Cyclic Nucleotide Phosphodiesterases, Type 1: A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Cyclic Nucleotide Phosphodiesterases, Type 4: A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.Cyclic Nucleotide Phosphodiesterases, Type 3: A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.Cyclic Nucleotide Phosphodiesterases, Type 2: A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), members of this class have additional specificity for CYCLIC GMP.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.2',3'-Cyclic-Nucleotide Phosphodiesterases: Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.Nucleotides, CyclicPhosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.Cyclic Nucleotide Phosphodiesterases, Type 5: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Cyclic Nucleotide Phosphodiesterases, Type 7: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Rolipram: A phosphodiesterase 4 inhibitor with antidepressant properties.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESPurinonesIsoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Kinetics: The rate dynamics in chemical or physical systems.Cyclic Nucleotide Phosphodiesterases, Type 6: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Phosphodiesterase 3 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 3.Phosphodiesterase 4 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 4.4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.Dibutyryl Cyclic GMP: N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Phosphodiesterase I: A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.Cyclic Nucleotide-Gated Cation Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.Phosphorus-Oxygen Lyases: Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Pyrrolidinones: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)Adenine NucleotidesCyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.Cyclic IMP: Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Phosphodiesterase 5 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 5.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Guanine NucleotidesCattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Xanthines: Purine bases found in body tissues and fluids and in some plants.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Vinca Alkaloids: A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.Cyclic P-OxidesEnzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

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)

*PDE1C

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: ...

*Neuronal 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. doi:10.1371/journal.pone.0010534. PMC 2866544 . PMID 20479890. Pongs O, Lindemeier J, Zhu XR, Theil T, Engelkamp ...

*PDE4A

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication" ( ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ... of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793-812. doi ...

*Cyclic nucleotide

Beavo, Joseph; Sharron Francis; Miles Houslay (2010). Cyclic Nucleotide Phosphodiesterases in Health and Disease. Boca Raton, ... Cyclic nucleotides can be found in many different types of eukaryotic cells, including photo-receptor rods and cones, smooth ... 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 ...

*Discovery 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 5 (PDE5) is widely expressed in several tissues in the body for example brain, lung, kidney, urinary bladder ...

*Pharmacology 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 ...

*TNF inhibitor

Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". J. Allergy Clin. Immunol. 108 (5): 671-80. doi:10.1067/mai. ... Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects". J. Biol. Chem. 281 (20): 14192-206. doi: ... "Binding and Functional Comparisons of Two Types of Tumor Necrosis Factor Antagonists". Journal of Pharmacology and Experimental ... Several 5-HT2A agonist hallucinogens including (R)-DOI, TCB-2, LSD and LA-SS-Az have unexpectedly also been found to act as ...

*PDE4B

This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic ... The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". ... Moustafa F, Feldman SR (May 2014). "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4- ...

*Phosphodiesterase-4 inhibitor

"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor" (pdf). British ... A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action ... Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998). "Rolipram, a type IV-specific phosphodiesterase inhibitor, ... Dinter, H (February 2000). "Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?". BioDrugs. ...

*Phosphodiesterase

Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... Sildenafil (Viagra) is an inhibitor of cGMP-specific phosphodiesterase type 5, which enhances the vasodilatory effects of cGMP ... "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases ...

*PDE9A

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- ...

*PDE8B

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. GRCh38: Ensembl release 89: ...

*Oligodendrocyte

2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase) (Ragheb 1999, p. 14). Pérez-Cerdá, Fernando; Sánchez-Gómez, María ... They are the last cell type to be generated in the CNS. Oligodendroglia, types of glial cells, arise during development from ... Oligodendrocytes (from Greek, meaning cells with a few branches), or oligodendroglia, are a type of neuroglia discovered by Pío ... "Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into ...

*GAF 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 ... The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. Proc. Natl. Acad. Sci. U.S ... Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. EMBO J.. 2000;19(20):5288-99 ...

*CGAS-STING cytosolic DNA sensing pathway

"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 2013 Feb 15;339(6121 ... "Single Nucleotide Polymorphisms of Human STING Can Affect Innate Immune Response to Cyclic Dinucleotides". PLoS ONE October 21 ... 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 ...

*Caffeine-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 ...

*P19 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 endoermal cell types. The cellular ...

*Phosphodiesterase 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. and Weiss, B.: Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" Mol. ... Weiss B (1975). "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv. ...

*PDE1

Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... PDE1 (phosphodiesterase type 1) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase ... Kakkar R, Raju RV, Sharma RK (July 1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)". Cell. Mol. Life ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ...

*Phosphodiesterase 2

"Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell. PDE2 ... June 1997). "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ...

*Pentoxifylline

Essayan DM (2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi ... effect of pentoxifylline as a phosphodiestrase inhibitor was study on the pentylenetetrazol-induced seziure in the wild-type ... Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which ... the effects of non-specific phosphodiesterase inhibition". Clinics. 63 (3): 321-8. doi:10.1590/S1807-59322008000300006. PMC ...

*PDE4D

"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 ...

*Caffeine

Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... Caffeine content in coffee varies widely depending on the type of coffee bean and the method of preparation used; even beans ... Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor. As a competitive nonselective phosphodiesterase ... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity ...

*Cyclic 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) ... Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell. Still, there are some ... such as cyclic adenosine monophosphate, cyclic AMP). Cyclic AMP is synthesized from ATP by adenylate cyclase located on the ...

*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 ... cyclic-nucleotide phosphodiesterase EC 3.1.4.18: now EC 3.1.16.1 EC 3.1.4.19: now EC 3.1.13.3 EC 3.1.4.20: now EC 3.1.13.1 EC ... phosphodiesterase EC 3.1.4.15: adenylyl-(glutamate-ammonia ligase) hydrolase EC 3.1.4.16: 2',3'-cyclic-nucleotide 2'- ...

*Enzyme 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 more toxic to rapidly growing cells than non-dividing cells, since a rapidly growing ... cyclic guanosine monophosphate. This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results from an ...
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 ± ...
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 ...
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 […]. ...
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. ...
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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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 ...
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 ...
Phosphodiesterase-5 (PDE5) inhibitors have been approved by the US Food and Drug Administration for the treatment of erectile dysfunction and more recently for pulmonary arterial hypertension (World Health Organization functional class I). PDE5 inhibitors can induce vasodilation; in addition, through a complex pathway involving nitric oxide, cyclic guanosine monophosphate, and protein kinase G, it can reduce apoptosis and suppress cell proliferation. The presence of PDE5 inhibitors in various tissues and systemic vasculature make them potential targets in a variety of cardiovascular diseases.
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.. ...
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Buy Manforce 100mg Online Tablet relaxes the smooth muscles present in the wall of blood vessels and helps in increasing the flow of blood in certain specific areas of the body. Manforce 100mg Tablet is a phosphodiesterase type 5 inhibitor that helps to relax as well as dilate the blood vessels in the body. It helps to increase the flow of blood in certain parts of the body.
The list of the benefits of using these phosphodiesterase type 5 inhibitors is long and had been well discussed on these forums - other than the obvious
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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 ...
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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 ...
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Author:Indrajeet Sharma, Purshottam K. Kaundal, Malay Sarkar, Tulika Jha, Prakash C. Negi, Ashok K. Sahai, Sanjeev Asotra. Keywords:Cardiopulmonary haemodynamics, Phosphodiesterase-5 inhibitors, Pulmonary hypertension, Tadalafil.. Type:Original Article. Full PDF Abstract ...
Author:Indrajeet Sharma, Purshottam K. Kaundal, Malay Sarkar, Tulika Jha, Prakash C. Negi, Ashok K. Sahai, Sanjeev Asotra. Keywords:Cardiopulmonary haemodynamics, Phosphodiesterase-5 inhibitors, Pulmonary hypertension, Tadalafil.. Type:Original Article. Full PDF Abstract ...
Avanafil prevents phosphodiesterase-5 from destroying cGMP so that cGMP stays around longer. Avanafil was approved by the FDA in April 2012.
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Currently, three phosphodiesterase type 5 (PDE5) inhibitors are available for clinical use in South Africa; sildenafil, vardenafil and tadalafil. The PDE inhibitors are used in males to treat erectile dysfunction. However, sildenafil is also registered for use in the treatment of pulmonary hypertension. Newer studies are investigating the use of these drugs for other conditions, including hypertension, ischaemia or reperfusion injury, myocardial infarction, cardiac hypertrophy, heart failure and other peripheral circulatory conditions, e.g. Raynaud's disease. The article provides a broad overview of the mechanism of action, indications, pharmacokinetics and side-effects of these agents.
Sulfoaildenafil (thioaildenafil) is a synthetic chemical compound that is a structural analog of sildenafil (Viagra). It was first reported in 2005, and it is not approved by any health regulation agency. Like sildenafil, sulfoaildenafil is a phosphodiesterase type 5 inhibitor. Sulfoaildenafil has been found as an adulterant in a variety of supplements which are sold as "natural" or "herbal" sexual enhancement products. A range of designer analogues of USA FDA-approved inhibitors of type-5 cGMP-specific phosphodiesterase (PDE5), such as sildenafil and vardenafil, have been detected in recent years as adulturants in over-the-counter herbal aphrodisiac products and dietary supplements, in an apparent attempt to circumvent both the legal restrictions on sale of erectile dysfunction drugs, which are prescription-only medicines in most Western countries, and the patent protection which prevents sale of these drugs by competitors except under license to their inventors. These compounds have been ...
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It acts by inhibiting cGMP-specific phosphodiesterase type 5 (PDE5), an enzyme that promotes degradation of cGMP, which regulates blood flow in the penis. Sildenafil treats erectile dysfunction by increasing blood flow to the penis during sexual stimulation. This increased blood flow can cause an erection ...
When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis. ...
When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis ...
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ratio-Sildenafil R: Sildenafil belongs to the family of medications known as phosphodiesterase type 5 inhibitors. It is used to treat pulmonary hypertension (high blood pressure in the blood vessels between the heart and lungs) when people have not responded to conventional treatment.
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Clinical evidence in men with erectile dysfunction (ED) shows that the phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate, tadalafil, and vardenafil hydrochloride have favorable safety and efficacy profiles. However, as mild vasodilators, the PDE5 inhibitors are also associated with hemodynamic effects that may be clinically significant, especially when treating men with ED who have comorbid cardiovascular disease. Hemodynamic studies have shown that therapeutic dosages of the PDE5 inhibitors produce only mild and transient changes in mean systolic and diastolic blood pressure and heart rate in healthy men as well as those with ischemic heart disease or chronic stable angina. Overall, PDE5 inhibitors are safe and effective in most patient populations, including men with ischemic cardiovascular disease or those receiving antihypertensive agents, and men with diabetes or those who have undergone nerve-sparing retropubic radical prostatectomy. With the entry of three novel PDE5 ...
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Tadalafil: the evidence for its clinical potential in the treatment of pulmonary arterial hypertension Stuart D. KatzDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USAIntroduction: Pulmonary arterial hypertension (PAH), characterized by increased pulmonary artery pressures in the absence of elevated pulmonary venous pressures, is a progressive disease associated with reduced exercise capacity and increased mortality risk. Current treatments for PAH include nonspecific vasodilators, prostacyclin and related analogs, and endothelin receptor antagonists. Since phosphodiesterase type 5 is highly expressed in pulmonary vascular tissues, agents that selectively inhibit phosphodiesterase type 5 activity induce pulmonary arterial vasodilatation, and are being developed for the treatment of PAH.Aims: The purpose of this review is to evaluate the existing evidence for the use of tadalafil, a selective phosphodiesterase type 5
Cardiac hypertrophy in response to pathologic stress is a major contributor to heart disease. Many studies have revealed that compartmentalized cyclic guanosine monophosphate (cGMP) regulation by phosphodiesterases (PDEs) can potently modify acute and chronic cardiac stress responses. PDE5a normally regulates cGMP generated from nitric oxide (NO)-stimulated soluble guanylate cyclase (sGC) but not natriuretic peptide (NP)-stimulated cGMP. Its inhibition blunts maladaptive hypertrophy and remodeling. Regulators of NP-cGMP remain uncertain. Here we reveal that PDE9a, a highly cGMP-specific PDE (×100 affinity vs PDE5a) that is expressed predominantly in the brain modulates myocyte cGMP as well, targeting NP-stimulated pools. PDE9a gene expression is observed in rat neonatal cardiac myocytes (RNCM) and adult mouse myocytes. Protein expression was identified in myocytes by immunohistochemistry, using gene silencing models as a negative control. PDE9a expression is upregulated by various hypertrophic ...
Evidence is provided for expression and a functional role for phosphodiesterase type V (PDE-V) in the rat isolated small mesenteric artery. The reverse transcription polymerase chain reaction (RT--PCR) demonstrated mRNA for PDE-V, while Western blotting and immunocytochemical studies showed corresponding protein expression. Smooth muscle relaxation to the nitric oxide donor, diethylamine NONOate (DEA NONOate; 1 nM - 10 microM; pEC(50)=6.7+/-0.3) was potentiated significantly by the specific inhibitor of PDE-V, 4-[[3,4-(methylenedioxy)benzyl]amino]-6-chloroquinazoline (MBCQ; 1 microM; pEC(50)=10.5+/-0.04). These data show that PDE-V is expressed in both the smooth muscle and endothelial cells of a resistance artery, and the enzyme can significantly influence nitric oxide-evoked vasorelaxation.
Cyclic nucleotide phosphodiesterase-4 inhibitors: a promising therapeutic approach to premature birth? European Journal of Obstetrics & Gynecology and Reproductive Biology 2004;117(1001):S15-S17.
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Pde1c - Calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase 1C - Mus musculus (Mouse) - Pde1c gene & proteinPde1c - Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C - Mus musculus (Mouse) - Pde1c gene & protein

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ... Type I PDE are activated by the binding of calmodulin in the presence of Ca2+. ... calmodulin-dependent cyclic-nucleotide phosphodiesterase activity Source: MGIInferred from sequence orthologyi*7568196 ... Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators ...
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Hagiwara M, Endo T, Hidaka H Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle . Biochem ... show that Vinpocetine, a phosphodiesterase (PDE) inhibitor known for its minimal side effects and great potential in cognitive ... Solntseva EI, Bukanova JV, Skrebitsky VG The nootropic drug vinpocetine modulates different types of potassium currents in ... Chiu PJ, et al Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and 45Ca-fluxes in the rabbit aorta . ...
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JoVE Search Results: Cyclic Nucleotide Phosphodiesterases%2C Type 5JoVE Search Results: Cyclic Nucleotide Phosphodiesterases%2C Type 5

The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis. Abstract Baillie, George S. University of Glasgow ... Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. Abstract Parent, Carole A. ... Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters. Abstract ... Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation. Abstract ...
more infohttp://labindex.jove.com/group/Cyclic-Nucleotide-Phosphodiesterases%2C-Type-5

Understanding of chest pain in microvascular disease proved by cardiac magnetic resonance image (UMPIRE): study protocol for a...Understanding of chest pain in microvascular disease proved by cardiac magnetic resonance image (UMPIRE): study protocol for a...

Cyclic nucleotide phosphodiesterase type 5 activity limits blood flow to hypoperfused myocardium during exerciseCirculationYear ... The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunctionJ ... Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function ... which is rapidly degraded by cGMP phosphodiesterase (PDE). Recently, phosphodiesterase-5-inhibitor (PDEi) has been reported to ...
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Hao Wang - Research Output
     - Johns Hopkins UniversityHao Wang - Research Output - Johns Hopkins University

Type 5 Cyclic Nucleotide Phosphodiesterases The vigorous immune microenvironment of microsatellite instable colon cancer is ... Phosphodiesterase 5 Inhibitors ... 5, p. 735-740 6 p.. Research output: Contribution to journal › ... Wu, I., Wang, H., Huso, D. & Wahl, R. L., Dec 1 2015, In : EJNMMI Research. 5, 1, 58.. Research output: Contribution to journal ... Jul 5 2015, In : Journal of Translational Medicine. 13, 1, 214.. Research output: Contribution to journal › Article ...
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     - Mayo ClinicBarry A Borlaug, MD - Research Output - Mayo Clinic

Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection ... Van Empel, V. P. M., Kaye, D. M. & Borlaug, B. A., Jul 1 2014, In : American Journal of Cardiology. 114, 1, p. 131-135 5 p.. ... Borlaug, B. A., May 2013, In : Nature Reviews Cardiology. 10, 5, p. 244-246 3 p.. Research output: Contribution to journal › ... Fang, J. C. & Borlaug, B. A., Oct 5 2013, Grossman & Baims Cardiac Catheterization, Angiography, and Intervention: Eighth ...
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Cyclic stretch induces inducible nitric oxide synthase and soluble guanylate cyclase in pulmonary artery smooth muscle cells. ... Brief hyperoxia increases mitochondrial oxidation and increases phosphodiesterase 5 activity in fetal pulmonary artery smooth ... Cyclic stretch stimulates mitochondrial reactive oxygen species and Nox4 signaling in pulmonary artery smooth muscle cells. ... Chi, A. Y., Waypa, G. B., Mungai, P. T. & Schumacker, P. T., Mar 1 2010, In : Antioxidants and Redox Signaling. 12, 5, p. 603- ...
more infohttps://www.scholars.northwestern.edu/en/persons/paul-t-schumacker/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle

Gao, L.<...Gao, L.<...

Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT-mediated TRPC6 expression in pulmonary artery smooth muscle cells ... Single Nucleotide Polymorphism Medicine & Life Sciences Acute Lung Injury Medicine & Life Sciences ...
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Complete nucleotide sequence of full length cDNA for rat α cardiac myosin hea chain. Mcnally, E. M., Gianola, K. M. & Leinwand ... 5 (1052-1060)). Boone, D. L., Turer, E. E., Lee, E. G., Ahmad, R. C., Wheeler, M. T., Tsui, C., Hurley, P., Chien, M., Chai, S ...
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Sildenafil and phosphodiesterase-5 inhibitors for heart failure. Guazzi, M., 2008, In : Current Heart Failure Reports. 5, 2, p ... The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ... Guazzi, M., Reina, G., Tumminello, G. & Guazzi, M. D., Mar 2005, In : European Heart Journal. 26, 5, p. 472-480 9 p.. Research ... Guazzi, M., Reina, G., Tumminello, G. & Guazzi, M. D., Nov 2004, In : Journal of Applied Physiology. 97, 5, p. 1866-1873 8 p.. ...
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... guanosine monophosphate system with type V phosphodiesterase inhibition and exogenous natriuretic peptide: A novel strategy to ... Oral human brain natriuretic peptide activates cyclic guanosine 3′,5′-monophosphate and decreases mean arterial pressure. ... C-type natriuretic peptide: The endothelial component of the natriuretic peptide system. Chen, H. H. & Burnett, J. C. J., 1998 ... B-type natriuretic peptide in organic mitral regurgitation: Determinants and impact on outcome. Detaint, D., Messika-Zeitoun, D ...
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67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis<...67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis<...

We found that phosphodiesterase 5(PDE5), a negative regulator of cGMP, was abnormally expressed in multiple cancers and ... The 67-kDa laminin receptor (67LR) is a laminin-binding protein overexpressed in various types of cancer, including bile duct ... We found that phosphodiesterase 5(PDE5), a negative regulator of cGMP, was abnormally expressed in multiple cancers and ... We found that phosphodiesterase 5(PDE5), a negative regulator of cGMP, was abnormally expressed in multiple cancers and ...
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... the vascular-associated enzyme phosphodiesterase 5 (PDE5), the drug also exerts a lesser but definite inhibitory effect on the ... and type of color vision defects observed at different doses of Viagra. ... the vascular-associated enzyme phosphodiesterase 5 (PDE5), the drug also exerts a lesser but definite inhibitory effect on the ... the vascular-associated enzyme phosphodiesterase 5 (PDE5), the drug also exerts a lesser but definite inhibitory effect on the ...
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Diallyl disulfide potentiates anti-obesity effect of green tea in high-fat/high-sucrose diet-induced obesity<...Diallyl disulfide potentiates anti-obesity effect of green tea in high-fat/high-sucrose diet-induced obesity<...

Cyclic guanosine monophosphate (cGMP) acts as a mediator for the physiological effects of (−)-epigallocatechin-3-O-gallate, the ... Here, we showed that the level of phosphodiesterase 5, a negative regulator of cGMP, was up-regulated in adipose tissues of ... Cyclic guanosine monophosphate (cGMP) acts as a mediator for the physiological effects of (−)-epigallocatechin-3-O-gallate, the ... Cyclic guanosine monophosphate (cGMP) acts as a mediator for the physiological effects of (−)-epigallocatechin-3-O-gallate, the ...
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Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: A phase 2 trial. Robertson, K., Nalepa ... Royal, H., Pierson, R., Fletcher, J., Dillehay, G. & Smith, W., 1996, In : Journal of Nuclear Medicine. 37, 5, p. 878-881 4 p. ... 5 others, Sherman, M. R., Davis, C. J., Miller, L. C., Ingram, D. & Clapp, D., Dec 2012, In : The Lancet Oncology. 13, 12, p. ... 5, p. 455-461 7 p.. Research output: Contribution to journal › Article ...
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Hanson, K. A.<...Hanson, K. A.<...

Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the ... Type 5 Cyclic Nucleotide Phosphodiesterases Medicine & Life Sciences Pulmonary Circulation Medicine & Life Sciences ... Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message. Hanson, K. A., Burns, F., Rybalkin, S. D ... Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity. Hanson, K. A., Ziegler, J. W., Rybalkin, S ...
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A Postmarketing Observational Study to Assess Respiratory Tract Adverse Events in Pulmonary Arterial Hypertension Patients...A Postmarketing Observational Study to Assess Respiratory Tract Adverse Events in Pulmonary Arterial Hypertension Patients...

Drugs Treprostinil (Primary) ; Epoprostenol; Epoprostenol agonists; Treprostinil; Treprostinil; Type 5 cyclic nucleotide ... phosphodiesterase inhibitors * Indications Pulmonary arterial hypertension * Focus Adverse reactions * Acronyms ASPIRE * ...
more infohttp://adisinsight.springer.com/trials/700246064?error=cookies_not_supported&code=442a00c3-25e3-42f2-ac27-70905b0471ce

A Postmarketing Observational Study to Assess Respiratory Tract Adverse Events in Pulmonary Arterial Hypertension Patients...A Postmarketing Observational Study to Assess Respiratory Tract Adverse Events in Pulmonary Arterial Hypertension Patients...

Drugs Treprostinil (Primary) ; Epoprostenol; Epoprostenol agonists; Treprostinil; Treprostinil; Type 5 cyclic nucleotide ... phosphodiesterase inhibitors * Indications Pulmonary arterial hypertension * Focus Adverse reactions * Acronyms ASPIRE * ...
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Search Articles | University of Toronto LibrariesSearch Articles | University of Toronto Libraries

Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4 - chemistry , Cyclic ... Cyclic Nucleotide Phosphodiesterases, Type 4 , Cyclic Nucleotide Phosphodiesterases, Type 3 , Phosphodiesterase Inhibitors - ... Cyclic Nucleotide Phosphodiesterases, Type 4 , Heart Failure - enzymology , Cyclic Nucleotide Phosphodiesterases, Type 3 , ... Cyclic Nucleotide Phosphodiesterases, Type 1 , Cyclic Nucleotide Phosphodiesterases, Type 4 , Eosinophils - drug effects , ...
more infohttps://query.library.utoronto.ca/index.php/search/q?kw=SubjectTerms:Cyclic%20Nucleotide%20Phosphodiesterases,%20Type%201%20-%20antagonists%20&%20inhibitors&page=5

Patente US7660631 - Methods and systems for electrical and/or drug stimulation as a therapy for ... - Google PatentesPatente US7660631 - Methods and systems for electrical and/or drug stimulation as a therapy for ... - Google Patentes

Cyclic nucleotide phosphodiesterases, specifically Type 5, break down cGMP to GMP by catalyzing a reaction that breaks the ... on the Relaxation of Human Corpus Cavernosum Tissue in Vitro and on the Activities of Cyclic Nucleotide Phosphodiesterase ... Carter, et al., "Effect of the Selective Phosphodiesterase Type Inhibitor Sildenafil on Erectile Function in the Anesthetized ... "Sildenafil, a Novel Inhibitor of Phosphodiesterase Type 5 in Human Corpus Cavernosum Smooth Muscle Cells", Life Sciences 62 ( ...
more infohttp://www.google.es/patents/US7660631?dq=flatulence

Yonkenafil « New Drug ApprovalsYonkenafil « New Drug Approvals

... phosphodiesterase type 5 (PDE5) inhibitor Originator Tasly Pharmaceutical Group; Yangtze River Pharmaceutical Group Class ... YonkenafilMw 487.61, MF C₂₄H₃₃N₅O₄S,Cas 804518-63-64H-Pyrrolo[2,3-d]pyrimidin-4-one, 2-[2-ethoxy-5-[(4-ethyl-1-piperazinyl) ... 5 - methyl - 7 - n-Propyl-3 7 - PYRROLINE [2, 3 - d] pyrimidin - 4 - onePhase2 Erectile dysfunction扬子江药业 (Originator), 天士力制药 ( ... sulfonyl]phenyl]-3,7-dihydro-5-methyl-7-propyl-,2- [2-ethoxy --5- (4 - ethylpiperazine -1-- sulfonyl) phenyl] - ...
more infohttps://newdrugapprovals.org/2016/06/29/yonkenafil/?share=google-plus-1

Phosphodiesterase type 1, calcitonin gene-related peptide and vasoactive intestinal polypeptide are involved in the control of...Phosphodiesterase type 1, calcitonin gene-related peptide and vasoactive intestinal polypeptide are involved in the control of...

... whereas only little is known on the role of other key proteins and mediators of cyclic nucleotide mediated signaling in this ... the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in ... the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in ... the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in ...
more infohttps://moh-it.pure.elsevier.com/en/publications/phosphodiesterase-type-1-calcitonin-gene-related-peptide-and-vaso

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients with HFpEF ...Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients with HFpEF ...

Cyclic Nucleotide Phosphodiesterases, Type 5, Diabetes Mellitus, Dipeptidyl-Peptidase IV Inhibitors, Dipeptidyl-Peptidases and ... Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection ... In reference to I-PRESERVE and RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in ... 3 Phosphodiesterase-5 inhibition was thought to have potential in targeting the multiple pathophysiological disorders that ...
more infohttps://www.acc.org/latest-in-cardiology/articles/2017/04/13/12/19/clinical-and-echocardiographic-characteristics-and-cardiovascular-outcomes?w_nav=CI

Engineered Biosynthesis of 5/5/6 Type Polycyclic Tetramate Macrolactams in an Ikarugamycin (5/6/5 Type)-Producing Chassis.Engineered Biosynthesis of 5/5/6 Type Polycyclic Tetramate Macrolactams in an Ikarugamycin (5/6/5 Type)-Producing Chassis.

Combinatorial biosynthesis of 5/5/6 type polycyclic tetramate macrolactams (PoTeMs) was achieved in an engineered ikarugamycin ... Cyclic Nucleotide Phosphodiesterases, Type 1. A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily ... type II (intermediate form), and type III (Kugelberg-Welander disease). Type I is fatal in infancy, type II has a late ... The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In ...
more infohttps://www.bioportfolio.com/resources/pmarticle/2617609/Engineered-Biosynthesis-of-5-5-6-Type-Polycyclic-Tetramate-Macrolactams-in-an.html

cGMP signal termination  - StrathprintscGMP signal termination - Strathprints

... cyclic GMP, cyclic nucleotide phosphodiesterases, type 1, cyclic nucleotide phosphodiesterases, type 5, enzyme activation, GTP- ... cyclic-AMP phosphodiesterases, 3,5-cyclic-GMP phosphodiesterases, animals, ...
more infohttps://strathprints.strath.ac.uk/34930/
  • The aim of the present study was to evaluate in the human vagina, by means of immunohistochemistry, the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in relation to calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and protein gene product 9.5 (PGP 9.5). (elsevier.com)
  • Yonkenafil hydrochloride, useful for treating erectile dysfunction and other PDE-5 mediated diseases eg female sexual dysfunction, benign prostatic hyperplasia, hypertension, allergic asthma, bronchitis, glaucoma, gastrointestinal motility disorders or Alzheimer's Ydisease. (newdrugapprovals.org)
  • This includes a few exogenous, vertically transmitted and endogenous viruses of mice (type B) and some primate and sheep viruses (type D). MAMMARY TUMOR VIRUS, MOUSE is the type species. (bioportfolio.com)
  • Conclusion: Key mediators of the cyclic AMP and cyclic GMP pathways are co-localized in nerves seen in close proximity to vascular smooth muscle expressing PDE1. (elsevier.com)
  • In a telephone survey of 5990 Australian men aged forty years or older,5 only 30% of males with reasonable-to-extreme erectile dysfunction discussed their problem with a health professional. (sdmnapoli.it)
  • Implant-type tissue-engineered cartilage derived from human auricular chondrocyte may maintain cartilaginous property even under osteoinductive condition. (bioportfolio.com)
  • Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. (drugbank.ca)
  • Examples are supplied to illustrate each of these major points: Our presentation will include data gleaned from clinical trials plus postmarketing information on the incidence, duration, and type of color vision defects observed at different doses of Viagra. (elsevier.com)
  • Part III knowledge report that doses of 20 mg PO improved sexual operate in 64% of diabetics with ED. In one medical research, positive responses had been famous at doses of 2, 5, 10, and 25 mg. (sdmnapoli.it)
  • Doses 5 mg or more had been superior to placebo in inducing and sustaining erections adequate for penetration. (sdmnapoli.it)
  • 6. The method of claim 5 wherein the stimulation pulses are infusion pulses providing at least one of an inhibitory drug, GABA, phentolamine, and a norepinephrine antagonist. (google.es)
  • 4,5 Although tested drug therapy did not show benefit, this particular study suggested that HFpEF is not one entity but rather a disease spectrum. (acc.org)