replaced the wild ... 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) - The ... 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
Photoreceptor cellPhotoreceptor cell
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
Retinitis pigmentosa GTPase regulatorRetinitis pigmentosa GTPase regulator
... 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
TransducinTransducin
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
Tubulin alpha-1A chainTubulin alpha-1A chain
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
Guanylate cyclaseGuanylate cyclase
Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ... There are membrane-bound (type 1, guanylate cyclase-coupled receptor) and soluble (type 2, soluble guanylate cyclase) forms of ... Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on ... cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and ...
https://en.wikipedia.org/wiki/Guanylate_cyclase
ParaxanthineParaxanthine
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
WO2004108726A1 - 2-SUBSTITUTED PHENYL-5,7-DIALKYL-3,7-DIHYDROPYRROLE [2,3-d] PYRIMIDINE-4-ONE DERIVATIVES, THE PREPARATION AND...
... especially erectile dysfunction of male and the diseases in which the function of phospholipase 5 (cGMP PDE5) is involved. ... 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2 * 108010037581 Type 5 Cyclic ... Nucleotide Phosphodiesterases Proteins 0.000 description 2 * 238000010521 absorption reaction Methods 0.000 description 2 ... ZOOGRGPOEVQQDX-UUOKFMHZSA-N Cyclic guanosine monophosphate Chemical compound data:image/svg+xml;base64, ...
https://patents.google.com/patent/WO2004108726A1/en
Galectin-3 in heart failure with preservedejection fraction. A RELAX trial substudy (phosphodiesterase-5 inhibition to improve...
Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p= 0.53). Conclusions ... Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p= 0.53). Conclusions ... Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p= 0.53). Conclusions ... Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p= 0.53). Conclusions ...
https://mayoclinic.pure.elsevier.com/en/publications/galectin-3-in-heart-failure-with-preservedejection-fraction-a-rel
DeCSDeCS
Cyclic Nucleotide Phosphodiesterases, Type 5 - Preferred Concept UI. M0295388. Scope note. A cyclic nucleotide ... Phosphodiesterase 5A Phosphodiesterase 5A, cGMP Specific Phosphodiesterase 5A, cGMP-Specific Phosphodiesterase Type 5 ... Cyclic Nucleotide Phosphodiesterases, Type 5 Descriptor Spanish: Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 Spanish from ... Phosphodiesterase 5A. Phosphodiesterase 5A, cGMP Specific. Phosphodiesterase 5A, cGMP-Specific. Phosphodiesterase Type 5. ...
https://decs.bvsalud.org/en/ths/resource/?id=52680
Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: Pathophysiology and...
... with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition. Methods: ... Results: Major mechanisms contributing to LUTS include: reduced nitric oxide/cyclic guanosine monophosphate signaling; ... with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition. Methods: ... with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition. Methods: ...
https://utsouthwestern.pure.elsevier.com/en/publications/tadalafil-for-the-treatment-of-lower-urinary-tract-symptoms-secon
Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC by Vanesa D. Ramseyer, Pablo A. Ortiz et al."Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC" by Vanesa D. Ramseyer, Pablo A. Ortiz et al.
ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated inhibition of NKCC2 ... Angiotensin II; Animals; Cyclic CMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelin-1; Hypertension; Loop ... In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated ... Phosphodiesterase 5 Inhibitors; Rats; Rats, Sprague-Dawley; Solute Carrier Family 12, Member 1; Vardenafil Dihydrochloride ...
https://scholarlycommons.henryford.com/hypertension_articles/45/
Erectile Dysfunction Medication: Phosphodiesterase-5 Enzyme Inhibitors, Vasodilators, AndrogensErectile Dysfunction Medication: Phosphodiesterase-5 Enzyme Inhibitors, Vasodilators, Androgens
... tissue distributions and functions but that all exert their effect by lowering intracellular levels of cyclic nucleotides, such ... The types of medications can be divided into oral, topical, injectable, and intraurethrally inserted. Phosphodiesterase type 5 ... Phosphodiesterase-5 Enzyme Inhibitors. Class Summary. At least seven phosphodiesterase (PDE) classes are known, many with ... Identifying patients with type 2 diabetes with a higher likelihood of erectile dysfunction: the role of the interaction between ...
https://emedicine.medscape.com/article/444220-medication
Pesquisa | Portal Regional da BVSPesquisa | Portal Regional da BVS
... that are responsible for the hydrolysis of cyclic nucleotides. Phosphodiesterase type 5 (PDE5) is a cGMP-specific PDE, broadly ... Methods: Clonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath- ... Interestingly, NO donors and cGMP analogs increase the capacity of anti-platelet drugs targeting the purinergic receptor type Y ... BACKGROUND: The small GTPase Rap1 and its guanine nucleotide exchange factor, CalDAG-GEFI (CDGI), are critical for platelet ...
https://pesquisa.bvsalud.org/portal/?lang=pt&q=au:Stefanini,+Lucia
100-61-8 | MFCD00008283 | N-Methylaniline
Title: Cyclic nucleotide phosphodiesterase type 4 inhibitors: evaluation of pyrazolo[1,5-a]-1,3,5-triazine ring system as an ... bisphosphate C-nucleotide analogues as the first reported in vivo stable P2Y(1)-receptor antagonists.. Journal: The Journal of ... Title: A general approach toward the synthesis of C-nucleoside pyrazolo[1,5-a]-1,3,5-triazines and their 3,5- ... Title: Effect of additives on photodegradation of 1,3,5-trichlorobenzene in aqueous surfactant solutions.. Journal: Journal of ...
https://www.aablocks.com/prod/100-61-8
Intraspinal Transplantation of Autologous Neurogenically-Induced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of...Intraspinal Transplantation of Autologous Neurogenically-Induced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of...
Publication types * Research Support, Non-U.S. Govt MeSH terms * 2,3-Cyclic-Nucleotide Phosphodiesterases / analysis ... At the 4th month, gait score had improved 1 score in 5 cases, and one score progress was recorded in proprioception and ...
https://pubmed.ncbi.nlm.nih.gov/26242341/
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs.bvs.br/I/dcsnew2008.txt
Raimond L. Winslow - PublicationsRaimond L. Winslow - Publications
Roles of Phosphodiesterases in Cyclic Nucleotide Cross-Talk in Cardiac Myocytes Biophysical Journal. 108: 260a. DOI: 10.1016/J. ... Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type Calcium Channel regulation. Journal of ... Roles of phosphodiesterases in the regulation of the cardiac cyclic nucleotide cross-talk signaling network. Journal of ... Regulation of the Cardiac L-Type Calcium Channel by the Cyclic Nucleotide Cross-Talk Signaling Network Biophysical Journal. 110 ...
https://academictree.org/compbio/publications.php?pid=49117
June | 2018 | Hif signaling
2 type 2 diabetes,3 Cyclic nucleotide phosphodiesterase hypertension,4 and certain cancers.5 Although many related genes and ... None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. This ... Of these 23 patients, 6 with borderline low VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians, ... Results: Among 55 cirrhotic drivers with MHE [males, median age 53 years (range 30-60)], 7 (12.7%) reported any type of ...
https://hif-signaling.com/index.php/2018/06/
Functional properties and cell type specific distribution of Ih channels in leech neurons | Journal of Experimental Biology |...Functional properties and cell type specific distribution of Ih channels in leech neurons | Journal of Experimental Biology |...
Effect of cyclic nucleotides on Ih. (A,C) Ii (open symbols) and ISS (closed symbols) in the presence (circles) and absence ( ... or the phosphodiesterase inhibitor, IBMX (each 1 mmol l-1), the Ih channels of leech P neurons were half-maximally activated at ... Effect of cyclic nucleotides on Ih. (A,C) Ii (open symbols) and ISS (closed symbols) in the presence (circles) and absence ( ... A hyperpolarization-activated, cyclic nucleotide-gated (Ih-like) cationic current and HCN gene expression in renal inner ...
https://journals.biologists.com/jeb/article/215/2/227/11079/Functional-properties-and-cell-type-specific
TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. - Oxford Neuroscience
... beta-arrestin in complex with cAMP-specific phosphodiesterase 4 (PDE4) was recruited to lipid rafts which down-regulated cAMP ... Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Cyclic Nucleotide Phosphodiesterases, Type 4, Humans, Lymphocyte Activation, ... TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. ... TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. ...
https://www.neuroscience.ox.ac.uk/publications/55997?e6df861c-9f08-11ed-a592-061ab7f93640
S-EPMC6129132 - Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease. -...
Both inhibitors augment cyclic guanosine monophosphate (cGMP) to activate protein kinase G, with PDE5-I regulating nitric oxide ... Here we contrast 2 closely related therapies, inhibitors of phosphodiesterase type 5 or type 9 (PDE5-I, PDE9-I), given to mice ... Myocardial Phosphodiesterases and Their Role in cGMP Regulation.. Project description:Cyclic nucleotide phosphodiesterases ... Here we contrast 2 closely related therapies, inhibitors of phosphodiesterase type 5 or type 9 (PDE5-I, PDE9-I), given to mice ...
https://www.omicsdi.org/dataset/biostudies/S-EPMC6129132
Code System Concept
Cyclic-nucleotide phosphodiesterase Active Synonym false false 3721239018 3,5-cyclic-nucleotide phosphodiesterase Active ... Designation Type PHIN Preferred Term Flag Code Flag 10896010 3,5- ... cyclic-nucleotide phosphodiesterase (substance). Code System Preferred Concept Name. 3,5-cyclic-nucleotide phosphodiesterase ...
https://phinvads.cdc.gov/vads/ViewCodeSystemConcept.action?oid=2.16.840.1.113883.6.96&code=5950004
Marine Drugs | Free Full-Text | Yessotoxin, a Promising Therapeutic ToolMarine Drugs | Free Full-Text | Yessotoxin, a Promising Therapeutic Tool
... cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review ... The levels of cyclic nucleotides are regulated by phosphodiesterases (PDEs). These are a group of isozyme families with ... This type of paper provides an outlook on future directions of research or possible applications. ... Fernandez-Araujo, A.; Alfonso, A.; Vieytes, M.R.; Botana, L.M. Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered ...
https://www.mdpi.com/1660-3397/14/2/30
PDE1B Antibody (5B6) (H00005153-M01): Novus BiologicalsPDE1B Antibody (5B6) (H00005153-M01): Novus Biologicals
presumed 63kDa form of the type 1 cyclic nucleotide phosphodiesterase familyknown as PDE1B ... Cyclic nucleotides are hydrolyzed and compartmentalized by a family of enzymes called phosphodieterases. In mammals at least 11 ... Distinct metabolism of cyclic adenosine monophosphate in regulatory and helper CD4(+) T cells. Mol Immunol. 2009 Nov 23. [PMID ...
https://www.novusbio.com/products/pde1b-antibody-5b6_h00005153-m01
Br. J. Cancer (1981) 43, 669Br. J. Cancer (1981) 43, 669
We feel therefore that the mechanism of sensitization by MX does not relate to either effects on cyclic nucleo- tide metabolism ... In comparing these types of experiment it would appear that the level of MX used is critical. In all our experiments a slight ... On the other hand, it is also well established that MX, especially caffeine, can inhibit the phos- phodiesterases (Beavo et al ... Some evidence against such a role for cyclic nucleotides has been published (Ehmann et al., 1976) but only biophysical data ...
https://stacks.cdc.gov/view/cdc/22954/cdc_22954_DS5.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2014.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2013.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2018.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2012.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2008.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2010.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2020.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2015.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2017.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2011.bvsalud.org/I/dcsnew2008.txt
NEW (2008) DeCS DESCRIPTORS WITH SCOPE NOTES (UNIT RECORD FORMAT; 21/02/2008
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE 1984-2007 BX - Cyclic Nucleotide Phosphodiesterases, Type I MH - Cyclic Nucleotide ... 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 - ... HN - 2008 MH - Cyclic Nucleotide Phosphodiesterases, Type 1 UI - D054677 MN - D08.811.277.352.640.150.100 MN - D08.811.277.352. ...
https://decs2009.bvsalud.org/I/dcsnew2008.txt
InhibitorsPDE5Guanosine monophosphateCalmodulin-dependentProteinMetabolismSpecificityInhibitionEnzymesEncodesPeptideInhibits2020Erectile DysfunctionMeshHumansPutativeAntibodyMembraneSuperfamilyKinasePotentiatesRegulationMutationsVariantsClinicalReceptorsSmooth muscleProteinsSpeciesCatalyticCalciumMechanismsSignificanceMoleculesHuman
Inhibitors5
  • Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p= 0.53). (elsevier.com)
  • Phosphodiesterase type 5 (PDE5) inhibitors are the principal oral agents used in ED. (medscape.com)
  • Here we contrast 2 closely related therapies, inhibitors of phosphodiesterase type 5 or type 9 (PDE5-I, PDE9-I), given to mice subjected to sustained cardiac pressure overload (PO). (omicsdi.org)
  • Both inhibitors augment cyclic guanosine monophosphate (cGMP) to activate protein kinase G, with PDE5-I regulating nitric oxide (NO) and PDE9-I natriuretic peptide-dependent signaling. (omicsdi.org)
  • Phosphodiesterase-3 enzyme (PDE-3) inhibitors suppress megakaryocyte maturation, and thereby decrease platelet counts without affecting other hematopoietic cell lines. (medscape.com)
PDE56
  • This manuscript reviews the published literature describing the pathophysiology of male LUTS, with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition. (elsevier.com)
  • In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. (henryford.com)
  • Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. (omicsdi.org)
  • Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-induced PDE5 phosphorylation. (omicsdi.org)
  • cGMP-specific, cGMP-binding phosphodiesterase (PDE5) regulates such physiological processes as smooth muscle relaxation and neuronal survival. (omicsdi.org)
  • In vitro anticoagulants have shown that the penis of tadalafil is more likely on PDE5 than on other phosphodiesterases. (betterdad.com)
Guanosine monophosphate1
  • PDEs are a diverse family of enzymes that have different tissue distributions and functions but that all exert their effect by lowering intracellular levels of cyclic nucleotides, such as cyclic guanosine monophosphate (cGMP). (medscape.com)
Calmodulin-dependent3
  • In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. (drugbank.com)
  • Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. (drugbank.com)
  • Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion. (ouhsc.edu)
Protein7
  • Upon T cell activation of human peripheral blood T cells, we found that the majority of cAMP was generated in T cell lipid rafts followed by activation of protein kinase A. However, upon TCR and CD28 coligation, beta-arrestin in complex with cAMP-specific phosphodiesterase 4 (PDE4) was recruited to lipid rafts which down-regulated cAMP levels. (ox.ac.uk)
  • Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. (mdpi.com)
  • P. Banky, L. Huang, and S. S. Taylor , Dimerization/docking domain of the type Ia regulatory subunit of cAMP-dependent protein kinase. (inserm.fr)
  • Catalyzing the conversion of atp to cyclic adenosine- degradation or recycled to the, testosterone augmentation and a highly uneven men s sised that masculinity too is comparable to the elites of latin kind of white imperial revolution that removed alarmed at what anatomical level is the recommended dietary allowance for protein cyclase. (gatech.edu)
  • Growth factor receptor-bound protein 14: a new modulator of photoreceptor-specific cyclic-nucleotide-gated channel. (ouhsc.edu)
  • expressed in middle/late meiosis,IV" YDR525W 1 5 7 YDR525W "Ydr525wp,IV" YDR526C 1 5 8 YDR526C "Ydr526cp,IV" YER187W 1 5 9 YER187W "similar to killer toxin,V" YER188W 1 5 10 YER188W "Yer188wp,V" YER190W 1 5 11 YER190W "Yrf1-2p,V" YFL002C 1 5 12 YFL002C "ATP-dependent RNA helicase,VI" YFL002W-B 1 5 13 YFL002W-B "TyA gag protein. (davidson.edu)
  • XIII" YMR047C 3 13 3 YMR047C "Nuclear pore complex protein that is member of GLFG repeat-containing family of nucleoporins and is,XIII" YMR049C 3 13 4 YMR049C "Ymr049cp,XIII" YMR051C 3 13 5 YMR051C "TyA Gag protein. (davidson.edu)
Metabolism1
  • The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation. (nature.com)
Specificity1
  • element that accounts for guanine nucleotide specificity. (cornell.edu)
Inhibition4
  • A RELAX trial substudy (phosphodiesterase-5 inhibition to improve clinical status and exercise capacity in diastolic heartfailure). (elsevier.com)
  • Methods: Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. (elsevier.com)
  • Conclusions: In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. (elsevier.com)
  • Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. (drugbank.com)
Enzymes3
  • Cyclic nucleotides are hydrolyzed and compartmentalized by a family of enzymes called phosphodieterases. (novusbio.com)
  • CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. (drugbank.com)
  • Trl1 enzymes are found in all human fungal pathogens and are promising targets for antifungal drug discovery because their domain compositions and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme. (cornell.edu)
Encodes2
  • The Rv0805 gene from Mycobacterium tuberculosis encodes a 3',5'-cyclic nucleotide phosphodiesterase: biochemical and mutational analysis. (rhea-db.org)
  • Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kucinski I, Ginalski K, Dziembowski A. C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3' end modification. (medlineplus.gov)
Peptide1
  • In contrast, recent studies have shown that C-type Natriuretic Peptide (CNP) is an important anabolic regulator of cartilage growth, and loss-of-function mutations in the human CNP receptor gene cause dwarfism. (biomedcentral.com)
Inhibits3
  • however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. (drugbank.com)
  • Anagrelide is a phosphodiesterase-3 enzyme (PDE-3) inhibitor that inhibits platelet aggregation. (medscape.com)
  • It inhibits cyclic nucleotide phosphodiesterase and the release of arachidonic acid from phospholipase, possibly by inhibiting phospholipase A2. (medscape.com)
20201
Erectile Dysfunction2
  • centrifuged inorganic molecules, major contributors to erectile problems compared with gation and thrombus into this ment usually given by intramuscular injection testis towards the periphery.5 blood slowly diffuses from the category, represents 18.6% of this is due to the venous system causes ejaculation and pathophysiology of erectile dysfunction (ed). (psm.edu)
  • You have to limited the type of erectile dysfunction pill you want based on your usage. (betterdad.com)
Mesh1
  • Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. (musc.edu)
Humans1
  • Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in humans. (rhea-db.org)
Putative1
  • 5 × 10 −8 ) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. (nature.com)
Antibody1
  • In a separate cohort, we retrospectively analyzed the effect of aspirin on the antibody response 1 and 5 months after BNT162b2 vaccination. (bvsalud.org)
Membrane1
  • Light-induced tyrosine phosphorylation of rod outer segment membrane proteins regulate the translocation, membrane binding and activation of type II a phosphatidylinositol-5-phosphate 4-kinase. (ouhsc.edu)
Superfamily1
  • Cyclic nucleotide phosphodiesterases comprise an 11-member superfamily yielding near 100 isoform variants that hydrolyze cAMP or cGMP to their respective 5'-monophosphate form. (omicsdi.org)
Kinase1
  • 1%, selleck kinase inhibitor regardless of the typing method used. (raf-signal.com)
Potentiates1
  • TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. (ox.ac.uk)
Regulation1
  • Myocardial Phosphodiesterases and Their Role in cGMP Regulation. (omicsdi.org)
Mutations1
  • None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. (hif-signaling.com)
Variants1
  • Figure 3: Comparison of single-marker P values for the 5% FDR variants in the published CARDIoGRAMplusC4D 1000 Genomes-imputed CAD GWAS meta-analysis and the current FDR-based analysis. (nature.com)
Clinical1
  • Data entry was repeated on the 5 % of clinical trial and observational reports that provided the largest number of endpoints. (raf-signal.com)
Receptors1
  • There are three main receptors on the cells for HTLV-1 including neuropilin, glucose transporter 1 (GLUT-1), and heperan sulfate proteoglycan [ 5 ]. (biomedcentral.com)
Smooth muscle2
  • It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. (drugbank.com)
  • Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. (drugbank.com)
Proteins1
  • The differentiation of mesenchymal cells into chondroblasts is regulated by the activity of the Sox9 transcription factor, which controls the expression of principal genes encoding the extracellular matrix proteins of cartilage, such as collagen type II and aggrecan [ 4 ]. (biomedcentral.com)
Species2
  • The hyperpolarisation-activated cation current ( I h ) has been described in many vertebrate and invertebrate species and cell types. (biologists.com)
  • the spermatic cord, and the dominant routes in the pri- macy issue and/or how long he lasts is obviously going to become supericial (1) and deep (5) venous pattern (fig. Ultrastructural oxygen species production in men. (psm.edu)
Catalytic1
  • Binding of cGMP to the GAF-B domain of phosphodiesterase 2A allosterically activates catalytic activity. (mssm.edu)
Calcium3
  • There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. (drugbank.com)
  • T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. (drugbank.com)
  • The pharmacologic significance of T-type calcium channel blockade is unknown. (drugbank.com)
Mechanisms1
  • This has involved the study of noradrenergic mechanisms in the actions of antidepressant drugs and of cyclic nucleotide phosphodiesterases as potential targets for novel antidepressant, anxiolytic, and memory-enhancing drugs. (buffalo.edu)
Significance1
  • This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold 2 , thus providing strong support that the remaining loci identified by FDR represent genuine signals. (nature.com)
Molecules2
  • A possible strategy to inhibit undesired PPIs is to design small organic molecules binding in the zone of interactions and the increasing number of such recent success stories prove it [ 3 - 5 ]. (biomedcentral.com)
  • RNA exonucleases cut off (cleave) building blocks called nucleotides one at a time from molecules of RNA (a chemical cousin of DNA). (medlineplus.gov)
Human3
  • Human T-cell Leukemia Virus type-1 (HTLV-1) is a retrovirus that causes two diseases including Adult T-cell Leukemia/Lymphoma (ATLL cancer) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP, a neurodegenerative disease) after a long latency period as an asymptomatic carrier (AC). (biomedcentral.com)
  • Full-length cDNAs of human cyclic nucleotide phosphodiesterase 8B (PDE8B) were isolated. (rhea-db.org)
  • Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterasis isozymes. (comoceviche.com)