Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Cyclic Nucleotide Phosphodiesterases, Type 4: A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.Cyclic Nucleotide Phosphodiesterases, Type 3: A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.Cyclic Nucleotide Phosphodiesterases, Type 1: A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.Cyclic Nucleotide Phosphodiesterases, Type 2: A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), members of this class have additional specificity for CYCLIC GMP.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.2',3'-Cyclic-Nucleotide Phosphodiesterases: Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.Cyclic Nucleotide Phosphodiesterases, Type 5: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.Rolipram: A phosphodiesterase 4 inhibitor with antidepressant properties.PurinonesCyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Dibutyryl Cyclic GMP: N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.Cyclic Nucleotide Phosphodiesterases, Type 7: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.Nucleotides, Cyclic1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESGuanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.Phosphodiesterase 4 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 4.Phosphodiesterase 3 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 3.Phosphorus-Oxygen Lyases: Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.Phosphodiesterase I: A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Pyrrolidinones: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Phosphodiesterase 5 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 5.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.Kinetics: The rate dynamics in chemical or physical systems.Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Cyclic P-OxidesVinca Alkaloids: A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Glycerylphosphorylcholine: A component of PHOSPHATIDYLCHOLINES or LECITHINS, in which the two hydroxy groups of GLYCEROL are esterified with fatty acids. (From Stedman, 26th ed) It counteracts the effects of urea on enzymes and other macromolecules.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.OxadiazolesCatalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Rod Cell Outer Segment: The portion of a retinal rod cell situated between the ROD INNER SEGMENT and the RETINAL PIGMENT EPITHELIUM. It contains a stack of photosensitive disk membranes laden with RHODOPSIN.Xanthines: Purine bases found in body tissues and fluids and in some plants.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Pyrophosphatases: A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position.Photoreceptor Cells: Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)SulfonesDose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.A Kinase Anchor Proteins: A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Receptors, Atrial Natriuretic Factor: Cell surface proteins that bind ATRIAL NATRIURETIC FACTOR with high affinity and trigger intracellular changes influencing the behavior of cells. They contain intrinsic guanylyl cyclase activity.Dictyostelium: A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.Aorta, Thoracic: The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.S-Nitroso-N-Acetylpenicillamine: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Arginine: An essential amino acid that is physiologically active in the L-form.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Carbolines: A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles.QuinoxalinesQuinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Molsidomine: A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS.GMP Reductase: An enzyme that catalyzes the reversible oxidation of inosine 5'-phosphate (IMP) to guanosine 5'-phosphate (GMP) in the presence of AMMONIA and NADP+. This enzyme was formerly classified as EC 1.6.6.8.Nitric Oxide Donors: A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Rana catesbeiana: A species of the family Ranidae (true frogs). The only anuran properly referred to by the common name "bullfrog", it is the largest native anuran in North America.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)Adenine NucleotidesCytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Cyclic GMP-Dependent Protein Kinase Type I: A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.PiperazinesAminoquinolines: Quinolines substituted in any position by one or more amino groups.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Dinucleoside Phosphates: A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Nitroso CompoundsNatriuretic Peptides: Peptides that regulate the WATER-ELECTROLYTE BALANCE in the body, also known as natriuretic peptide hormones. Several have been sequenced (ATRIAL NATRIURETIC FACTOR; BRAIN NATRIURETIC PEPTIDE; C-TYPE NATRIURETIC PEPTIDE).Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cyclic Nucleotide Phosphodiesterases, Type 6: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase.Bacterial Proteins: Proteins found in any species of bacterium.Natriuretic Peptide, C-Type: A PEPTIDE of 22 amino acids, derived mainly from cells of VASCULAR ENDOTHELIUM. It is also found in the BRAIN, major endocrine glands, and other tissues. It shares structural homology with ATRIAL NATRIURETIC FACTOR. It has vasorelaxant activity thus is important in the regulation of vascular tone and blood flow. Several high molecular weight forms containing the 22 amino acids have been identified.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.S-Nitrosoglutathione: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.Chromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Myocardial Contraction: Contractile activity of the MYOCARDIUM.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Molecular Weight: The sum of the weight of all the atoms in a molecule.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Time Factors: Elements of limited time intervals, contributing to particular results or situations.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Trazodone: A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309)Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Fluorescence Resonance Energy Transfer: A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING.Organic Chemistry Phenomena: The conformation, properties, reaction processes, and the properties of the reactions of carbon compounds.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.IndazolesNitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Aorta: The main trunk of the systemic arteries.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Bufo marinus: A species of the true toads, Bufonidae, becoming fairly common in the southern United States and almost pantropical. The secretions from the skin glands of this species are very toxic to animals.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Light: That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Guanine NucleotidesConserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Inosine Triphosphate: Inosine 5'-(tetrahydrogen triphosphate). An inosine nucleotide containing three phosphate groups esterified to the sugar moiety. Synonym: IRPPP.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Biofilms: Encrustations, formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedding in extracellular polymers, that adhere to surfaces such as teeth (DENTAL DEPOSITS); PROSTHESES AND IMPLANTS; and catheters. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and antifouling agents.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Transducin: A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Amino Acid Oxidoreductases: A class of enzymes that catalyze oxidation-reduction reactions of amino acids.Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Oxyhemoglobins: A compound formed by the combination of hemoglobin and oxygen. It is a complex in which the oxygen is bound directly to the iron without causing a change from the ferrous to the ferric state.Methacholine Compounds: A group of compounds that are derivatives of beta-methylacetylcholine (methacholine).Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra.Protoveratrines: Mixtures of closely related hypotensive alkaloids from Veratrum album (Liliaceae). They have been used in the treatment of hypertension but have largely been replaced by drugs with fewer adverse effects.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.
... cyclic-AMP and -GMP phosphodiesterase 11A is an enzyme that in humans is encoded by the PDE11A gene. The 3',5'-cyclic ... Yuasa K, Ohgaru T, Asahina M, Omori K (2001). "Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A): ... Beavo JA, Conti M, Heaslip RJ (1994). "Multiple cyclic nucleotide phosphodiesterases". Mol. Pharmacol. 46 (3): 399-405. PMID ... cyclic nucleotide phosphodiesterase 11A: localization in human tissues". Int. J. Impot. Res. 17 (4): 320-5. doi:10.1038/sj.ijir ...
... cyclic di-GMP). Degradation of cyclic di-GMP to guanosine monophosphate (GMP) is catalyzed by a phosphodiesterase (PDE). ... Cyclic di-GMP binds to interface between the DGC and D2 domains stabilizing the open structure and preventing catalysis. Strong ... Often, GGDEF domains with DGC activity are found in the same proteins as c-di-GMP-specific phosphodiesterase (PDE) EAL (Glu-Ala ... D'Argenio, D.A.; Miller, S.I. (2004). "Cyclic di-GMP as a bacterial second messenger". Microbiology. 150 (Pt 8): 2497-502. doi: ...
... cyclic-GMP phosphodiesterase MeSH D08.811.277.352.640.150 --- 3',5'-cyclic-nucleotide phosphodiesterase MeSH D08.811.277.352. ... cyclic gmp-dependent protein kinases MeSH D08.811.913.696.620.682.700.150.575 --- protamine kinase MeSH D08.811.913.696.620.682 ... cyclic-nucleotide phosphodiesterases MeSH D08.811.277.352.640.295 --- glycerophosphoinositol inositolphosphodiesterase MeSH ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 --- cyclic amp-dependent protein kinases ...
Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are cGMP ... Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second ... cyclic monophosphate (8-Br-cGMP) Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: ... Phosphodiesterase inhibitors prevent the degradation of cGMP, thereby enhancing and/or prolonging its effects. For example, ...
1975). "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic ... June 1997). "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ... The PDE2 (phosphodiesterase 2) enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs ...
... a Specific Inhibitor of Cyclic GMP Phosphodiesterase, on Human Platelet Aggregation". The Journal of Pharmacology and ... Aubin, C; Webster, L; Rebeyka, IM; Ross, DB; Light, PE; Dyck, JR; Michelakis, ED (17 July 2007). "Phosphodiesterase Type 5 is ... MY-5445 is a relatively specific phosphodiesterase 5 inhibitor. Vatalanib - a structurally related angiogenesis inhibitor ... and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility" (PDF). Circulation. 116 (3): 238-48. doi:10.1161/ ...
Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. EMBO J.. 2000;19(20):5288-99 ... In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 ... The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. Proc. Natl. Acad. Sci. U.S ... The GAF domain is named after some of the proteins it is found in: cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA ...
... phosphate phosphodiesterase, cyclic GMP phosphodiesterase, cyclic 3',5'-GMP phosphodiesterase, cyclic guanosine 3',5'- ... Cyclic AMP and cyclic GMP phosphodiesterase". Biochim. Biophys. Acta. 334: 368-377. doi:10.1016/0005-2744(74)90180-6. Molecular ... cyclic-GMP phosphodiesterase (EC 3.1.4.35) is an enzyme that catalyzes the chemical reaction guanosine 3',5'-cyclic phosphate ... phosphate phosphodiesterase, cGMP phosphodiesterase, cGMP-PDE, and cyclic guanosine 3',5'-phosphate phosphodiesterase. As of ...
The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) and cyclic ... cAMP's role in this process terminates upon hydrolysis to AMP by phosphodiesterase. Cyclic nucleotides are well-suited to act ... Lincoln, TM; Cornwell TL (1991). "Towards an understanding of the mechanism of action of cyclic AMP and cyclic GMP in smooth ... As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' ...
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 ... phosphodiesterases. Other advantages of the unique 2'-5' linkage may be that cGAMP is able to bind multiple allelic variants of ... Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). ... "Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses". Science 23 August 2013: Vol. 341 no. 6148 pp ...
1975). "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic ... The PDE2 (phosphodiesterase 2) enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs ... 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. ...
"Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10". Cytogenetics and Cell ... and kinase-directed regulation of phosphorylation of a cGMP-binding phosphodiesterase by cGMP". The Journal of Biological ... 96 (5): 2467-72. doi:10.1073/pnas.96.5.2467. PMC 26808 . PMID 10051666. Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Krämer A ... 27 (3 Pt 2): 552-7. doi:10.1161/01.hyp.27.3.552. PMID 8613202. Salih E, Zhou HY, Glimcher MJ (Jul 1996). "Phosphorylation of ...
... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... 38 (13): 2750-5. PMID 9418727. Yan D, Swain PK, Breuer D, Tucker RM, Wu W, Fujita R, Rehemtulla A, Burke D, Swaroop A (Jul 1998 ... 5 (7): 1035-41. doi:10.1093/hmg/5.7.1035. PMID 8817343. Murga-Zamalloa CA, Atkins SJ, Peranen J, Swaroop A, Khanna H (Sep 2010 ...
Linari M, Hanzal-Bayer M, Becker J (Sep 1999). "The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta, ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... cyclic phosphodiesterase subunit delta is an enzyme that in humans is encoded by the PDE6D gene. PDE6D was originally ...
... c-di-GMP-specific phosphodiesterase, c-di-GMP phosphodiesterase, phosphodiesterase, phosphodiesterase A1, PDEA1, VieA) is an ... Cyclic-guanylate-specific phosphodiesterase (EC 3.1.4.52, cyclic bis(3->5')diguanylate phosphodiesterase, ... "Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP". J. Biol. ... Cyclic-guanylate-specific phosphodiesterase at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular ...
Kroll S, Phillips WJ, Cerione RA (March 1989). "The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of the ... 3'5'-cyclic nucleotide phosphodiesterases (EC 3.1.4.17, cyclic 3',5'-mononucleotide phosphodiesterase, PDE, cyclic 3',5'- ... monophosphate phosphodiesterase (cyclic CMP), cyclic 3',5-nucleotide monophosphate phosphodiesterase, nucleoside 3',5'-cyclic ... cyclic CMP As per Andrew T. Bender and Joseph A. Beavo, there are 11 distinct phosphodiesterase families (PDE1-PDE11) with a ...
... cyclic GMP) from guanosine triphosphate (GTP). The soluble cGMP activates cyclic nucleotide-dependent protein kinase G (PKG or ... This is the biological basis of sildenafil (Viagra), which works to inhibit the enzyme phosphodiesterase PDE5, which lowers the ... 5 (6): 417-471. PMID 10390607. Radicals for life: The various forms of nitric oxide. E. van Faassen and A. Vanin, eds. Elsevier ... 5 (6): 417-41. PMID 10390607. Gu, Qilin; Yang, Xiaojie; Lin, Li; Li, Shaoyang; Li, Qing; Zhong, Shan; Peng, Jinrong; Cui, ...
Cyclic GMP binds to the cGMP-dependent protein kinase (PKG1) which phosphorylates several proteins that results in decreased ... Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine ... GMP is an inactive molecule with no second messenger activity. Phosphorylation of a single serine by PKG1 and the allosteric ...
... 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 ... CMP-N-acylneuraminate phosphodiesterase EC 3.1.4.41: sphingomyelin phosphodiesterase D EC 3.1.4.42: glycerol-1,2-cyclic- ... glucose-1-phospho-D-mannosylglycoprotein phosphodiesterase EC 3.1.4.52: cyclic-guanylate-specific phosphodiesterase EC 3.1.4.53 ... cyclic-nucleotide phosphodiesterase EC 3.1.4.18: now EC 3.1.16.1 EC 3.1.4.19: now EC 3.1.13.3 EC 3.1.4.20: now EC 3.1.13.1 EC ...
... cyclic phosphodiesterase subunit alpha is an enzyme that in humans is encoded by the PDE6A gene. PDE6A encodes the cyclic-GMP ( ... cGMP) specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 ... "Entrez Gene: PDE6A phosphodiesterase 6A, cGMP-specific, rod, alpha". Pittler SJ, Baehr W (1991). "The molecular genetics of ... Catty P, Pfister C, Bruckert F, Deterre P (1992). "The cGMP phosphodiesterase-transducin complex of retinal rods. Membrane ...
... protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in ... Phosphodiesterase inhibitors (e.g., sildenafil) can also improve [Raynaud's phenomenon] symptoms and ulcer healing "Viagra and ... Laties, AM (January 2009). "Vision Disorders and Phosphodiesterase Type 5 Inhibitors: a Review of the Evidence to Date". Drug ... Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for ...
... cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ...
... cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... alkylglycerophosphoethanolamine phosphodiesterase activity. • macromolecular complex binding. Cellular component. • ... 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] ... This gene uses alternative polyadenylation signals.[5][6] Interactive pathway map[edit]. Click on genes, proteins and ...
... cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... An example is adenylate cyclase, which produces the second messenger cyclic AMP.[6] For this discovery, they won the 1994 Nobel ... 3 Types of G protein signaling *3.1 Heterotrimeric G proteins *3.1.1 Common mechanism *3.1.1.1 Activation ...
... cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... doi:10.1016/S0969-2126(01)00259-3. PMID 8591034.. *^ Davies TG, Tunnah P, Meijer L, Marko D, Eisenbrand G, Endicott JA, Noble ... 9 (1): 22-3. doi:10.4161/cc.9.1.10735. PMID 20016257.. *^ Baumann K (November 2013). "Cell cycle: Cyclin A corrections". Nature ... cyclin D 1,2,3 (Cdk4, Cdk6) cyclin E (Cdk2) cyclin A (Cdk2, Cdk1) cyclin B (Cdk1) ...
Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound ... Each transducin then activates the enzyme cGMP-specific phosphodiesterase (PDE).. *PDE then catalyzes the hydrolysis of cGMP to ... GMP via PDE), resulting in the closure of cyclic nucleotide-gated Na+ ion channels located in the photoreceptor outer segment ... In the dark, cells have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which opens ion ...
... phosphate phosphodiesterase, cyclic GMP phosphodiesterase, cyclic 3,5-GMP phosphodiesterase, cyclic guanosine 3,5- ... Cyclic AMP and cyclic GMP phosphodiesterase". Biochim. Biophys. Acta. 334: 368-377. doi:10.1016/0005-2744(74)90180-6. Molecular ... cyclic-GMP phosphodiesterase (EC 3.1.4.35) is an enzyme that catalyzes the chemical reaction guanosine 3,5-cyclic phosphate ... phosphate phosphodiesterase, cGMP phosphodiesterase, cGMP-PDE, and cyclic guanosine 3,5-phosphate phosphodiesterase. As of ...
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. ... Catalyzes the hydrolysis of both cAMP and cGMP to 5-AMP and 5-GMP, respectively (By similarity). ... cGMP-stimulated cyclic-nucleotide phosphodiesterase activity Source: UniProtKB. *cyclic-nucleotide phosphodiesterase activity ... cyclic-AMP and -GMP phosphodiesterase 11AAdd BLAST. 933. Amino acid modifications. Feature key. Position(s). DescriptionActions ...
... cyclic monophosphate (cGMP) synthesis counters this response. Here, we show that blocking the intrinsic catabolism of c … ... Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy Nat Med. 2005 Feb;11(2):214-22. ... Here, we show that blocking the intrinsic catabolism of cGMP with an oral phosphodiesterase-5A (PDE5A) inhibitor (sildenafil) ... Genetically engineered hyperstimulation of guanosine 3,5-cyclic monophosphate (cGMP) synthesis counters this response. ...
... cyclic phosphodiesterase subunit delta - EC 3.1.4.17; GMP-PDE delta; p17 protein \ 10-288-22226F for more molecular products ... cyclic phosphodiesterase subunit delta - EC 3.1.4.17; GMP-PDE delta; p17 protein ... cyclic phosphodiesterase subunit delta - EC 3.1.4.17; GMP-PDE delta; p17 protein Related products : Retinal rod rhodopsin- ... cyclic phosphodiesterase subunit delta - EC 3.1.4.17; GMP-PDE delta; p17 protein / Product Detail : 10-288-22226F Retinal rod ...
J:32329 Tuteja N, et al., Gamma-subunit of mouse retinal cyclic-GMP phosphodiesterase: cDNA and corresponding amino acid ... 5 phenotypes from 1 allele in 1 genetic background 2 phenotypes from multigenic genotypes 18 phenotype references ...
... cyclic-GMP phosphodiesterase activity Source: UniProtKB-EC. *cGMP binding Source: InterPro. View the complete GO annotation on ... cyclic phosphodiesterase subunit gammaAdd BLAST. 87. Amino acid modifications. Feature key. Position(s). DescriptionActions. ... cyclic phosphodiesterase subunit gamma OS=Canis lupus familiaris OX=9615 GN=PDE6G PE=3 SV=1 ... p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and ...
... cyclic-GMP phosphodiesterase) inhibitor (CHEBI:71942) tadalafil (CHEBI:71940) has role vasodilator agent (CHEBI:35620) ... cyclic-GMP phosphodiesterase) inhibitor An EC 3.1.4.* (phosphoric diester hydrolase) inhibitor that blocks the action of 3,5- ... A phosphodiesterase V inhibitor inhibitor, currently marketed in pill form for treating erectile dysfunction under the name ... BENZO[1,3]DIOXOL-. 5-. YL-. 2-. METHYL-. 2,3,6,7,12,12A-. HEXAHYDRO-. PYRAZINO[1,2:1,6]PYRIDO[3,4-. B]INDOLE-. 1,4-. DIONE ...
... cyclic-GMP phosphodiesterase activity IBA Inferred from Biological aspect of Ancestor. more info ... cyclic nucleotide phosphodiesterase. cGMP-specific phosphodiesterase PDE5A2. cGMP-specific phosphodiesterase type 5A. ... This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. ... cyclic-GMP phosphodiesterase activity IDA Inferred from Direct Assay. more info ...
gmp binding. cgmp binding. cyclic-nucleotide phosphodiesterase activity. 3,5-cyclic-nucleotide phosphodiesterase activity. ... cyclic phosphodiesterase subunit gamma (HMDBP00561). IdentificationBiological propertiesGene propertiesProtein properties ... cyclic-nucleotide phosphodiesterase activity. Specific Function. Participates in processes of transmission and amplification of ... Piri N, Gao YQ, Danciger M, Mendoza E, Fishman GA, Farber DB: A substitution of G to C in the cone cGMP-phosphodiesterase gamma ...
Cyclic GMP-Hydrolyzing Phosphodiesterases Sharron H. Francis, Jackie D. Corbin, Erwin Bischoff ... This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this ... 3.Bayer Schering Pharma AG Cardiology ResearchPharma Research CenterWuppertalGermany ...
Phosphodiesterase 6B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... Belongs to the cyclic nucleotide phosphodiesterase family.. Family:. * Belongs to the cyclic nucleotide phosphodiesterase ... GMP-PDE Beta 3 4 * EC 3.1.4.35 4 58 * PDEB 3 4 ... PDE6B (Phosphodiesterase 6B) is a Protein Coding gene. Diseases ... A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family. (PMID: ...
... cyclic-AMP and -GMP phosphodiesterase 11A. *EC 3.1.4. *EC 3.1.4.17 ... Lane 2: Human cell line RT-4. Lane 3: Human cell line U-251MG sp ... cAMP and cGMP cyclic nucleotide phosphodiesterase 11A. *cAMP ...
... cyclic-AMP and -GMP phosphodiesterase 11A is an enzyme that in humans is encoded by the PDE11A gene. The 3,5-cyclic ... Yuasa K, Ohgaru T, Asahina M, Omori K (2001). "Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A): ... Beavo JA, Conti M, Heaslip RJ (1994). "Multiple cyclic nucleotide phosphodiesterases". Mol. Pharmacol. 46 (3): 399-405. PMID ... cyclic nucleotide phosphodiesterase 11A: localization in human tissues". Int. J. Impot. Res. 17 (4): 320-5. doi:10.1038/sj.ijir ...
... namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKI alpha, cGKI ... less thanbrgreater than less thanbrgreater thanThe findings give hints that the cyclic GMP- and cyclic AMP-dependent signal ... Cyclic GMP/cyclic AMP signaling, Immunohistochemistry National Category Engineering and Technology Identifiers. URN: urn:nbn:se ... immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKI alpha, and cGKI, as well as with the cyclic ...
In addition, a clear therapeutic effect was present in mice treated at 2 weeks of age as well as in mice treated at 3 months of ... In addition, a clear therapeutic effect was present in mice treated at 2 weeks of age as well as in mice treated at 3 months of ... Specifically, we compare the influence of two different AAV vector capsids, AAV2/5 (Y719F) and AAV2/8 (Y733F), on restoration ... Specifically, we compare the influence of two different AAV vector capsids, AAV2/5 (Y719F) and AAV2/8 (Y733F), on restoration ...
1975). "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic ... The PDE2 (phosphodiesterase 2) enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs ... cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism" (PDF). Gen Physiol Biophys. 22 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488-520. doi:10.1124/pr. ...
... cyclic-GMP phosphodiesterase activity *[MF] calmodulin-dependent cyclic-nucleotide phosphodiesterase activity *[MF] hydrolase ... cyclic-AMP phosphodiesterase activity *[MF] cGMP binding *[MF] calcium- and calmodulin-regulated 3,5- ...
Design and synthesis of xanthines and cyclic GMP analogs as potent inhibitors of PDE5. Phosphodiesterase Inhibitors (1996), 135 ... Cyclic GMP. Description. Guanosine cyclic 3,5-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which ... cyclic nucleotide phosphodiesterase 1A. General function:. Involved in catalytic activity. Specific function:. Cyclic ... cyclic nucleotide phosphodiesterase 1B. General function:. Involved in catalytic activity. Specific function:. Cyclic ...
... which activates a cyclic GMP phosphodiesterase. The question arises as to whether the hydrolysis of cyclic GMP that results ... CYCLIC-GMP CASCADE OF VISION ANNUAL REVIEW OF NEUROSCIENCE Stryer, L. 1986; 9: 87-119 Abstract. Cyclic GMP is central to visual ... cyclic monophosphorothioate was hydrolyzed by cyclic GMP phosphodiesterase in H2(18)O to give [16O,18O]guanosine 5- ... TRANSDUCIN AND THE CYCLIC-GMP PHOSPHODIESTERASE OF RETINAL ROD OUTER SEGMENTS METHODS IN ENZYMOLOGY Stryer, L., Hurley, J. B., ...
... whereas the c-di-GMP phosphodiesterases (PDEs) contain an EAL domain or an HD-GYP domain and hydrolyze c-di-GMP into linear ... cyclic diguanosine monophosphate (c-di-GMP) plays multiple key roles in bacterial physiology and virulence (10-12). c-di-GMP ... Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev 77:1-52. doi:10.1128/MMBR. ... Cyclic Di-GMP Riboswitch-Regulated Type IV Pili Contribute to Aggregation of Clostridium difficile. Eric Bordeleau, Erin B. ...
... cyclic GMP: step 1/1.. * Sequence similarities. Belongs to the cyclic nucleotide phosphodiesterase family.. Contains 2 GAF ... cGMP binding cGMP specific 35 cyclic nucleotide phosphodiesterase antibody. *cGMP binding cGMP specific phosphodiesterase ... Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase ... See all 5 Publications for this product Publishing research using ab14672? Please let us know so that we can cite the reference ...
... yielding linear dimeric GMP (l-di-GMP). This activity was designated PDE-A. The subsequent hydrolysis of l-di-GMP into two GMP ... Its involvement in hydrolysis of the novel second messenger cyclic dimeric GMP (c-di-GMP) was demonstrated in vivo but not in ... Treatment of l-di-GMP with mung bean nuclease resulted in GMP, as judged by its comigration with chemically synthesized GMP. To ... and found to function as a c-di-GMP-specific phosphodiesterase, not as a cAMP-specific phosphodiesterase, in contrast to ...
... cyclic GMP: step 1/1.. * Sequence similarities. Belongs to the cyclic nucleotide phosphodiesterase family.. Contains 2 GAF ... cGMP binding cGMP specific 35 cyclic nucleotide phosphodiesterase antibody. *cGMP binding cGMP specific phosphodiesterase ... Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase ... cGMP binding cGMP specific 3 5 cyclic nucleotide phosphodiesterase antibody. * ...
GMP-PDE beta; rod cGMP-phosphodiesterase beta-subunit; CSNBAD2;. ... Antigen standard for phosphodiesterase 6B, cGMP-specific, rod, ... PDE6B; phosphodiesterase 6B, cGMP-specific, rod, beta; PDEB; rod cGMP-specific 3,5-cyclic phosphodiesterase subunit beta; ... This product includes 3 vials: 1 vial of gene-specific cell lysate, 1 vial of control vector cell lysate, and 1 vial of loading ... Each lysate vial contains 0.1 mg lysate in 0.1 ml (1 mg/ml) of RIPA Buffer (50 mM Tris-HCl pH7.5, 250 mM NaCl, 5 mM EDTA, 50 mM ...
Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods. Kawamura, S., Murakami, M. ... Injection of GTP-binding protein or cyclic GMP phosphodiesterase hyperpolarizes retinal rods. Clack, J.W., Oakley, B., Stein, P ... Cyclic GMP can increase rod outer-segment light-sensitive current 10-fold without delay of excitation. Cobbs, W.H., Pugh, E.N. ... Cyclic GMP injected into retinal rod outer segments increases latency and amplitude of response to illumination. Nicol, G.D., ...
  • less thanbrgreater than less thanbrgreater thanThe present study aimed to investigate by means of immunohistochemistry in the human prostate the expression and distribution of key mediators of the NO pathway, namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKI alpha, cGKI), in relation to PDE5, protein kinase A (cAK), and the vasoactive intestinal polypeptide (VIP). (diva-portal.org)
  • 6 Like NO, cGMP can affect multiple signaling pathways ( Figure 1 A). 1,5,6 To date, three classes of cGMP receptor proteins have been identified: cyclic nucleotide-gated (CNG) cation channels, cGMP-regulated PDEs, which hydrolyze cAMP and/or cGMP, and cGMP-dependent protein kinases (cGKs). (ahajournals.org)
  • cAMP coordinates the regulation of these cellular responses by activating cAMP-dependent protein kinases (PKAs) ( 4 ), specific guanine nucleotide exchange factors (EPACs) ( 5 ), and cyclic nucleotide-gated ion channels ( 6 ). (pnas.org)
  • Effect of cyclic GMP-increasing agents nitric oxide and C-type natriuretic peptide on bovine chromaffin cell function: inhibitory role mediated by cyclic GMP-dependent protein kinase. (aspetjournals.org)
  • In the present study, we apply nano-filtration technology to mimic splenic retention and demonstrate that deformability of transmissible mature stage V gametocytes is regulated by parasite cyclic AMP-dependent kinase signalling. (prolekare.cz)
  • Ivins Zito C, Kontaridis MI, Fornaro M, Feng GS, Bennett AM. SHP-2 regulates the phosphatidylinositide 3'-kinase/Akt pathway and suppresses caspase 3-mediated apoptosis. (harvard.edu)
  • Connecting quorum sensing, c-di-GMP, pel polysaccharide, and biofilm formation in Pseudomonas aeruginosa through tyrosine phosphatase TpbA (PA3885). (pseudomonas.com)
  • Importantly, an optimal concentration of 4,5-dihydroxy-2,3-pentanedione (DPD) was critical for maximal biofilm development. (asmscience.org)
  • The steps of biofilm formation, as described in this article are (1) reversible attachment, likely via the flagellar pole, (2) irreversible attachment via the long axis of the cell, resulting in a monolayer of cells, (3) microcolony formation, (4) macrocolony formation, and (5) dispersion. (asmscience.org)
  • c‐di‐GMP nearly ubiquitously downregulates bacterial motility and stimulates biofilm formation, that is, the synthesis of bacterial adhesins and extracellular matrix components. (embopress.org)
  • Also, virulence genes involved in acute infections by some pathogenic bacteria are downregulated by c‐di‐GMP, while chronic infections are often associated with high c‐di‐GMP levels and biofilm formation ( Tamayo et al , 2007 ). (embopress.org)
  • Phenotypic studies revealed that ml1419c expression altered colony morphology, motility and biofilm formation of P. aeruginosa PAO1 in a manner consistent with increased cyclic di-GMP production. (microbiologyresearch.org)
  • He is a member of a number of scientific and professional societies, including the American Society for Pharmacology and Experimental Therapeutics and the Society for Neuroscience, is a Fellow of the American College of Neuropsychopharmacology, and chaired the Gordon Research Conference on Cyclic Nucleotide Phosphodiesterases. (buffalo.edu)
  • Thus, this protein was renamed DgcA (Diguanylate cyclase A). These results also demonstrated the ability to use P. aeruginosa as a heterologous host for characterizing the function of proteins involved in the cyclic di-GMP pathway of a pathogen refractory to in vitro growth, M. leprae . (microbiologyresearch.org)
  • The guanylyl cyclase (GC) activator, NOR-3, and cGMP PDE inhibitors, trequinsin and MY5445, displayed similar growth-inhibitory activity as SS, but the adenylyl cyclase activator, forskolin, and other PDE inhibitors had no effect. (aacrjournals.org)
  • Phosphodiesterase type 5A (PDE5A) inhibitors acutely suppress beta-adrenergic receptor (β-AR) stimulation in left ventricular myocytes and hearts. (springer.com)
  • GENTAUR antibody-antibodies.com The Marketplace for Antibodies : Microbial cyclic β-(1→3),(1→6)-glucans as potential drug carriers: Interaction studies between cyclic β-glucans isolated from Bradyrhizobium japonicum and betulinic acid. (antibody-antibodies.com)
  • A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. (hmdb.ca)
  • Phosphodiesterase type 5 in men with vasculogenic and post-radical prostatectomy erectile dysfunction: is there a molecular difference? (nih.gov)
  • Type 5 phosphodiesterase regulates glioblastoma multiforme aggressiveness and clinical outcome. (nih.gov)
  • In this work, we investigated the role of the primary type IV pilus (T4P) locus in c-di-GMP-dependent cell aggregation. (asm.org)
  • Due to its linear conformation, 5'-pApA is intended to serve as a negative control for c-di-AMP in type I IFN induction assays. (invivogen.com)
  • Engineered Biosynthesis of 5/5/6 Type Polycyclic Tetramate Macrolactams in an Ikarugamycin (5/6/5 Type)-Producing Chassis. (bioportfolio.com)
  • X-ray crystal structure of pactamide G () sets an example for resolving the absolute configuration of 5/5/6 type PoTeMs. (bioportfolio.com)
  • SS did not induce apoptosis of normal human mammary epithelial cells (HMEC) nor did it inhibit phosphodiesterase (PDE) activity in HMEC lysates. (aacrjournals.org)
  • 5 These studies also uncovered a marked complexity of signaling via NO/NPs, for example that NO can both inhibit and promote atherogenesis. (ahajournals.org)
  • caffeine and theophylline inhibit cAMP phosphodiesterase, which degrades cAMP - thus enabling higher levels of cAMP than would otherwise be had. (wikipedia.org)
  • uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. (diva-portal.org)
  • Amino acids critical for the activity of the parent cyclic peptide were uncovered using alanine-scanning, and a series of non-natural analogues synthesized and assessed. (bioportfolio.com)
  • Vascular smooth muscle responses to cGMP-dependent vasodilatory stimuli are regulated by the activity of vascular smooth muscle phosphodiesterase, which catalyzes hydrolyzation of cGMP to inactive products (9) . (onlinejacc.org)
  • 3. Hackett G, Dean J, Kell P, Price D, Ralph D, Speakman M, Wylie K. British Society for Sexual Medicine in: Guidelines on the Management of Erectile Dysfunction. (cogprints.org)
  • 5. Vinik A, Richardson D. Erectile Dysfunction in Diabetes: Pills for Penile Failure J. Clin. (cogprints.org)