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

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. (1/192)

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)

cGMP binding to noncatalytic sites on mammalian rod photoreceptor phosphodiesterase is regulated by binding of its gamma and delta subunits. (2/192)

The binding of cGMP to the noncatalytic sites on two isoforms of the phosphodiesterase (PDE) from mammalian rod outer segments has been characterized to evaluate their role in regulating PDE during phototransduction. Nonactivated, membrane-associated PDE (PDE-M, alpha beta gamma2) has one exchangeable site for cGMP binding; endogenous cGMP remains nonexchangeable at the second site. Non-activated, soluble PDE (PDE-S, alpha beta gamma2 delta) can release and bind cGMP at both noncatalytic sites; the delta subunit is likely responsible for this difference in cGMP exchange rates. Removal of the delta and/or gamma subunits yields a catalytic alphabeta dimer with identical catalytic and binding properties for both PDE-M and PDE-S as follows: high affinity cGMP binding is abolished at one site (KD >1 microM); cGMP binding affinity at the second site (KD approximately 60 nM) is reduced 3-4-fold compared with the nonactivated enzyme; the kinetics of cGMP exchange to activated PDE-M and PDE-S are accelerated to similar extents. The properties of nonactivated PDE can be restored upon addition of gamma subunit. Occupancy of the noncatalytic sites by cGMP may modulate the interaction of the gamma subunit with the alphabeta dimer and thereby regulate cytoplasmic cGMP concentration and the lifetime of activated PDE during visual transduction in photoreceptor cells.  (+info)

cGMP phosphodiesterase-alpha mutation causes progressive retinal atrophy in the Cardigan Welsh corgi dog. (3/192)

PURPOSE: To screen the alpha-subunit of cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE6A) as a potential candidate gene for progressive retinal atrophy (PRA) in the Cardigan Welsh corgi dog. METHODS: Single-strand conformation polymorphism (SSCP) analysis was used to screen short introns of the canine PDE6A gene for informative polymorphisms in members of an extended pedigree of PRA-affected Cardigan Welsh corgis. After initial demonstration of linkage of a polymorphism in the PDE6A gene with the disease locus, the complete coding region of the PDE6A gene of a PRA-affected Cardigan Welsh corgi was cloned in overlapping fragments and sequenced. SSCP-based and direct DNA sequencing tests were developed to detect the presence of a PDE6A gene mutation that segregated with disease status in the extended pedigree of PRA-affected Cardigan Welsh corgis. Genomic DNA sequencing was developed as a diagnostic test to establish the genotype of Cardigan Welsh corgis in the pet population. RESULTS: A polymorphism within intron 18 of the canine PDE6A gene was invariably present in the homozygous state in PRA-affected Cardigan Welsh corgis. The entire PDE6A gene was cloned from one PRA-affected dog and the gene structure and intron sizes established and compared with those of an unaffected animal. Intron sizes were identical in affected and normal dogs. Sequencing of exons and splice junctions in the affected animal revealed a 1-bp deletion in codon 616. Analysis of PRA-affected anti obligate carrier Cardigan Welsh corgis showed that this mutation cosegregated with disease status. CONCLUSIONS: A single base deletion at codon 616 in the PDE6A gene cosegregated with PRA status with zero discordance in Cardigan Welsh corgis with PRA. A lod score of 4.816 with a recombination fraction (theta) of zero strongly suggests that this mutation is responsible for PRA in the breed. The mutation is predicted to lead to a frame shift resulting in a string of 28 altered codons followed by a premature stop codon. The authors suggest that this type of PRA be given the name rod-cone dysplasia 3 (rcd3).  (+info)

Screening of the gene encoding the alpha'-subunit of cone cGMP-PDE in patients with retinal degenerations. (4/192)

PURPOSE: To screen the exons of the gene encoding the alpha'-subunit of cone cyclic guanosine monophosphate (cGMP>phosphodiesterase (PDE6C) for mutations in a group of 456 unrelated patients with various forms of inherited retinal disease, including cone dystrophy, cone-rod dystrophy, macular dystrophy, and simplex/multiplex and autosomal recessive retinitis pigmentosa. METHODS: The 22 exons of the PDE6C gene were screened for mutations either by denaturing gradient gel electrophoresis and single-strand conformation polymorphism electrophoresis (SSCP) or by SSCP alone; variants were sequenced directly. RESULTS: Although many sequence variants were found, none could be associated with disease. CONCLUSIONS: The results show that PDE6C was not the site of the amutations responsible for the types of inherited retinal degenerations analyzed in the large population of patients 'in the present study. The types of degeneration included those that predominantly affect cone-mediated function (cone and cone-rod dystrophies) or rod-mediated function (retinitis pigmentosa) or that have a predilection for disease in the macula (macular dystrophies).  (+info)

Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa. (5/192)

PURPOSE: To determine the mutation spectrum of the PDE6A gene encoding the alpha subunit of rod cyclic guanosine monophosphate (cGMP)phosphodiesterase and the proportion of patients with recessive retinitis pigmentosa (RP) due to mutations in this gene. METHODS: The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen all 22 exons of this gene for mutations in 164 unrelated patients with recessive or isolate RP. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS: Four new families were identified with five novel mutations in this gene that cosegregated with disease. Combining the data presented here with those published earlier by the authors, eight different mutations in six families have been discovered to be pathogenic. Two of the mutations are nonsense, five are missense, and one affects a canonical splice-donor site. CONCLUSIONS: The PDE6A gene appears to account for roughly 3% to 4% of families with recessive RP in North America. A compilation of the pathogenic mutations in PDE6A and those reported in the homologous gene PDE6B encoding the beta subunit of rod cGMP-phosphodiesterase shows that the cGMP-binding and catalytic domains are frequently affected.  (+info)

Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. (6/192)

Retinitis pigmentosa (RP) is the most common inherited retinal disease, in which photoreceptor cells degenerate, leading to blindness. Mutations in the rod photoreceptor cGMP phosphodiesterase beta subunit (PDEbeta) gene are found in patients with autosomal recessive RP as well as in the rd mouse. We have recently shown that lentivirus vectors based on human immunodeficiency virus (HIV) type 1 achieve stable and efficient gene transfer into retinal cells. In this study, we evaluated the potential of HIV vector-mediated gene therapy for RP in the rd mouse. HIV vectors containing a gene encoding a hemagglutinin (HA)-tagged PDEbeta were injected into the subretinal spaces of newborn rd mouse eyes. One to three rows of photoreceptor nuclei were observed in the eyes for at least 24 weeks postinjection, whereas no photoreceptor cells remained in the eyes of control animals at 6 weeks postinjection. Expression of HA-tagged PDEbeta in the rescued photoreceptor cells was confirmed by two-color confocal immunofluorescence analysis using anti-HA and anti-opsin antibodies. HIV vector-mediated gene therapy appears to be a promising means for the treatment of recessive forms of inherited retinal degeneration.  (+info)

The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta, interacts with the Arf-like protein Arl3 in a GTP specific manner. (7/192)

Recently, we have shown that the delta subunit of the cGMP phosphodiesterase (PDE delta) interacts with the retinitis pigmentosa guanine regulator (RPGR). Here, using the two-hybrid system, we identify a member of the Arf-like protein family of Ras-related GTP-binding proteins, Arl3, that interacts with PDE delta. The interaction was verified by fluorescence spectroscopy and co-immunoprecipitation. Arl3 features an unusually low affinity for guanine nucleotides, with a KD of 24 nM for GDP and 48 microM for GTP. Fluorescence spectroscopy shows that PDE delta binds and specifically stabilizes the GTP-bound form of Arl3 by strongly decreasing the dissociation rate of GTP. Thus, PDE delta is an effector of Arl3 and could provide a novel nucleotide exchange mechanism by which PDE delta stabilizes Arl3 in its active GTP-bound form.  (+info)

A point mutation (W70A) in the rod PDE-gamma gene desensitizing and delaying murine rod photoreceptors. (8/192)

PURPOSE: To examine the corneal electroretinogram (ERG) of transgenic mice (W70A mice) carrying a point mutation (W70A) in the gene encoding for the gamma-subunit of rod cGMP phosphodiesterase (PDEgamma). METHODS: The ERG of W70A mice was compared with that of normal mice. Cone responses were separated from rod responses by light adaptation, whereas rod sensitivity was assessed by threshold stimulation with dim light. Spectral sensitivity curves of the ERG were obtained using a constant response criterion. RESULTS: The ERG of the W70A mouse has a desensitized, delayed rod b-wave at threshold, and a prolonged rod b-wave at higher flash intensities. The a-wave is absent even at maximal stimulation. The cone ERG of the W70A mouse is indistinguishable from that of normal mice. The spectral sensitivity of the W70A mouse is maximal in the UV spectrum, in contrast to the normal mouse, which is most sensitive in the green region of the spectrum. This supports the interpretation of the results as normal cone and abnormal rod function in the W70A mouse. CONCLUSIONS: The W70A mouse represents new model of stationary nyctalopia that can be recognized by its unusual ERG features.  (+info)

Agility Training: Cardigan Welsh Corgis can be taught to accomplish obstacle courses, relays, and agility courses. With dedication, clear instructions and proper incentives, Cardigan Welsh Corgis have been known to rank well in agility competitions. Though they are not as speedy as other dog breeds, the Cardigan general stability, physical stamina and strength enable them to engage in intense competition.. Agility training must be completed with an experienced dog trainer, who will know the pace at which training should progress. Corgis should hold off on jumping and heavy contact sections until they are older than 18-24 months. Their spinal structures need ample time to develop, so be sure to protect young dogs from over-training. A dogs growth plates typically close when they are between 9-14 months old, meaning that training should not commence until the dogs dwarfish anatomy can sustain it. Likewise, monitoring diet is an important aspect of skill training, since Corgis have a tendency to ...
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We thank Prof. Dr. Wolfgang Baehr (University of Utah, USA) for providing us PrBP/δ expression vector. We are obliged to Ms. Ingrid Semjonow, Ms. Helena Seibel and Mr. Brian Bauer for their excellent technical assistance in purifying reagents and in protein preparations. We are grateful to Uwe Müller, Manfred Weiss and the scientific staff of the BESSY-MX/Helmholtz Zentrum Berlin für Materialien und Energie at beamlines BL14.1, BL14.2 and BL14.3 operated by the Joint Berlin MX-Laboratory at the BESSY II electron storage ring (Berlin-Adlershof, Germany) and the scientific staff of the European Synchrotron Radiation Facility (ESRF, Grenoble) at beamlines ID14-1, ID14-4, ID23-1, ID23-2, ID30A, ID30B and ID29, where the data were collected, for continuous support. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB740 to T.M., C.M.T.S, M.H., P.S.; SFB1078-B6 to P.S.; SFB958 to C.M.T.S.), DFG Cluster of Excellence Unifying Concepts in Catalysis (Research Field D/E to ...
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Section 4. Elections. The election of Officers, Delegate to the American Kennel Club and Directors shall be conducted by secret mail ballot, or sent in accordance with the AKCs most current procedure on Electronic Balloting for AKC Parent Clubs*** Such decisions shall be passed by a majority vote of those regular members casting ballots. Ballots to be valid must be received by the Recording Secretary on or before March 15th of the year of the election of the new Board. The Board shall appoint three election tellers who are regular members in good standing and who are neither members of the current Board nor candidates on the ballot to count the ballots and report the results to the Recording Secretary.. The nominated candidate receiving the largest number of votes for each position shall be declared elected, and all candidates shall be so notified in writing by the Recording Secretary by April 1st. If any duly elected candidate withdraws his name or is unable to serve for any reason, the ...
Section 4. Elections. The election of Officers, Delegate to the American Kennel Club and Directors shall be conducted by secret mail ballot, or sent in accordance with the AKCs most current procedure on Electronic Balloting for AKC Parent Clubs*** Such decisions shall be passed by a majority vote of those regular members casting ballots. Ballots to be valid must be received by the Recording Secretary on or before March 15th of the year of the election of the new Board. The Board shall appoint three election tellers who are regular members in good standing and who are neither members of the current Board nor candidates on the ballot to count the ballots and report the results to the Recording Secretary.. The nominated candidate receiving the largest number of votes for each position shall be declared elected, and all candidates shall be so notified in writing by the Recording Secretary by April 1st. If any duly elected candidate withdraws his name or is unable to serve for any reason, the ...
warm enough premature baby Autumn 2013 cardigans for premature babies when baby is allowed layers in the special care by unit you may like to pick out a tiny bay cardigan to keep them warm enough and cosy.new lines have just arrived for premature babies ,loads of snug fitting fancy cardigans see them here for both boys and girls Cheeky …Continue reading →. ...
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Slouchy ribbed fabric creates a cardigan that has an open front and slip pockets for casual layering appeal. Knit fabric Open front Front slip pockets Long sleeves Ribbed CONTENT + CARE Rayon/polyester Wash cold; dry flat Imported plus size cardigan SIZE + FIT Model is 511, size 1 Size 2 measures 34 from shoulder
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All([ afterallSerifR (), afterallSerifM (), proximaNovaR (), proximaNovaS (), proximaNovaRegularI (), ]), Sheer open front cardigan loft - AfterallSerifM (); Pocket open cardigan
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This hairy alpaca cardigan is perfect for becoming a proper ice queen, with a touch of irony. It is a cardigan with pom-poms and a hood, open in the front with a zipper. A truly versatile garment dedicated to anyone who faces life with a smile.
Onto something a tad more cheerful than the state of my under-insulated office: a new cardigan! I have been on the hunt for the perfect cardigan for months! I found one that almost fit the bill at Forever 21 a couple of months ago but just wasnt blown away by it; I found several cute ones at New York & Co. and Old Navy (and did buy 1 that I adore), but they still werent matching the vision inside my head; and while Id continually checked Target (it is my mecca afterall, so Im there more often than I care to admit) even this love of my life couldnt deliver. In fact, I was seriously disappointed with Targets cardigan and sweater selection this year. I mean, come on Target, cardigans are all the rage right now, plus the world is full of nerdy all-the-time-cardigan-lovers like me and all you have are thin worthless ones or basic cardis?! Unacceptable. Well, after last night, Target and I are back on good terms again because I found exactly what Id been looking for (and for only $20) ...
Cambia is a light and feminine cardigan that works as an extra layer to wear at work, but its pretty enough to go out to dinner that evening. The front edgings cleverly form a sash that ties in the front and each edging is flanked by a pretty openwork cable. The cable is repeated on the sleeves for a charming accent, and also appears on the back. The rest of the body is in stockinette stitch. The sweater is knitted in one piece from the bottom up, the visual effect of the vertical cables will be slimming to many figures while the gentle waist shaping creates a flattering fit.
The fabric: a snuggly burgundy knit thats a stretchy fit with a lightweight feel. The fit: a draped front that flatters, with a slightly longer hem. But wait, theres more; the black stripes lend a minimalist touch that catches the eye without overwhelming the look.|div||br||/div||div||b|Model is 5’10”, size 1|br||/b||div||ul||li style=LIST-STYLE-POSITION: outside !important; LIST-STYLE-TYPE: disc !important|Size 1 measures 47 from shoulder|/li||li style=LIST-STYLE-POSITION: outside !important; LIST-STYLE-TYPE: disc !important|Acrylic/wool|/li||li style=LIST-STYLE-POSITION: outside !important; LIST-STYLE-TYPE: disc !important|Wash cold, dry flat|/li||li style=LIST-STYLE-POSITION: outside !important; LIST-STYLE-TYPE: disc !important|Imported plus size cardigan|/li||/ul||/div||/div|
Lush hibiscus blossoms in dark olive on navy pattern this jacquard-knit cardigan of softest pima. The knit stitch drapes beautifully and looks stunning belted with its removable sash. Styled with a ribbed shawl collar and buttonless placket.
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Keep loved ones warm with our one-of-a-kind picture knit Cardigan. This item is a true keepsake.. As the sun rises, many creatures of the jungle come out to play! Can you find them?. Soft breathable Cotton / nylon. Machine washable. Garment hold its shape so you can enjoy it over and over again.. ...
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Super sweet, this cardigan shows lots of attention to detail. It measures 38 inches bust and 23 inches back length. Three-quarter length sleeves. Medium.
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Long cardigan | Thick, knitted quality | Regular fit | Long sleeved | Open with no closure | Front pockets | Ribbed at all edges | Length: 70 cm in a size S | The model is 180 cm tall and is wearing a size S
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Purpose: : Leber congenital amaurosis (LCA) is a common cause of infantile blindness. Here we study one LCA subtype caused by a mutation in the gene encoding the aryl hydrocarbon receptor-interacting protein like 1 (AIPL1). AIPL1 is an FK506-binding homolog specifically expressed in photoreceptor cells. Previous studies suggest that AIPL1 serves as a specialized chaperone for the synthesis of rod cGMP phosphodiesterase (PDE6) in photoreceptor cells. However, it is not yet clear whether AIPL1 primarily serves as a quantity control or a quality control. To address this question, we co-express AIPL1 and subunits of PDE6 followed by biochemical characterization. Methods: : To introduce AIPL1 into HEK293 cells, an AIPL1 HEK 293 stable cell line was established. Plasmids expressing PDE6 subunits were then transduced into HEK293 cells and the AIPL1 HEK293 stable cell line, respectively. Immunoblotting was used to determine the expression levels for PDE6 subunits. SDS-PAGE followed by immunoblotting was ...
What is the difference between a Pembroke and a Cardigan Welsh Corgi?. Until 1934, the Kennel Club (Great Britain) classed the Pembroke and Cardigan Welsh Corgis as two varieties of one breed. Most fanciers believe that the two breeds evolved separately, the Pembroke from the Spitz family and the Cardigan from the Dachshund family.. The theory is plausible, with anatomical evidence to support it, but impossible to verify or disprove. Interbreeding between the two breeds occurred but was not widespread. With the recognition of the breeds as totally separate by the Kennel Club, breeders gave up interbreeding and the individual integrity of both breeds were saved.. The differences between Pems and Cardis are as notable as are the similarities:. Similarities: Erect ears; foxy head; long, low body; intelligent; energetic; ability to herd and act as a guard dog. Differences: The Pembroke is an extroversive breed, the Cardi is friendly but may be reserved with strangers. The Pembrokes ears are erect, ...
The rod photoreceptor cGMP-gated cation channel, consisting of three α- and one β subunit, controls ion flow into the rod outer segment (ROS). In addition to the β-subunit, the Cngb1 locus encodes an abundant soluble protein, GARP2 that binds stoichiometrically to rod photoreceptor cGMP phosphodiesterase type 6 (PDE6). To examine the in vivo functional role of GARP2 we generated opsin promoter-driven transgenic mice overexpressing GARP2 three-fold specifically in rod photoreceptors. In the GARP2 overexpressing transgenic mice (tg), the endogenous channel β-subunit, cGMP phosphodiesterase α-subunit, peripherin2/RDS and guanylate cyclase I were present at WT levels and were properly localized within the ROS. While localized properly within ROS, two proteins cGMP phosphodiesterase α-subunit (1.4-fold) and cGMP-gated cation channel α-subunit (1.2-fold) were moderately, but significantly elevated. Normal stratification of all retinal layers was observed, and ROS were stable in numbers but were 19%
Classic Elite Firefly Azul Hooded Cardigan Kit - Crochet for Adults Kits - Taken from Classic Elite Surfs Up: A cardigan with hood and tie closure with flowing lacy trim at hem and cuffs. This pattern is from Classic Elite Surfs Up, pg 10 - Azul Size US F/5 crochet hook (or size needed to obtain gauge) required but not included. Finished Bust Measurements: 33 (36, 39, 46, 49, 52) after blocking. Gauge: 20 sts and 9 rows over 4 Color Shown is 7757 Chicory. Classic Elite Firefly Azul Hooded Cardigan Kit - Crochet for Adults Kits are available now at Jimmy Beans Wool with Free U.S. Flat Rate shipping for orders over $75, $4 U.S. Flat Rate shipping on all other orders!
Im a breeder and exhibitor of Cardigan Welsh Corgis under the Cheysuli kennel prefix. I started with Labs many years ago in obedience, then got talked into *A* Cardigan by a breeder-friend. Heh. One was not enough! I also teach conformation handling classes. My real job is being a fulltime fantasy author. I have three series published: The Chronicles of the Cheysuli (where my kennel name came from); the Sword-Dancer saga; the first two books in the 4-volume Karavans series, plus a few historical novels ...
Im a breeder and exhibitor of Cardigan Welsh Corgis under the Cheysuli kennel prefix. I started with Labs many years ago in obedience, then got talked into *A* Cardigan by a breeder-friend. Heh. One was not enough! I also teach conformation handling classes. My real job is being a fulltime fantasy author. I have three series published: The Chronicles of the Cheysuli (where my kennel name came from); the Sword-Dancer saga; the first two books in the 4-volume Karavans series, plus a few historical novels ...
Cardigan Bay is home to the only resident population Bottle-nosed Dolphins in English and Welsh waters. They are regular visitors to this part of the coast, especially during calm weather, although their visits are impossible to predict. They provide an unforgettable sight as they leap high out of the water ...
A beautifully-made, expertly-finished baby and child cardigan in 100% fine organic Merino wool, with pearl buttons. A sober yet beautiful and timeless design. Buy now while stock lasts.
A beautifully-made, expertly-finished baby and child cardigan in 100% fine organic Merino wool, with pearl buttons. A sober yet beautiful and timeless design. Buy now while stock lasts.
Part of our 旅 TABI collection, a collaboration between icebreaker and Japanese apparel house GOLDWIN, the cool-lite™ Cardigan combines the natural performance benefits of merino wool with a refined aesthetic thats perfect for everyday urban style. The cool-lite™ Cardigan combines a classic button-down silhouette with our cool-lite™ fabric-a sustainable blend of soft merino wool, natural TENCEL™ and nylon, with a touch of LYCRA® for stretchy comfort. This jersey tops lightweight, breathable feel make it an ideal cool-weather layering piece with incredible next-to-skin softness, and its rib-knit cuffs and hem make for classic finishing details.
It is historically unclear whether the CWC was used primarily for moving cattle and sheep only for short distances, or whether the CWC was occasionally used to move herds of cattle or flocks of sheep longer distances into the flatter pasturelands and markets of England. In either case, the CWC had to be a sound working animal capable of sudden energy bursts and longer, more energy efficient movement.-- All of this while still in a small, dwarfed body! This generalised approach to the job of a farm dog does not allow for a specialised structure (e.g. greyhound for speed at the gallop, or a German Shepherd Dog for fast moving trot.) Instead the Cardigan Welsh Corgi structure requires a very careful balancing act between its three primary functions ...
In simple terms, genes are like recipes for making proteins. All the cells in our bodies read genetic information so they can make the critical proteins necessary to stay healthy and function properly. If there is a mistake in a gene - that is, a misspelling - a protein might not be made correctly and cells in the retina might degenerate and cause vision loss.. These misspellings are called mutations, and just like a mistake in a recipe, some mutations are more devastating than others. For example, when baking a cake, lets say there is an error in the recipe. It incorrectly calls for a quarter cup of sugar, when the right amount is a half of a cup. The cake may not taste great, but it is still edible. But lets say the instruction for adding flour is omitted entirely. Then the cake will be a complete failure and go uneaten.. Well, the same concept applies to genetic mutations in inherited retinal diseases. Some mutations can lead to devastating vision loss while others cause less severe, ...
The gene therapy technology already exists to treat most inherited retinal disease. The current challenge is to drive down the costs of implementing the technology.
Professor Anthony Moore, wrote an interesting article on gene testing for inherited retinal disease (IRD) in Ophthalmology, a scientific journal for eyes.
I fell in love with Cardigan Corgis in 2004. Since then I learned LOTS on dog breeding, showing and exhibiting. I enjoy having fun with the pack - that includes dog shows and trials. I go to comic cons with my service dog and lots of concerts. If you are not having fun, might as well be dead - Hemmingway ...
I fell in love with Cardigan Corgis in 2004. Since then I learned LOTS on dog breeding, showing and exhibiting. I enjoy having fun with the pack - that includes dog shows and trials. I go to comic cons with my service dog and lots of concerts. If you are not having fun, might as well be dead - Hemmingway ...
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LOCH-Class Anti-Submarine Frigate ordered from Henry Robb of Leith in 1943 and was to be named LOCH LAXFORD. However after a policy change to meet the need for anti-aircraft, escorts for service in the Far East, the contract was changed. She was completed to a revised design as a BAY-Class Anti-aircraft frigate and laid down on 14th April 1944 as Job No J11861 (Yard Number 348). Launched on 28th December 1944 as HMS CARDIGAN BAY and the first RN ship to carry the name. Her build was completed on 15th June 1945. (See General Information for details of design changes to the basic LOCH Class hull structure).. G e o g r a p h i c D a t a. Grid Reference:SN4080.. Bay on west coast of Wales and an extension of St. George s Channel.. (Note: Coastline of 130 miles includes Guided Weapons firing range off. Aberporth at southern end.). B a t t l e H o n o u r s. KOREA 1950 53. H e r a l d i c D a t a. Badge: On a Field, Barry wavy of 10 White and Blue,. a demi-dragon erased rampant red, armed and. with ...
Choose your shade-this reversible cardigan offers you two beautiful options. Long and luxe, its finished with long sleeves and a hood to keep you comfy on all your weekend adventures. Soft, cotton-blend fabric. Reversible black to graphite gray design with long sleeves, button closure, and hood detail. Regular length: 33.5. Petite length: 31.5. Cotton, nylon. Machine wash. Imported.
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curly red haired girl undresses her white panties and cardigan while eating an apple in the bed 740176: -Plato, Epigram VII Atalanta, also of Greek mythology, raced all her suitors in an attempt to avoid marriage. She outran all but Hippomenes (a.k.a. Melanion, a name possibly derived from melon the Greek word for both apple and fruit in general), who defeated her by cunning, not speed. Hippomenes knew that he could not win in a fair race, so he used three golden apples (gifts of Aphrodite, the goddess of love) to distract Atalanta. It took all three apples and all of his speed, but Hipp…
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We love longer cardigans for layering (and draping over office chairs...). This one comes in a slew of collect-them-all colors too. Oversized fit. Sits low on hip. Merino wool. Long sleeves. Rib trim at neck, cuffs and hem. Dry clean. Import. Online only.
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If you own, or are thinking about owning, a Welsh corgi, you need to know these corgi dog-care facts. Plus, get tips on Welsh corgi care and grooming. Were also sharing our cutest corgi-inspired gifts.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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 ... 9 (6): 299-301. doi:10.1124/mi.9.6.5. PMC 2861806. PMID 20048135. Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, ...
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. ...
"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 ...
It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine ... "The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I ... Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5'-pApA (phosphadenylyl adenosine). pApA is also ... "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9 ...
White matter Schwann cells 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase) List of human cell types derived from the germ ... Oligodendrocytes are a type of glial cell. They arise during development from oligodendrocyte precursor cells (OPCs), which can ... They are the last cell type to be generated in the CNS. Oligodendrocytes were discovered by Pío del Río Hortega. ... Oligodendrocytes (from Greek 'cells with a few branches'), or oligodendroglia, are a type of neuroglia whose main functions are ...
This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the ... taste+receptors,+type+1 at the US National Library of Medicine Medical Subject Headings (MeSH) taste+receptors,+type+2 at the ... The HCN channels were such a proposal; as they are cyclic nucleotide-gated channels. The two ion channels now suggested to ... Type 1, sweet, first characterized in 2001: TAS1R2 - TAS1R3 Type 2, bitter, first characterized in 2000: In humans there are 25 ...
"Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell. PDE2 ... "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... June 1997). "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes ...
Johner, A., Kunz, S., Linder, M., Shakur, Y. and Seebeck, T. (2006). "Cyclic nucleotide specific phosphodiesterases of ... http://www.garlandscience.com/textbooks/0815323042.asp?type=reviews. *Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ...
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 which 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 ...
Sun L, Wu J, Du F, Chen X, Chen ZJ (February 2013). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type ... cGAMP was found to be much more potent than other cyclic di-nucleotides (c-di-GMP and c-di-AMP). cGAMP was shown to ... phosphodiesterases. Other advantages of the unique 2'-5' linkage may be that cGAMP is able to bind multiple allelic variants of ... Cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide (CDN) and the first to be found in metazoans. Other CDNs (c-di-GMP and c-di-AMP ...
Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. CiteSeerX 10.1.1.319. ... Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell. cAMP-dependent pathway is ... Molecules that inhibit the cAMP pathway include: cAMP phosphodiesterase converts cAMP into AMP by breaking the phosphodiester ... Increases in concentration of the second messenger cAMP may lead to the activation of cyclic nucleotide-gated ion channels ...
Cyclic-nucleotide 3'-phosphodiesterase and multiple molecules of the Immune system. GRCh38: Ensembl release 89: ENSG00000197971 ... In general, the major form of MBP is a protein of about 18.5 Kd (170 residues). In melanocytic cell types, MBP gene expression ... 21 (6): 665-76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. "Entrez Gene: myelin basic protein". Berger T, Rubner P, ... 6 (1): 16-22. doi:10.1016/0888-7543(90)90443-X. PMID 1689270. Kishimoto A, Nishiyama K, Nakanishi H, et al. (1985). "Studies on ...
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 ...
... cGMP in turn activates cyclic nucleotide-dependent protein kinase G, which phosphorylates various proteins that play a role in ... Here is a list of examples of the nitrate type (in alphabetical order): Acesaniamide[citation needed] Diethylene glycol ... PDE5 inhibitors block deactivation of cGMP by the enzyme phosphodiesterase-5. In combination with the increased cGMP production ... Guanylate cyclase produces cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). ...
... cyclic-nucleotide 2'-phosphodiesterase EC 3.1.4.17: 3',5'-cyclic-nucleotide phosphodiesterase EC 3.1.4.18: now EC 3.1.16.1 EC ... type I site-specific deoxyribonuclease EC 3.1.21.4: type II site-specific deoxyribonuclease EC 3.1.21.5: type III site-specific ... 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 ... cyclic-guanylate-specific phosphodiesterase EC 3.1.4.53: 3',5'-cyclic-AMP phosphodiesterase EC 3.1.4.54: N- ...
However, a receptor-type GC in mammalian sperm has yet to be identified. Mouse sperm express other channels such as CatSper1. ... Mutations causing RP have also been found in the rhodopsin gene and in the alpha- and beta-subunits of rod phosphodiesterase, ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ... alpha 2 Cyclic nucleotide-gated channel alpha 3 Cyclic nucleotide-gated channel alpha 4 Cyclic nucleotide gated channel beta- ...
"Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell.[9]. ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488-520. doi:10.1124/pr. ...
... s are a type of phosphodiesterase inhibitors. Inhibition of the PDE isoenzyme 3 leads to an increase of ... Most studies used analogues of the nucleotide substrates or derivatives of natural product inhibitors such as xanthine (e.g. ... intracellular concentrations of the second messenger cyclic adenosine monophosphate (cAMP). cAMP mediates the phosphorylation ... A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of ...
... activating a type of guanosine nucleotide-binding protein called Gs protein. This type of protein stimulates the production of ... calcium excess: One explanation is most basically due to an increased amount of cyclic AMP(cAMP) in the muscle cells of the ... Phosphodiesterase inhibitors such as caffeine directly affect the G-coupled signal transduction cascade by inhibiting the ... 90 (6): 2843-52. doi:10.1161/01.cir.90.6.2843. PMID 7994829. Belhassen B (2005). "Radiofrequency ablation of "benign" right ...
... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... guanyl-nucleotide exchange factor activity. • RNA binding. Cellular component. • cytoplasm. • ciliary basal body. • centrosome ... "Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: paucity of mutations in the coding ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ...
Single-nucleotide polymorphisms (SNPs) in the P2RX7 receptor gene are associated with an increased risk of bone fracture. The ... There are two types of NTs: Concentrative nucleoside transporters (CNTs): Na+-dependent symporters Equilibrative nucleoside ... the ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and alkaline phosphatases (APs). Extracellular AMP is hydrolyzed ... for sustained platelet aggregation through the inhibition of adenylate cyclase and a corresponding decrease in cyclic adenosine ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ...
... resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of ... A third type of light-sensing cell, the photosensitive ganglion cell, is important for entrainment of circadian rhythms and ... This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, ... There are two types of centre-surround structures in the retina - on-centres and off-centres. On-centres have a positively ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... "Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth ... For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to ... 161 (6): 2798-803. PMID 9743338.. *^ Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF (August 1999 ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ...
Yeast tRNA cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3' end. Yeast tRNA ... exon then performs a nucleophilic attack at the first nucleotide following the last nucleotide of the intron at the 3' splice ... This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts for more than 99% of splicing. ... Splicing occurs in all the kingdoms or domains of life, however, the extent and types of splicing can be very different between ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Type II[edit]. Type II site-specific deoxyribonuclease. Structure of the homodimeric restriction enzyme EcoRI (cyan and green ... Type V[edit]. Type V restriction enzymes (e.g., the cas9-gRNA complex from CRISPRs[43]) utilize guide RNAs to target specific ... Type l[edit]. Type I restriction enzymes were the first to be identified and were first identified in two different strains (K- ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... The third type of glucose 6-phosphatase deficiency, glucose 6-phosphatase-β deficiency, is characterized by a congenital ... 1993). "Glycogen Storage Disease Type I". PMID 20301489.. Cite journal requires ,journal=. (help). ... Chou JY, Matern D, Mansfield BC, Chen YT (March 2002). "Type I glycogen storage diseases: disorders of the glucose-6- ...
Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound ... One type of photosensitive pigment Three types of photosensitive pigment in humans ... Each transducin then activates the enzyme cGMP-specific phosphodiesterase (PDE).. *PDE then catalyzes the hydrolysis of cGMP to ... resulting in the closure of cyclic nucleotide-gated Na+ ion channels located in the photoreceptor outer segment membrane. ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... LIPE, AOMS4, FPLD6, HSL, LHS, lipase E, hormone sensitive type. External IDs. OMIM: 151750 MGI: 96790 HomoloGene: 3912 ... which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs protein- ... 26 (1): 6-16. doi:10.1038/sj.ijo.0801858. PMID 11791141.. *. Smih F, Rouet P, Lucas S, et al. (2002). "Transcriptional ...
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.[5] ... type 1 angiotensin receptor binding. • protein complex binding. • signal transducer activity. • protein binding. • GTPase ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... retina development in camera-type eye. • Ras protein signal transduction. • cell proliferation. • cellular response to hypoxia ...
3 Types of G protein signaling *3.1 Heterotrimeric G proteins *3.1.1 Common mechanism *3.1.1.1 Activation ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ...
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was ... Involved in growth and metastasis of some types of tumors.[24]. *Used in the endocrine system for peptide and amino-acid ... When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide ... These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates ...
Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ... Types[edit]. There are membrane-bound (type 1, guanylate cyclase-coupled receptor) and soluble (type 2, soluble guanylate ... Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on ... Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ...
This compound is a potent inhibitor of cGMP specific phosphodiesterase type 5, the enzyme that degrades the signalling molecule ... This block of nucleotide biosynthesis is more toxic to rapidly growing cells than non-dividing cells, since a rapidly growing ... cyclic guanosine monophosphate.[40] This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results from an ...
The cyclic AMP-regulatory dimers are degraded by phosphodiesterase and release 5'AMP. DNA in the cell nucleus binds to ... G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • activation of adenylate cyclase ... LHCGR have been found in many types of extragonadal tissues, and the physiologic role of some has remained largely unexplored. ... Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was ...
Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3 ... This α-subunit then activates a phosphodiesterase that catalyzes the conversion of cGMP to GMP, thereby reducing current ... though in some cases the truncated proteins may be able to coassemble with wild-type channels in a dominant negative fashion. ... There are at least four genetic causes of congenital ACHM, two of which involve cyclic nucleotide-gated ion channels (ACHM2/ ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... Phosphodiesterase type 11 (PDE11) is a type of phosphodiesterase enzyme. An inhibitor is BC11-38. ...
Cyclic nucleotide phosphodiesterase. 3.1.6: Sulfatase. *arylsulfatase *Arylsulfatase A. *Arylsulfatase B. *Arylsulfatase E ... 1994). "New type of linkage between a carbohydrate and a protein: C-glycosylation of a specific tryptophan residue in human ... Eosinophil-derived neurotoxin is an enzyme that in humans is encoded by the RNASE2 gene.[5][6][7] ... 63 (6): 715-22. doi:10.1002/jlb.63.6.715. PMID 9620664.. *. Zhang J, Rosenberg HF (2001). "Sequence variation at two eosinophil ...
... acts as a phosphodiesterase (PDE) type-1 inhibitor in isolated rabbit aorta,[12] Independent of vinpocetine's ... Hagiwara M, Endo T, Hidaka H (February 1984). "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle ... As of 2003 only three controlled clinical trials had tested "older adults with memory problems".[6] However, a 2003 Cochrane ... 26-4-2/h5-6,8-9,14,20H,3-4,7,10-13H2,1-2H3/t20-,22+/m1/s1 Y ...
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 ... 9 (6): 299-301. doi:10.1124/mi.9.6.5. PMC 2861806. PMID 20048135. Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, ...
... cyclic AMP, cyclic nucleotide phosphodiesterases, type 1, glucose, humans, insulin, insulin-like growth factor I, islets of ... Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin ... Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin ... 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized ...
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. ...
... guanine nucleotide dissociation inhibitors (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed ... Cyclic Nucleotide Phosphodiesterases, Type 6 / chemistry * Cyclic Nucleotide Phosphodiesterases, Type 6 / metabolism* ... The structure explains the nucleotide-independent binding of Rheb to PDEδ and the relaxed specificity of PDEδ. We demonstrate ... guanine nucleotide dissociation inhibitors (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed ...
Kakkar R, Raju RVS, Sharma RK (1999) Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1). Cell Mol Life Sci 55: ... Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure. Alexandre E. ... Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure ... Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure ...
... cyclic nucleotide-gated channel; HCN channel, hyperpolarization-activated, cyclic nucleotide-gated channel; LTCC, L-type ... A light-induced conformational change of rhodopsin leads to a transducin-mediated activation of phosphodiesterase 6 (PDE6) and ... Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels could be further effectors of presynaptic cGMP. HCN1 ... Biel, M., and Michalakis, S. (2009). Cyclic nucleotide-gated channels. Handb. Exp. Pharamacol. 191, 111-136. ...
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 ... Although the type 1 enzymes are classified as 3,5-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class ... type II (intermediate form), and type III (Kugelberg-Welander disease). Type I is fatal in infancy, type II has a late ...
0 (Zebrafish Proteins); EC 3.1.4.- (Pde6c protein, zebrafish); EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 6). ... PURPOSE: Primary glioblastoma (pGBM) is the most common and lethal type of neoplasms in the central nervous system, while the ... we subjected pde6c and wild-type (WT) retinas at 5 dpf/ 120 h postfertilization (hpf) to RNA sequencing (RNA-Seq) on the ... 6 Tiantan Xili, Dongcheng District, Beijing, 100050, China.. [Ti] T tulo:. A novel gene signature based on five glioblastoma ...
The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases ( ... Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias.. Molina CE, Leroy J, Richter W, ... Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular ... Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia. ...
Cyclic Nucleotide Phosphodiesterases, Type 6/metabolism. *Fibroblast Growth Factor 2/metabolism. *Humans ... B,C) The loss of EDN2 in Tg(RHO P347S) retinas resulted in a mean 63% increase in ONL thickness at PN40 (n = 6; p,0.005) (C) ... B,C) The loss of EDN2 in Tg(RHO P347S) retinas resulted in a mean 63% increase in ONL thickness at PN40 (n = 6; p,0.005) (C) ... and a mean 110% increase in ONL thickness in Pde6brd1/rd1 retinas at PN15 (n = 6; p,0.005) (B). (D) ONL thickness in WT, ...
Cyclic-nucleotide phosphodiesterases. Nonsteroidal antiinflammatory drugs. Neuroblastoma sh-sy5y cells. Binding-protein-beta. ... Phosphodiesterase 7 plays a major role in down-regulation of protein kinase A activity by hydrolyzing cAMP in many cell types. ... This cyclic nucleotide plays a key role in signal transduction in a wide variety of cellular responses. In the brain, cAMP has ... Phosphodiesterase 7 inhibition preserves dopaminergic neurons in cellular and rodent models of Parkinson disease. ...
6]. Zaenglein, A. L. & Thiboutot, D. M., Mar 1 2007, In : Pediatrics. 119, 3, p. 650-651 2 p.. Research output: Contribution to ... 6, p. 1365-1366 2 p.. Research output: Contribution to journal › Letter ...
Emesis induced by inhibitors of type IV cyclic nucleotide phosphodiesterase (PDE IV) in the ferret. Neuropharmacology 1999. 38: ... Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 2001. 108:671-680. View this article via: PubMed CrossRef Google ... The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 2000. 63:1-38. ... Cyclic nucleotides cAMP and cGMP are degraded by at least 11 families of phosphodiesterases (PDEs 1-11) classified according to ...
2008) Transketolase and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase type I isoforms are specifically recognized by IgG ... 2′,3′-cyclic-nucleotide 3′-phosphodiesterase. CNS. central nervous system. MuS. multiple sclerosis. MS/MS. tandem mass ... 1998) Dual implication of 2′,3′-cyclic nucleotide 3′ phosphodiesterase as major autoantigen and C3 complement-binding protein ... 2008) Designed glycopeptides with different beta-turn types as synthetic probes for the detection of autoantibodies as ...
... of the Gαt levels in wild-type rods showed only a sixfold reduction in sensitivity and a threefold decrease in the ... of transducin and an increased activation rate by photoexcited rhodopsin or more efficient activation of cGMP phosphodiesterase ... of the Gαt levels in wild-type rods showed only a sixfold reduction in sensitivity and a threefold decrease in the ... of the Gαt levels in wild-type rods showed only a sixfold reduction in sensitivity and a threefold decrease in the ...
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 ...
type. Contribution to journal publication status. published. subject. *Endocrinology and Diabetes. keywords. human lymphocytes ... Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune ... Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune ... Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes. Ekholm, Dag ...
... aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs ... Activity type: Higher or Secondary Education Establishments. Administrative contact: Joe Galloway. Tel.: +44 141 330 3884. E- ... Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases. From 2014-03-01 to ... Final Report Summary - PDE4NPD (Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic ...
3,5-Cyclic-AMP Phosphodiesterases [D08.811.277.352.640.150]. *Cyclic Nucleotide Phosphodiesterases, Type 3 [D08.811.277.352. ... "Cyclic Nucleotide Phosphodiesterases, Type 3" by people in UAMS Profiles by year, and whether "Cyclic Nucleotide ... Cyclic Nucleotide Phosphodiesterases, Type 2. *Cyclic Nucleotide Phosphodiesterases, Type 3. *Cyclic Nucleotide ... "Cyclic Nucleotide Phosphodiesterases, Type 3" is a descriptor in the National Library of Medicines controlled vocabulary ...
... cyclic-nucleotide 3′-phosphodiesterase (CNP)-eGFP-L10a bacterial artificial chromosome (BAC) transgenic mice and wild-type ... 2008) Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell 135:749-762, doi: ... 2008) A translational profiling approach for the molecular characterization of CNS cell types. Cell 135:738-748, doi:10.1016/j. ... 2004) NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the ...
... often suppressing an acute rise in a given cyclic nucleotide back to baseline within seconds to minutes.2 It is also ... but also by their hydrolysis catalyzed by phosphodiesterases (PDEs). PDE regulation is quite potent, ... the duration and magnitude of these signaling cascades are determined not only by generation of cyclic nucleotides, ... Each cyclic nucleotide has a corresponding primary targeted protein kinase, protein kinase (PK)A for cAMP, and PKG for cGMP. ...
Human cyclic GMP-stimulated 3,5-cyclic nucleotide phosphodiesterase (PDE2A3) cDNAs were cloned from hippocampus and fetal ... Inhibition of cGMP-specific phosphodiesterase type V (PDE5) has been shown to improve penile erection in patients with erectile ... Two cyclic-nucleotide phosphodiesterases (DdPDE 1 and 2) have been identified previously, an extracellular dual-specificity ... We have cloned and characterized the first human isozyme in a new family of cyclic nucleotide phosphodiesterases, PDE9A. By ...
... rat and mouse cAMP phosphodiesterase isoforms (denoted PDE4D7s), as well as the DNA (RNA) encoding such polypeptides, are ... Other types of polynucleotide variants will be evident to one of skill in the art. For example, the nucleotides of a ... and thereby regulate the level of cyclic nucleotides within cells and maintain cyclic nucleotide homeostasis. A subclass of ... Such agents may, e.g., modulate phosphodiesterase activity, or inhibit or enhance cyclic nucleotide hydrolysis. The agents can ...
Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. J Clin Invest. 2006;116(12 ... To further investigate the status of IRS2 Ser388 in type 2 diabetic mouse models, such as db/db mice, that are known to be ... The involvement of IRS2 in the pathogenesis of type 2 diabetes is highlighted by the phenotype of Irs2-/- mice. Indeed, these ... Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 1998;391(6670):900-904.. View this article via: PubMed CrossRef ...
Bevilacqua M, Vago T, Baldi G. Nimesulide inhibits cyclic nucleotide specific phosphodiesterase (PDE; type IV) in human ... Nimesulide decreases superoxide production by inhibiting phosphodiesterase type IV Eur J Pharmacol. In pressGoogle Scholar ... phosphodiesterase type IV inhibition, platelet aggregation and synthesis of platelet activating factor. Animal studies have ... 6.. Verhoeven AJ, Tool ATJ, Kuijpers TW, et al. Nimesulide inhibits platelet-activating factor synthesis in activated human ...
... of Guanylate Cyclase 2e or Cyclic Nucleotide Gated Channel Alpha 1 Increases Photoreceptor Survival in a CGMP Phosphodiesterase ... The murine opsin promoter was used to drive the expression of a mutant N74A and a wild-type PDE6γ control transgene in the ... Pubmed ID: 24101599 Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase-6 (PDE6) are the third ... Oct, 2011 , Pubmed ID: 21616145 The inhibitory subunit of rod cyclic guanosine monophosphate (cGMP) phosphodiesterase, PDE6γ, ...
... a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum ... Francis S H, Turko I V, Corbin J D. Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid ... penis erectile dysfunction icariin nitric oxide phosphodiesterase type 5 JIANG Zhaojian, male, born in 1968, Associate ... Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in ...
Hennessy, J., Clarke, L. E., Ioffreda, M. & Helm, K., Jun 1 2009, In : Journal of Cutaneous Pathology. 36, 6, p. 711-712 2 p.. ... Stanhewicz, A. E., Ferguson, S., Bruning, R. S. & Alexander, L. M., Jan 1 2014, In : JAMA Dermatology. 150, 6, p. 658-660 3 p. ... Helm, T. N. & Helm, K., Jun 1 2018, In : American Journal of Dermatopathology. 40, 6, p. 465-467 3 p.. Research output: ... Sansone, R. A., Lam, C. & Wiederman, M. W., May 1 2010, In : Journal of Opioid Management. 6, 3, p. 159-160 2 p.. Research ...
Maximizing the renal cyclic 3′-5′-guanosine monophosphate system with type V phosphodiesterase inhibition and exogenous ... 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 ... Association of B-type natriuretic peptide activation to left ventricular end-systolic remodeling in organic and functional ...
Phosphodiesterase 4B is essential for lipopolysaccharide-induced CC chemokine ligand 3 production in mouse macrophages.( ... Original Article, Report) by Journal of Medical Sciences; Health, general Gel electrophoresis Analysis Phosphodiesterases ... Biochemistry and physiology of cyclic nucleotide phosphodiesterases: Essential components in cyclic nucleotide signaling. Annu ... Regulation of distinct cyclic AMP-specific phosphodiesterase (phosphodiesterase type 4) isozymes in human monocytic cells. Mol ...
  • 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. (strath.ac.uk)
  • The potential for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by Weiss and Hait. (wikipedia.org)
  • These phosphodiesterase inhibitors are used primarily as remedies for erectile dysfunction, as well as having some other medical applications such as treatment of pulmonary hypertension. (wikipedia.org)
  • Although some studies showed the efficacy of phosphodiesterase (PDE) inhibitors as neuronal plasticity enhancers, little is known about the effectiveness of these drugs to improve plasticity in cases of mental retardation. (jneurosci.org)
  • Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). (nih.gov)
  • Finally, S14 neuroprotective effects were reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase A. [Conclusions/Significance]: Our findings demonstrate that phosphodiesterase 7 inhibition can protect dopaminergic neurons against different insults, and they provide support for the therapeutic potential of phosphodiesterase 7 inhibitors in the treatment of neurodegenerative disorders, particularly Parkinson disease. (csic.es)
  • Such as inhibitors can be used, for example, as a means of increasing cyclic AMP in neurons and thus treating neurological problems, such as long term memory loss, if not preventing such maladies entirely. (freepatentsonline.com)
  • Background: Phosphodiesterase 4 (PDE4) inhibitors negatively modulate many inflammatory responses, and some of these pharmacological effects are mediated by inhibition of PDE4B in inflammatory cells. (thefreelibrary.com)
  • sup][5] By increasing intracellular cAMP level, phosphodiesterase 4 (PDE4) inhibitors are being developed as anti-inflammatory agents for the treatment of chronic inflammatory disorders such as asthma, chronic obstructive pulmonary disease, and psoriasis. (thefreelibrary.com)
  • Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of neuronal plasticity-related genes, neurotrophic factors, and neuroprotective molecules. (frontiersin.org)
  • Compounds according to the invention are potent and selective phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of diseases such as asthma where an unwanted inflammatory response or muscular spasm is present. (freepatentsonline.com)
  • Phosphodiesterase inhibitors in clinical urology. (semanticscholar.org)
  • Treatment opportunities involving phosphodiesterase inhibitors (PDEIs) and purinergic modulators may plausibly exist. (iacfsme.org)
  • In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or N(G)-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. (tudelft.nl)
  • Even though cGMP binding to the catalytic site stimulates cyclic-nucleotide binding to the allosteric [ 5 ] sites, inhibitors do not elicit the same function. (ijddr.in)
  • Currently there are three (Sildenafil, vardenafil and tadalafil) Phosphodiesterase type-5 inhibitors (PDE5-i) used in the treatment of male ED [ 6 ]. (ijddr.in)
  • Aim and Objective: Human full-length cyclic nucleotide phosphodiesterase isozyme 4B2 (hPDE4B2) as the target for screening and characterizing inhibitors suffers from low activity yield and the coexistence of two conformational states bearing different affinities for (R)-rolipram. (eurekaselect.com)
  • Lipworth, B.J. Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. (eurekaselect.com)
  • Pharmacology of phosphodiesterase-5 inhibitors. (consilium-medicum.com)
  • Phosphodiesterase 5 inhibitors: current status and potential applications. (consilium-medicum.com)
  • It was further discovered that prostaglandin analogues synergistically work with phosphodiesterase 3B inhibitors to improve or increase cAMP accumulation and ATP release RBCS. (patentsencyclopedia.com)
  • Poor understanding of the topography of cyclic nucleotide (CN) phosphodiesterase (PDE) catalytic sites compromises development of potent, selective inhibitors for therapeutic use. (aspetjournals.org)
  • Furthermore, a description of recent research on this pathway through the use of phosphodiesterase inhibitors is emphasized. (intechopen.com)
  • The PDE4 inhibitors (R)-rolipram, (S)-rolipram (15), and 6-(4Cpyridylmethyl" )-8-(3Cnitrophenyl)quinoline (PMNPQ) (24) had been synthesized at Merck Analysis Laboratories (Montreal, Quebec, Canada). (techuniq.com)
  • The assignments of varied PDEs in the hypnotic aftereffect of the 2-adrenoceptorCmediated anesthetic program had been examined using selective and mixed-type PDE inhibitors. (techuniq.com)
  • Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune functions in lymphoid cells. (lu.se)
  • This project aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs) in the fight for neglected parasitic diseases (NPD). (europa.eu)
  • Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the amplitude and duration of cAMP and cGMP signaling by controlling cyclic nucleotide (cNT) degradation. (pnas.org)
  • Some PDEs such as type 4 are specific for cAMP, while others such PDE5, specific for cGMP ( Beavo, 1995 ). (frontiersin.org)
  • Screening of AMP- and GMP-producing enzymes such as phosphodiesterases (PDEs), ligases, and synthetases would be simplified by the ability to directly detect unmodified nucleoside monophosphates. (nih.gov)
  • The levels of these intracellular cyclic nucleotides are regulated by the cyclases that synthesize and phosphodiesterases (PDEs) that degrades them into inactive metabolite [ 1 ]. (ijddr.in)
  • 8 These and other studies 9,10 also underlined the importance of cAMP phosphodiesterases (PDEs) for the spatiotemporal control of cAMP signals. (ahajournals.org)
  • A large family of enzymes named cyclic nucleotide phosphodiesterases (PDEs) inactivate cAMP and cGMP through their hydrolysis ( 11 - 14 ). (diabetesjournals.org)
  • Several other proteins such as cyclic nucleotide gated ion channels ( 1 ), phosphodiesterases (PDE) ( 2 ), and guanine nucleotide exchange factors (Epac) ( 3 ) bind cAMP. (mcponline.org)
  • The gel can be used for affinity chromatography of various cyclic nucleotide-responsive proteins, especially those which tolerate modification of the 2'-ribose hydroxyl group such as some phosphodiesterases. (biolog.de)
  • A tBLASTn search of the Myxococcus xanthus genome database at The Institute for Genomic Research (TIGR) identified three genes ( pdeA , pdeB , and pdeC ) that encode proteins homologous to 3′,5′-cyclic nucleotide phosphodiesterase. (asm.org)
  • The immunoprecipitated PDE4D and PDE4B proteins had been further discovered by Traditional western blot analysis utilizing a PDE4D-specific mAb, 61D10E (something special from ICOS Corp., Bothell, Washington, USA), 17321-77-6 supplier or a PDE4B-specific polyclonal antibody, K118, respectively. (techuniq.com)
  • 3. The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC(50) 1 - 5 microM), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. (strath.ac.uk)
  • It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor, depending on the dose. (wikipedia.org)
  • Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia. (nih.gov)
  • A combination of pharmacological and genetic approaches was used to determine the role of type 4 cAMP-specific cyclic nucleotide phosphodiesterase 4 (PDE4) in reversing α 2 -adrenoceptor-mediated anesthesia, a behavioral correlate of emesis in non-vomiting species. (jci.org)
  • While inactivation of PDE4B, but not other PDE4 isotypes, is known to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-a) production in macrophages, a cell type critical in mediating innate immunity, the impact of PDE4B on many other inflammatory responses in these cells remains largely unknown. (thefreelibrary.com)
  • Phosphodiesterase 4 (PDE4) is a major enzyme controlling the hydrolysis of cAMP in the brain. (ijbs.com)
  • VSMC cAMP hydrolysis is catalyzed by members of the phosphodiesterase 3 (PDE3) and PDE4 families ( 12 ), whereas VSMC cGMP is inactivated by PDE1 or PDE5 enzymes ( 15 ). (diabetesjournals.org)
  • A combined mix of pharmacological and hereditary approaches was used to look for the function of type 4 cAMP-specific cyclic nucleotide phosphodiesterase 4 (PDE4) in reversing 2-adrenoceptorCmediated anesthesia, a behavioral correlate of emesis in non-vomiting types. (techuniq.com)
  • A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). (wikipedia.org)
  • Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. (nih.gov)
  • Elevation of the second messenger cyclic adenosine monophosphate (cAMP) in macrophages suppresses several inflammatory responses, including inflammatory mediator production and receptor-mediated phagocytosis. (thefreelibrary.com)
  • Phosphodiesterase are enzymes that catalyze the hydrolysis of the 3′ cyclic phosphate bonds of adenosine and/or guanosine 3′, 5′ cyclic monophosphate ( Beavo, 1995 ). (frontiersin.org)
  • It is based on adenosine triphosphate (ATP) and its derivatives, ADP and adenosine as well as the purine nucleotide UTP. (iacfsme.org)
  • There are two important secondary messengers that regulate many physiological processes i.e., 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP). (ijddr.in)
  • Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling. (drugcentral.org)
  • The cyclic adenosine monophosphate (cAMP) signaling controlled by phosphodiesterase (PDE) 4 is a pivotal intracellular modulator for macrophages functions in immune inflammatory response underlying AECOPD as well as obesity and diabetes. (scirp.org)
  • It is well established that inhibition of dipeptidyl peptidase (DPP)-IV reduces glucose levels and preserves pancreatic beta cell function in patients with type 2 diabetes. (bioportfolio.com)
  • Methodology/Principal Findings]: Here we show a novel function of phosphodiesterase 7 inhibition on nigrostriatal dopaminergic neuronal death. (csic.es)
  • Inhibition of cGMP-specific phosphodiesterase type V (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. (embl.de)
  • Nimesulide is a relatively weak inhibitor of prostaglandin synthesis in vitro and appears to exert its effects through a variety of mechanisms including free-radical scavenging, effects on histamine release, the neutrophil myeloperoxidase pathway, bradykinin activity, tumour necrosis factor-α release, cartilage degradation, metalloprotease synthesis, phosphodiesterase type IV inhibition, platelet aggregation and synthesis of platelet activating factor. (springer.com)
  • 1995) Cyclic nucleotide phosphodiesterase type IV participates in the regulation of IL-10 and in the subsequent inhibition of TNF alpha and IL-6 release by endotoxin-stimulated macrophages. (avivasysbio.com)
  • SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. (utmb.edu)
  • a second effect is the inhibition of phosphodiesterases with the subsequent accumulation of cAMP and an intensification of the effects of catecholamines. (uni-kl.de)
  • Although the inhibition of phosphodiesterases may contribute to the actions of caffeine, there is growing evidence that most pharmacological effects of this xanthine result from antagonism of AR. (uni-kl.de)
  • The invention is based upon the discovery that red blood cells contain phosphodiesterase 3B (PDE3B), and that inhibition of that phosphodiesterase allows for an enhanced accumulation of cAMP and subsequent release of ATP. (patentsencyclopedia.com)
  • A vast number of studies have focused on understanding the nitric oxide (NO) signaling pathway, which culminates with the phosphorylation of the transcription factor cAMP-responsive element-binding protein (CREB) through the increase of the second messenger cyclic guanosine monophosphate (cGMP) and activation of cGMP-dependent protein kinase. (intechopen.com)
  • Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. (embl.de)
  • Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type V (PDE5) in rat penis were also observed. (springer.com)
  • After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR). (springer.com)
  • Yonkenafil is a novel phosphodiesterase type 5 (PDE5) inhibitor. (newdrugapprovals.org)
  • When overexpressed in cell cultures, GPR37 tends to become unfAgeded and insoluble, and it tends to lead to unfAgeded protein-induced cell death, whereas the coexpression of parkin specifically ubiquitinylates GPR37 and promotes its proteosomal degradation (6). (lw90.com)
  • This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. (origene.com)
  • The degradation of cAMP is achieved by 3′,5′-cyclic nucleotide phosphodiesterases, which catalyze cleavage of 3′,5′-cAMP to 5′-cAMP. (asm.org)
  • Human, rat and mouse cAMP phosphodiesterase isoforms (denoted PDE4D7s), as well as the DNA (RNA) encoding such polypeptides, are disclosed. (freepatentsonline.com)
  • Lin C S, Lin G, Lue T F. Isolation of two isoforms of phosphodiesterase 5 from rat penis. (springer.com)
  • Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. (nature.com)
  • Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. (unh.edu)
  • Allosteric Regulation of Rod Photoreceptor Phosphodiesterase 6 (PDE6) Elucidated by Chemical Cross-Linking and Quantitative Mass Spectrometry. (unh.edu)
  • Photoreceptor phosphodiesterase (PDE6) is the central effector enzyme in the visual excitation pathway in rod and cone photoreceptors. (unh.edu)
  • To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/δ-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). (edu.sa)
  • Identification and characterization of DdPDE3, a cGMP-selective phosphodiesterase from Dictyostelium. (embl.de)
  • Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. (embl.de)
  • Photoreceptor cGMP phosphodiesterase (PDE6) is the central enzyme in the visual transduction cascade. (unh.edu)
  • Unlike most GAF domain-containing cyclic nucleotide phosphodiesterases, little is known about direct allosteric communication of PDE6. (unh.edu)
  • The third-most common cause of autosomal recessive retinitis pigmentosa (RP) is due to defective cGMP phosphodiesterase-6 (PDE6). (elsevier.com)
  • We solved crystal structures of the phosphodiesterase domain of mouse CNPase, showing the binding mode of nucleotide ligands in the active site. (jove.com)
  • Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular arrhythmias in mice. (nih.gov)
  • Compartmentalization of cardiac beta-adrenergic inotropy modulation by phosphodiesterase type 5. (semanticscholar.org)
  • Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes. (semanticscholar.org)
  • 2-5 Because dysregulation of parasympathetic activity occurs in heart failure, sick sinus syndrome, and selected cardiac arrhythmias, 6 it is of clinical interest to identify key molecular regulators of parasympathetic signaling. (ahajournals.org)
  • Steady-state activation of cardiac β-adrenergic receptors leads to an intracellular compartmentation of cAMP resulting from localized cyclic nucleotide phosphodiesterase (PDE) activity. (ahajournals.org)
  • It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. (drugcentral.org)
  • Cardiac phosphodiesterase 5 (cGMP-specific) modulates b -adrenergic signaling in vivo and is down-regulated in heart failure. (consilium-medicum.com)
  • A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. (uams.edu)
  • 3 Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain. (jci.org)
  • Eleven different PDE gene families have been described and characterized based on their sequences and regulatory properties ( 6 - 8 ). (pnas.org)
  • Context Convergent data make 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) a candidate gene for schizophrenia. (cf.ac.uk)
  • Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. (semanticscholar.org)
  • Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K: A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. (drugbank.ca)
  • In humans disruption of the IL-6 gene may lead to the presentation of rheumatoid arthritis systemic juvenile ( RASJ ), an inflammatory articular disorder manifesting with daily spiking fever, macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. (bio-rad-antibodies.com)
  • A cAMP phosphodiesterase gene ( cpdA )-disrupted Escherichia coli or Salmonella enterica serovar Typhimurium strain showed about 2- or 1.3-fold higher intracellular cAMP than the wild-type strain, respectively ( 2 , 6 ). (asm.org)
  • McDonald L G, Murad F. Nitric oxide and cyclic GMP signaling. (springer.com)
  • Neurogenic relaxation of the internal anal sphincter is mediated by elevation of cyclic GMP, following activation of soluble guanylyl cyclase by nitric oxide. (bmj.com)
  • Endothelium-derived relaxing factors, such as nitric oxide or prostacyclin, relax blood vessels and inhibit the proliferation and migration of VSMCs by increasing the synthesis of the cyclic nucleotides cAMP or cGMP ( 7 - 10 ). (diabetesjournals.org)
  • The structure explains the nucleotide-independent binding of Rheb to PDEδ and the relaxed specificity of PDEδ. (nih.gov)
  • Biochemical data suggest the presence of at least one cGMP-specific phosphodiesterase (PDE) that is activated by cGMP. (embl.de)
  • Only one member of the cAMP and cGMP-specific phosphodiesterase type-10 (PDE10) family is cloned and characterized. (acris-antibodies.com)
  • Retinal Degeneration in Mice Lacking the Gamma Subunit of the Rod CGMP Phosphodiesterase Science (New York, N.Y. (jove.com)
  • Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. (uniprot.org)
  • Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. (uniprot.org)
  • Sildenafil: an orally type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. (nature.com)
  • Importantly, TbrPPX1 does not exhibit any cyclic nucleotide specific phosphodiesterase activity, which definitively eliminates it as an additional player in cAMP signalling of the kinetoplastida. (biomedcentral.com)
  • Background]: Phosphodiesterase 7 plays a major role in down-regulation of protein kinase A activity by hydrolyzing cAMP in many cell types. (csic.es)
  • The inhibitory effect of rolipram on CCL3 production was mimicked by the protein kinase A activator 6-Bnz-cAMP, but not the exchange protein directly activated by cAMP activator 8-pCPT-2'-O-Me-cAMP. (thefreelibrary.com)
  • p>This indicates the type of evidence that supports the existence of the protein. (uniprot.org)
  • 2] Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. (axonmedchem.com)
  • By contrast, Gα i/o can both modulate phosphodiesterase activity and inhibit adenylyl cyclase activity, reduce both intracellular cAMP levels and protein kinase A activity, leading to decreased depolarizing currents carried by HCN and L-type calcium channels. (ahajournals.org)
  • The human protein functions in the cellular export of its substrate, cyclic nucleotides. (origene.com)
  • Studies show that the human protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. (origene.com)
  • 2. Calmodulin activated cyclic AMP or cyclic GMP PDE activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. (strath.ac.uk)
  • IL-6 is a potent lymphoid cell growth factor which is principally expressed by macrophages and T-cells. (avivasysbio.com)
  • Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. (nature.com)
  • IL-6 is a potent inducer of the acute phase response. (bio-rad-antibodies.com)
  • Pubmed ID: 8638127 The retinal cyclic guanosine 3',5'-monophosphate (cGMP) phosphodiesterase (PDE) is a key regulator of phototransduction in the vertebrate visual system. (jove.com)
  • To address this need, we developed polyclonal and monoclonal antibodies that recognize AMP and GMP with nanomolar sensitivity and high selectivity vs. the corresponding triphosphate and 3',5'-cyclic monophosphate nucleotides that serve as substrates for many enzymes in these classes. (nih.gov)
  • Two cyclic-nucleotide phosphodiesterases (DdPDE 1 and 2) have been identified previously, an extracellular dual-specificity enzyme and an intracellular cAMP-specific enzyme (encoded by the psdA and regA genes respectively). (embl.de)
  • The 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) is a highly abundant membrane-associated enzyme in the myelin sheath of the vertebrate nervous system. (jove.com)
  • Since the activity of the cyclic nucleotide is also regulated by phosphodiesterase 5, we have examined the effect of zaprinast, an inhibitor of the enzyme, on the sheep isolated internal anal sphincter. (bmj.com)
  • 6. An isolated polynucleotide comprising the nucleotide sequence of the cDNA contained in ATCC deposit numbers PTA-3893, PTA-3894, PTA-3895, or of a fragment thereof. (freepatentsonline.com)
  • 6. An isolated nucleic acid molecule according to claim 1, wherein the molecule comprises the nucleic acid sequence shown in SEQ ID No: 16. (google.es)
  • 7. A recombinant nucleic acid molecule comprising a promoter sequence operably linked to a nucleic acid molecule according to claim 6. (google.es)
  • Note that the complete sequence of our molecular clones may differ from the sequence published for this corresponding reference, e.g., by representing an alternative RNA splicing form or single nucleotide polymorphism (SNP). (origene.com)
  • Therefore, Refseq is one curated sequence, not to be perceived as the wild type. (origene.com)
  • We have cloned and characterized the first human isozyme in a new family of cyclic nucleotide phosphodiesterases, PDE9A. (embl.de)
  • 1] Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases: a diverse family of regulatory enzymes. (axonmedchem.com)
  • Phosphodiesterase isoenzymes in the human urethra: a molecular biology and functional study. (semanticscholar.org)
  • Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) to microbial infection constitutes an evolutionarily ancient type of immunity that is characteristic of all multicellular eukaryotic systems. (uni-tuebingen.de)
  • As a result, cAMP-regulated effectors such as hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, delayed rectifier, and voltage-gated Ca 2+ channels are enlisted by sympathetic activity to increase pacemaker cell firing rate. (ahajournals.org)
  • Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. (uniprot.org)
  • Rat anti Mouse Interleukin-6 antibody, clone MP5-20F3 recognizes mouse Interleukin 6 (IL-6). (avivasysbio.com)
  • Rat anti Mouse Interleukin-6 antibody, clone MP5-20F3 may be used to neutralize IL-6 bioactivity in a functional assay (Abrams et al. (avivasysbio.com)
  • Rat anti Mouse interleukin-6 antibody, clone MP5-20F3 ( MCA1490 ) used to demonstrate IL-6 expression in mouse aortic root by immunofluorescence. (bio-rad-antibodies.com)
  • Rat anti Mouse Interleukin-6 antibody, clone MP5-20F3 recognizes mouse Interleukin 6 (IL-6), also known as B-cell hybridoma growth factor or Interleukin HP-1. (bio-rad-antibodies.com)
  • Wang H, Gaur U, Xiao J, Xu B, Xu J, Zheng W. Targeting phosphodiesterase 4 as a potential therapeutic strategy for enhancing neuroplasticity following ischemic stroke. (ijbs.com)
  • The bisquaternary mono-oximes HS-6 and HI-6 may both be considered as potential therapeutic agents for soman intoxication. (tudelft.nl)
  • Zhang, K.Y. Keynote review: Phosphodiesterase-4 as a therapeutic target. (eurekaselect.com)
  • Murad F. Cyclic GMP: synthesis, metabolism, and function. (springer.com)
  • Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. (tudelft.nl)
  • Waldman SA, Murad F . Cyclic GMP synthesis and function. (nature.com)
  • Measuring CD38 Hydrolase and Cyclase Activities: 1,N(6)-Ethenonicotinamide Adenine Dinucleotide (epsilon-NAD) and Nicotinamide Guanine Dinucleotide (NGD) Fluorescence-based Methods. (mayo.edu)
  • GPR37 has been recently Displayn to be a substrate of parkin and termed parkin-associated enExecutethelin-like receptor (6). (lw90.com)
  • We found that S14, a heterocyclic small molecule inhibitor of phosphodiesterase 7, conferred significant neuronal protection against different insults both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. (csic.es)
  • Moreland RB, Goldstein I, Traish A . Sildenafil, a novel inhibitor of phosphodiesterase type 5 human corpus cavernosum smooth muscle cells. (nature.com)
  • Effects OF Sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. (springer.com)
  • Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. (nature.com)
  • Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases. (semanticscholar.org)
  • Soderling S H, Beavo J A. Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. (springer.com)
  • OBJECTIVE The following study was performed to evaluate the importance of phosphodiesterases 3A (PDE3A) and 5A (PDE5A) for the regulation of penile smooth muscle tone. (semanticscholar.org)
  • Cyclic GMP phosphodiesterases and regulation of smooth muscle function. (consilium-medicum.com)
  • Tissue distribution of phosphodiesterase families and the effect of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. (consilium-medicum.com)
  • Yet, it was demonstrated for the first time in vivo that moderate consumption of coffee can modulate the activity of platelet phosphodiesterases in humans in long and short term. (uni-kl.de)
  • 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)
  • Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice. (semanticscholar.org)
  • It has been found that HI-6 was superior to an equal dose of HS-6 in the treatment of soman intoxication in mice and rats. (tudelft.nl)
  • Conscious freely moving RGS4-null mice showed increased bradycardic responses to parasympathetic agonists compared to wild-type animals. (ahajournals.org)
  • Methods: Thirty mice were randomized into 5 groups (G) of 6 animals each. (bvsalud.org)
  • First, as for the metabolic aspects, HFD induced increased glucose level in oral glucose tolerance test (OGTT), homeostasis model assessment-insulin resistance (HOMA-IR) index and mRNA expression of inflammation-related genes including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and IL-6 were reversed in sEH-KO mice. (ncl.edu.tw)
  • Open up in another window Amount 1 Aftereffect of MK-912 over the duration of anesthesia induced with the mix of xylazine (10 mg/kg) and ketamine (80 mg/kg) in C57BL/6 mice. (techuniq.com)
  • Subfamily 1 includes the bacterial RecJ nucleases, while subfamily 2 members fall into three functional groups, the pyrophosphatases, the exopolyphosphatases and the closely related "prune-type" exopolyphosphatases. (biomedcentral.com)
  • A link between an "activated" phenotype of VSMC in diabetes and atherosclerosis has been documented in animal models and humans ( 6 ). (diabetesjournals.org)
  • The baseline luciferase activity in PC-3 cells transfected with the wild-type DR5 reporter was significantly augmented in cells transfected with DR5 constructs carrying deletions or mutation in the YY1-binding site. (aacrjournals.org)
  • Treatment with drug enhanced DR5 wild-type luciferase activity, with no increase in cells transfected with the YY1-deleted or YY1-mutated constructs. (aacrjournals.org)
  • Earlier work has suggested that a human exopolyphosphatase, Prune, might exhibit cyclic nucleotide phosphodiesterase activity. (biomedcentral.com)
  • Finally, the study investigates the potential cyclic nucleotide phosphodiesterase activity of TbrPPX1. (biomedcentral.com)
  • Caffeine and low substituted pyrazines showed no effect on the HO-activity, while NMP, pyrazines with a greater substitution pattern such as Tetramethylpyrazine (TMP) and 2-Ethyl-3,5(6)-dimethylpyrazine (2-E-3,5-DMP) and both coffee extracts significantly induced the HO-activity in liver hepatocellular carcinoma (HepG2), intestinal colo-rectal adenocarcinoma (Caco-2) and in some instances in monocytic leukemia (MM6) cells. (uni-kl.de)
  • It was found that caffeine, theophylline, coffee extracts from conventional or functional coffees, pyrazines (2,3-DE-6-MP, 2-Isobutyl-3-methoxyP), 5-CQA and caffeic acid all significantly inhibited the basal cytoplasmatic PDE activity in lysates of lung tumour xenograft cells (LXFL529L) and human platelets. (uni-kl.de)
  • littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. (diabetesjournals.org)
  • PDE activity was evaluated 17321-77-6 supplier in the lack (total activity) or existence of 10 M rolipram (rolipram-insensitive activity). (techuniq.com)
  • The feasibility of using multipotent neural precursors to replace diseased neurons was tested in adult mouse neocortex with experimentally induced neurodegeneration using the approach of targeted photolytic neuronal degeneration ( 2 - 6 ). (pnas.org)
  • Neuronal degeneration that is spatially defined and cell population-specific can be produced by noninvasive photoactivation of retrogradely transported nanospheres carrying the photoactive chromophore chlorin e 6 within targeted pyramidal neurons in lamina II/III with trans-callosal projections. (pnas.org)
  • These results suggest that mutant forms of parkin may be unable to Accurately interact with unfAgeded GPR37, leading to intracellular GPR37 aggregation and to selective death of SN Executepaminergic neurons, as observed in autosomal recessive inherited juvenile Parkinsonism (6). (lw90.com)
  • cAMP can influence cell growth, differentiation, and movement as well as regulating specialized actions unique to specific cell types. (mcponline.org)
  • To evaluate the time course of the cAMP changes in the different compartments, brief (15 seconds) pulses of isoprenaline (100 nmol/L) were applied to adult rat ventricular myocytes (ARVMs) while monitoring cAMP changes beneath the membrane using engineered cyclic nucleotide-gated channels and within the cytosol with the fluorescence resonance energy transfer-based sensor, Epac2-camps. (ahajournals.org)
  • cAMP kinetics in the two compartments were compared to the time course of the L-type Ca 2+ channel current ( I Ca,L ) amplitude. (ahajournals.org)
  • Indeed, the presence of subcellular compartments with different cAMP concentrations, also called cAMP microdomains, are inferred from L-type Ca 2+ channel current ( I Ca,L ) measurements in response to local β-AR stimulation in cardiomyocytes 5 and by direct monitoring of cAMP using fluorescence resonance energy transfer (FRET)-based sensors 6,7 or cyclic nucleotide-gated (CNG) channels. (ahajournals.org)
  • One of the many phosphodiesterases that compartmentalized and hydrolyze cAMP and cGMP in to AMP and GMP respectively are phosphodiesterase type 10. (acris-antibodies.com)
  • Likewise, RBCS of patients suffering from type 2 diabetes (hyperinsulinemia) accumulate significantly less cAMP and release significantly less ATP than normal RBCS. (patentsencyclopedia.com)
  • Intracellular cyclic AMP (cAMP) levels of pdeA or pdeB mutant cells under these stressful conditions were about 1.3-fold to 2.0-fold higher than those of wild-type cells. (asm.org)
  • We also report that an M. xanthus CbpB containing two cyclic AMP (cAMP)-binding domains is involved in osmotic and temperature tolerance ( 11 ). (asm.org)
  • They are essential regulators of cyclic nucleotide signaling with diverse physiological functions. (axonmedchem.com)
  • Any extracellular stimulation causes a rapid change in the level of cyclic nucleotide, producing the physiological responses elicited by the stimulus. (ijddr.in)
  • Implant-type tissue-engineered cartilage derived from human auricular chondrocyte may maintain cartilaginous property even under osteoinductive condition. (bioportfolio.com)
  • There are 11 human cyclic nucleotide phosphodiesterase (PDE) families. (aspetjournals.org)
  • Free Rp-cAMPS is not metabolized by mammalian phosphodiesterases and thus represents an extraordinary stable ligand. (biolog.de)
  • 1993) Immunocytochemical evidence that S-100- positive cells of the mouse anterior pituitary contain Interleukin-6 immunoreactivity. (avivasysbio.com)
  • Monocytes are peripheral immune cells that have the potential to differentiate into a variety of cell types depending on the combination of cytokines and stimuli to which they are exposed. (pnas.org)
  • The differentiated cell types range from professional antigen-presenting dendritic cells to osteoclasts to various macrophage populations found throughout the body ( 1 - 3 ). (pnas.org)
  • 2',3'-Cyclic nucleotide 3'-phosphodiesterase is used as a marker of myelin-forming cells and is detectable in cells of oligodendrocyte lineage throughout life. (cf.ac.uk)
  • Immunohistochemical labeling has Displayn that, whereas most of the mouse GPR37-positive cells are 2′,3′-cyclic nucleotide 3′-phosphodiesterase-positive oligodendrocytes of fiber tracts, they also include distinct populations of neurons such as the SN Executepaminergic neurons, hippocampal neurons in the CA3 Location, and cerebellar Purkinje cells (6). (lw90.com)
  • About 10 5 to 10 6 cells migrate to an aggregation focus, where they construct a fruiting body. (asm.org)
  • The cbpB mutant was more sensitive to osmotic stress than wild-type cells were, and when cultured under high- or low-temperature conditions, the cbpB mutant exhibited a marked reduction in growth compared to wild-type cells. (asm.org)
  • Corbin J D, Francis S H, Webb D J. Phosphdiesterase type 5 as a pharmacologic target in erectile dysfunction. (springer.com)