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)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.Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.Purinones3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.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.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.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.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.Nucleotides, CyclicAtrial 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.Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESOxadiazolesCyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.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.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.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.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.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.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.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.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.Arginine: An essential amino acid that is physiologically active in the L-form.Quinoxalines8-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.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)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.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.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.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.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Kinetics: The rate dynamics in chemical or physical systems.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.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.Aminoquinolines: Quinolines substituted in any position by one or more amino groups.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).Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.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.omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.S-Nitrosoglutathione: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.Rolipram: A phosphodiesterase 4 inhibitor with antidepressant properties.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.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)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.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.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.Organic Chemistry Phenomena: The conformation, properties, reaction processes, and the properties of the reactions of carbon compounds.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.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.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.Aorta: The main trunk of the systemic arteries.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.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.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.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.Light: That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.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.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.Guanine NucleotidesInosine 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.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.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)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.-.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.-.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)Phosphodiesterase 5 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 5.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Vinca Alkaloids: A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.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.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.Ambystoma: A genus of the Ambystomatidae family. The best known species are the axolotl AMBYSTOMA MEXICANUM and the closely related tiger salamander Ambystoma tigrinum. They may retain gills and remain aquatic without developing all of the adult characteristics. However, under proper changes in the environment they metamorphose.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Ferricyanides: Inorganic salts of the hypothetical acid, H3Fe(CN)6.Malpighian Tubules: Slender tubular or hairlike excretory structures found in insects. They emerge from the alimentary canal between the mesenteron (midgut) and the proctodeum (hindgut).Enzyme Activators: Compounds or factors that act on a specific enzyme to increase its activity.Rhodopsin: A purplish-red, light-sensitive pigment found in RETINAL ROD CELLS of most vertebrates. It is a complex consisting of a molecule of ROD OPSIN and a molecule of 11-cis retinal (RETINALDEHYDE). Rhodopsin exhibits peak absorption wavelength at about 500 nm.Xanthines: Purine bases found in body tissues and fluids and in some plants.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.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.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.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Darkness: The absence of light.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Retinal Rod Photoreceptor Cells: Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination.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.Cyclic CMP: A cyclic nucleotide formed from CYTIDINE TRIPHOSPHATE by the action of cytidylate cyclase. It is a potential cyclic nucleotide intracellular mediator of signal transductions.

Relaxin is a potent renal vasodilator in conscious rats. (1/5723)

The kidneys and other nonreproductive organs vasodilate during early gestation; however, the "pregnancy hormones" responsible for the profound vasodilation of the renal circulation during pregnancy are unknown. We hypothesized that the ovarian hormone relaxin (RLX) contributes. Therefore, we tested whether the administration of RLX elicits renal vasodilation and hyperfiltration in conscious adult, intact female rats. After several days of treatment with either purified porcine RLX or recombinant human RLX 2 (rhRLX), effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) increased by 20%-40%. Comparable renal vasodilation and hyperfiltration was also observed in ovariectomized rats, suggesting that estrogen and progesterone are unnecessary for the renal response to rhRLX. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester completely abrogated the increase in ERPF and GFR elicited by chronic administration of purified porcine RLX. In contrast, the renal vasoconstrictory response to angiotensin II was attenuated by the RLX treatment. Short-term infusion of purified porcine RLX to conscious rats over several hours failed to increase ERPF and GFR. Plasma osmolality was consistently reduced by the chronic administration of both RLX preparations. In conclusion, the renal and osmoregulatory effects of chronic RLX administration to conscious rats resemble the physiological changes of pregnancy in several respects: (a) marked increases in ERPF and GFR with a mediatory role for nitric oxide; (b) attenuation of the renal circulatory response to angiotensin II; and (c) reduction in plasma osmolality.  (+info)

Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat. (2/5723)

We previously reported that adrenomedullin (AM), a potent vasodilator peptide discovered in pheochromocytoma cells, stimulates nitric oxide (NO) release in the rat kidney. To further investigate whether the NO-cGMP pathway is involved in the mechanisms of AM-induced vasodilation, we examined the effects of E-4021, a cGMP-specific phosphodiesterase inhibitor, on AM-induced vasorelaxation in aortic rings and perfused kidneys isolated from Wistar rats. We also measured NO release from the kidneys using a chemiluminescence assay. AM (10(-10) to 10(-7) mol/L) relaxed the aorta precontracted with phenylephrine in a dose-dependent manner. Denudation of endothelium (E) attenuated the vasodilatory action of AM (10(-7) mol/L AM: intact (E+) -25.7+/-5.2% versus denuded (E-) -7. 8+/-0.6%, P<0.05). On the other hand, pretreatment with 10(-8) mol/L E-4021 augmented AM-induced vasorelaxation in the intact aorta (-49. 0+/-7.9%, P<0.05) but not in the denuded one. E-4021 also enhanced acetylcholine (ACh)-induced vasorelaxation in the rat intact aorta (10(-7) mol/L ACh -36.6+/-8.4% versus 10(-8) mol/L E-4021+10(-7) mol/L ACh -62.7+/-3.1%, P<0.05). In perfused kidneys, AM-induced vasorelaxation was also augmented by preincubation with E-4021 (10(-9) mol/L AM -15.4+/-0.6% versus 10(-8) mol/L E-4021+10(-9) mol/L AM -23.6+/-1.2%, P<0.01). AM significantly increased NO release from rat kidneys (DeltaNO: +11.3+/-0.8 fmol. min-1. g-1 kidney at 10(-9) mol/L AM), which was not affected by E-4021. E-4021 enhanced ACh-induced vasorelaxation (10(-9) mol/L ACh -9.7+/-1.7% versus 10(-8) mol/L E-4021+10(-9) mol/L ACh -18.8+/-2.9%, P<0.01) but did not affect ACh-induced NO release from the kidneys. In the aorta and the kidney, 10(-4) mol/L of NG-nitro-L-arginine methyl ester, an NO synthase inhibitor, and 10(-5) mol/L of methylene blue, a guanylate cyclase inhibitor, reduced the vasodilatory effect of AM. These results suggest that the NO-cGMP pathway is involved in the mechanism of AM-induced vasorelaxation, at least in the rat aorta and kidney.  (+info)

Nitric oxide modulates endothelin 1-induced Ca2+ mobilization and cytoskeletal F-actin filaments in human cerebromicrovascular endothelial cells. (3/5723)

A functional interrelation between nitric oxide (NO), the endothelial-derived vasodilating factor, and endothelin 1 (ET-1), the potent vasoconstrictive peptide, was investigated in microvascular endothelium of human brain. Nor-1 dose-dependently decreased the ET-1-stimulated mobilization of Ca2+. This response was mimicked with cGMP and abrogated by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase G. These findings indicate that NO and ET-1 interactions involved in modulation of intracellular Ca2+ are mediated by cGMP/protein kinase G. In addition, Nor-1-mediated effects were associated with rearrangements of cytoskeleton F-actin filaments. The results suggest mechanisms by which NO-ET-1 interactions may contribute to regulation of microvascular function.  (+info)

Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3',5'-cyclic diguanylic acid. (4/5723)

The effect of the novel, naturally occurring nucleotide cyclic diguanylic acid (c-di-GMP) on the lymphoblastoid CD4+ Jurkat cell line was studied. When exposed to 50 microM c-di-GMP, Jurkat cells exhibited a markedly elevated expression of the CD4 receptor of up to 6.3-fold over controls. C-di-GMP also causes blockage of the cell cycle at the S-phase, characterized by increased cellular thymidine uptake, reduction in G2/M-phase cells, increase in S-phase cells and decreased cell division. Additionally c-di-GMP naturally enters these cells and binds irreversibly to the P21ras protein. The effects described appear to be unique for c-di-GMP.  (+info)

Enantioselective inhibition of the biotransformation and pharmacological actions of isoidide dinitrate by diphenyleneiodonium sulphate. (5/5723)

1. We have shown previously that the D- and L- enantiomers of isoidide dinitrate (D-IIDN and L-IIDN) exhibit a potency difference for relaxation and cyclic GMP accumulation in isolated rat aorta and that this is related to preferential biotransformation of the more potent enantiomer (D-IIDN). The objective of the current study was to examine the effect of the flavoprotein inhibitor, diphenyleneiodonium sulphate (DPI), on the enantioselectivity of IIDN action. 2. In isolated rat aortic strip preparations, exposure to 0.3 microM DPI resulted in a 3.6 fold increase in the EC50 value for D-IIDN-induced relaxation, but had no effect on L-IIDN-induced relaxation. 3. Incubation of aortic strips with 2 microM D- or L-IIDN for 5 min resulted in significantly more D-isoidide mononitrate formed (5.0 +/- 1.5 pmol mg protein(-1)) than L-isoidide mononitrate (2.1 +/- 0.7 pmol mg protein(-1)) and this difference was abolished by pretreatment of tissues with 0.3 microM DPI. DPI had no effect on glutathione S-transferase (GST) activity or GSH-dependent biotransformation of D- or L-IIDN in the 105,000 x g supernatant fraction of rat aorta. 4. Consistent with both the relaxation and biotransformation data, treatment of tissues with 0.3 microM DPI significantly inhibited D-IIDN-induced cyclic GMP accumulation, but had no effect on L-IIDN-induced cyclic GMP accumulation. 5. In the intact animal, 2 mg kg(-1) DPI significantly inhibited the pharmacokinetic and haemodynamic properties of D-IIDN, but had no effect L-IIDN. 6. These data suggest that the basis for the potency difference for relaxation by the two enantiomers is preferential biotransformation of D-IIDN to NO, by an enzyme that is inhibited by DPI. Given that DPI binds to and inhibits NADPH-cytochrome P450 reductase, the data are consistent with a role for the cytochromes P450-NADPH-cytochrome P450 reductase system in this enantioselective biotransformation process.  (+info)

Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxan-induced hyperglycaemia. (6/5723)

1. We examined whether endogenous inhibitors of NO synthesis are involved in the augmentation of intimal hyperplasia in rabbits with hyperglycaemia induced by alloxan. 2. Four weeks after the endothelial denudation of carotid artery which had been performed 12 weeks after alloxan, the intimal hyperplasia was greatly augmented with hyperglycaemia. The degree of hyperplasia was assessed using three different parameters of histopathological findings as well as changes in luminal area and intima: media ratio. 3. There were positive and significant correlations between intima:media ratio, plasma glucose, and concentrations of N(G)-monomethyl-L-arginine (L-NMMA) and N(G), N(G)-dimethyl-L-arginine (ADMA) in endothelial cells, that is, the intima:media ratio became greater as plasma glucose and endothelial L-NMMA and ADMA were increased. Furthermore, endothelial L-NMMA and ADMA were increased in proportion to the increase in plasma glucose. 4. In contrast, there were inverse and significant correlations between cyclic GMP production by carotid artery strips with endothelium and plasma glucose, between cyclic GMP production and endothelial L-NMMA and ADMA, and between the intima:media ratio and cyclic GMP production. 5. Exogenously applied L-NMMA and ADMA inhibited cyclic GMP production in a concentration-dependent manner. IC50 values were determined to be 12.1 microM for the former and 26.2 microM for the latter. The cyclic GMP production was abolished after the deliberate removal of endothelium from the artery strips. 6. These results suggest that the augmentation of intimal hyperplasia with hyperglycaemia is closely related to increased accumulation of L-NMMA and ADMA with hyperglycaemia, which would result in an accelerated reduction in NO production/release by endothelial cells.  (+info)

Growth-inhibitory effect of cyclic GMP- and cyclic AMP-dependent vasodilators on rat vascular smooth muscle cells: effect on cell cycle and cyclin expression. (7/5723)

1. The possibility that the antiproliferative effect of cyclic GMP- and cyclic AMP-dependent vasodilators involves an impaired progression of vascular smooth muscle cells (VSMC) through the cell cycle and expression of cyclins, which in association with the cyclin-dependent kinases control the transition between the distinct phases of the cell cycle, was examined. 2. FCS (10%) stimulated the transition of quiescent VSMC from the G0/G1 to the S phase (maximum within 18-24 h and then to the G2/M phase (maximum within 22-28 h). Sodium nitroprusside and 8-Br-cyclic GMP, as well as forskolin and 8-Br-cyclic AMP markedly reduced the percentage of cells in the S phase after FCS stimulation. 3. FCS stimulated the low basal protein expression of cyclin D1 (maximum within 8-24 h) and E (maximum within 8-38 h) and of cyclin A (maximum within 14-30 h). The stimulatory effect of FCS on cyclin D1 and A expression was inhibited, but that of cyclin E was only minimally affected by the vasodilators. 4. FCS increased the low basal level of cyclin D1 mRNA after a lag phase of 2 h and that of cyclin A after 12 h. The vasodilators significantly reduced the FCS-stimulated expression of cyclin D1 and A mRNA. 5. These findings indicate that cyclic GMP- and cyclic AMP-dependent vasodilators inhibit the proliferation of VSMC by preventing the progression of the cell cycle from the G0/G1 into the S phase, an effect which can be attributed to the impaired expression of cyclin D1 and A.  (+info)

Nonanticoagulant heparin prevents coronary endothelial dysfunction after brief ischemia-reperfusion injury in the dog. (8/5723)

BACKGROUND: Coronary endothelial dysfunction after brief ischemia-reperfusion (IR) remains a clinical problem. We investigated the role of heparin and N-acetylheparin, a nonanticoagulant heparin derivative, in modulating coronary endothelial function after IR injury, with an emphasis on defining the role of the nitric oxide (NO)-cGMP pathway in the heparin-mediated effect. METHODS AND RESULTS: Male mongrel dogs were surgically instrumented, and the effects of both bovine heparin and N-acetylheparin on coronary endothelial vasomotor function, expressed as percent change from baseline flow after acetylcholine challenge, were studied after 15 minutes of regional ischemia of the left anterior descending artery (LAD) followed by 120 minutes of reperfusion. In dogs treated with placebo (saline), coronary vasomotor function was significantly (P+info)

*GUCY1B3

"Guanylyl cyclases and signaling by cyclic GMP". Pharmacol. Rev. 52 (3): 375-414. PMID 10977868. Chhajlani V, Frändberg PA, ...

*Diguanylate cyclase

... 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 ... D'Argenio, D.A.; Miller, S.I. (2004). "Cyclic di-GMP as a bacterial second messenger". Microbiology. 150 (Pt 8): 2497-502. doi: ... Jenal, U.; Jacob Malone (2006). "Mechanisms of Cyclic-di-GMP Signaling in Bacteria". Review. 40: 385-407. doi:10.1146/annurev. ...

*King-Wai Yau

Yau KW, Baylor DA (1989). "Cyclic GMP-activated conductance of retinal photoreceptor cells". Annual Review of Neuroscience. 12 ... "Cyclic GMP-activated conductance of retinal photoreceptor cells", 590 citations 1990 "Primary structure and functional ... Dhallan RS, Yau KW, Schrader KA, Reed RR (1990). "Primary structure and functional expression of a cyclic nucleotide-activated ... expression of a cyclic nucleotide-activated channel from olfactory neurons", 672 citations 1998 "Identification of ligands for ...

*Cinaciguat

This increases biosynthesis of cyclic GMP, resulting in vasodilation. Riociguat, another drug stimulating sGC, but with a ... reducing cyclic GMP degradation. Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2009. ...

*CGAS-STING cytosolic DNA sensing pathway

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 ... 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 ... "Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses". Science 23 August 2013: Vol. 341 no. 6148 pp ...

*Riboswitch

Two classes of cyclic di-GMP riboswitches are known: cyclic di-GMP-I riboswitches and cyclic di-GMP-II riboswitches. These ... cyclic AMP-GMP riboswitches bind the signaling molecule cyclic AMP-GMP. These riboswitches are structurally related to cyclic ... "cyclic di-GMP" below). cyclic di-AMP riboswitches (also called ydaO/yuaA) bind the signaling molecule cyclic di-AMP. cyclic di- ... GMP riboswitches bind the signaling molecule cyclic di-GMP in order to regulate a variety of genes controlled by this second ...

*Pseudomonas aeruginosa

Cyclic di-GMP is a major contributor to biofilm adherent properties. This signalling molecule in high quantities makes ... Additionally, genes involved in cyclic-di-GMP signaling may contribute to resistance. When grown in vitro conditions designed ... PSL stimulates cdi-GMP production, while high cd-GMP turns on the operon and increases activity of the operon. Recent studies ... Abu EA, Su S, Sallans L, Boissy RE, Greatens A, Heineman WR, Hassett DJ (August 2013). "Cyclic voltammetric, fluorescence and ...

*Biological functions of hydrogen sulfide

"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... cyclic guanosine monophosphate (cGMP). In H2S therapy immediately following an AMI, increased cGMP triggers an increase in ...

*Gaseous signaling molecules

... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... doi:10.1161/01.ATV0000110785.96039.f6 (inactive 2017-08-15). Boerth NJ, Dey NB, Cornwell TL, Lincoln TM (1997). "Cyclic GMP- ... cyclic guanosine monophosphate (cGMP). In H2S therapy immediately following an AMI, increased cGMP triggers an increase in ...

*Nicorandil

Vrolix, M; Raeymaekers, L; Wuytack, F; Hofmann, F; Casteels, R (Nov 1, 1988). "Cyclic GMP-dependent protein kinase stimulates ... Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), ... "Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ...

*Stimulator of interferon genes

... cyclic GMP-AMP, or cGAMP). After cyclic GMP-AMP bound STING is activated, it enhances TBK1's activity to phosphorylate IRF3 and ... Shu C, Yi G, Watts T, Kao CC, Li P (Jul 2012). "Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic ... Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ (Feb 2013). "Cyclic GMP-AMP is an endogenous second messenger in innate ... Sun L, Wu J, Du F, Chen X, Chen ZJ (Feb 2013). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I ...

*PPP1R17

A Purkinje cell substrate of the cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 274 (6): 3485-95. ...

*PDE6B

"Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina". Journal of Cyclic Nucleotide ... Anant JS, Ong OC, Xie HY, Clarke S, O'Brien PJ, Fung BK (Jan 1992). "In vivo differential prenylation of retinal cyclic GMP ... Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase]". Bioorganicheskaia Khimiia ... Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded ...

*Retrograde signaling

Lei, S; Jackson, MF; Jia, Z; Roder, J; Bai, D; Orser, BA; MacDonald, JF (Jun 2000). "Cyclic GMP-dependent feedback inhibition ...

*Shewanella woodyi

"Nitric Oxide Regulation of Cyclic di-GMP Synthesis and Hydrolysis inShewanella woodyi". Biochemistry. 51 (10): 2087-2099. doi: ...

*Antimicrobial peptides

Cyclic-di-GMP signaling had also been involved in the regulation of antimicrobial peptide resistance in Pseudomonas aeruginosa ... Chua SL, Tolker-Nielsen T, Kjelleberg S, Givskov M, Yang L (2013). "Bis-(3′-5′)-cyclic dimeric GMP regulates antimicrobial ... oral cyclic peptide Telavancin, bacterial infection, IV Vancomycin, bacterial infection, IV. Some of the cecropins (e.g. ... cyclic peptide) Dalbavancin, bacterial infections, IV Daptomycin, bacterial infections, IV Enfuvirtide, HIV, subcutaneous ...

*Systems medicine

"Clinical relevance of cyclic GMP modulators: A translational success story of network pharmacology". Clinical Pharmacology & ...

*Calcium in biology

Pugh Jr, E. N.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate ...

*PilZ domain

C-di-GMP, cyclic diguanosine monophosphate, the second messenger in cells, is widespread in and unique to the bacterial kingdom ... c-di-GMP complex from Vibrio cholerae shows c-di-GMP contacting seven of nine strongly conserved residues. Binding of c-di-GMP ... Wolfe, AJ; Visick, KL (Jan 2008). "Get the message out: cyclic-Di-GMP regulates multiple levels of flagellum-based motility". ... PilZ is a c-di-GMP binding domain and PilZ domain-containing proteins represent the best studied class of c-di-GMP effectors. ...

*Riociguat

... reducing cyclic GMP degradation. Endothelin receptor antagonist, another class of drugs used in PAH "Background Riociguat". ... NO binds to soluble guanylate cyclase (sGC) and mediates the synthesis of the secondary messenger cyclic guanosine ...

*Adaptation (eye)

Pugh Jr, E. N.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate ... Sensitivity to light is modulated by changes in intracellular calcium ions and cyclic guanosine monophosphate. The sensitivity ...

*Sodium azide

... increases cyclic GMP levels in brain and liver by activation of guanylate cyclase. Stevens E. D.; Hope H. (1977 ... Kimura, Hiroshi; Mittal, Chandra K.; Murad, Ferid (1975-10-23). "Increases in cyclic GMP levels in brain and liver with sodium ...

*Second messenger system

Examples of second messenger molecules include cyclic AMP, cyclic GMP, inositol trisphosphate, diacylglycerol, and calcium. The ... He found that epinephrine had to trigger a second messenger, cyclic AMP, for the liver to convert glycogen to glucose. The ... Secondary messenger systems can be synthesized and activated by enzymes, for example, the cyclases that synthesize cyclic ... important feature of the second messenger signaling system is that second messengers may be coupled downstream to multi-cyclic ...

*PRKG1

Komalavilas P, Lincoln TM (Mar 1994). "Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic GMP-dependent ... "Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10". Cytogenetics and Cell ...

*ITPR1

Komalavilas P, Lincoln TM (Mar 1994). "Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic GMP-dependent ...

*Vasodilator-stimulated phosphoprotein

Lawrence DW, Pryzwansky KB (2001). "The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein ... VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. Vasodilator-stimulated phosphoprotein has been shown ... Halbrügge M, Eigenthaler M, Polke C, Walter U (1992). "Protein phosphorylation regulated by cyclic nucleotide-dependent protein ...

*Photoreceptor cell

Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound ... The net concentration of intracellular cGMP is reduced (due to its conversion to 5' GMP via PDE), resulting in the closure of ... PDE then catalyzes the hydrolysis of cGMP to 5' GMP. This is the second amplification step, where a single PDE hydrolyses about ... In the dark, cells have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which opens ion ...

*Netrin

"Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning". Nature. 423 (6943): 990-5 ...
Bis-(3-5)-cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger that regulates multiple cellular behaviors in most major bacterial phyla. C-di-GMP signaling in bacterial often includes enzymes that are responsible for the synthesis and degradation of c-di-GMP, effector proteins or molecules that bind c-di-GMP, and targets that interact with effectors. However, little is known about the specificity of c-di-GMP signaling in controlling virulence and bacterial behaviors. In this work, we have investigated the c-di-GMP signaling network using the model plant pathogen Dickeya dadantii 3937. In Chapter 2, we characterized two PilZ domain proteins that regulate biofilm formation, swimming motility, Type III secretion system (T3SS) gene expression, and pectate lyase production in high c-di-GMP level conditions. YcgR3937 binds c-di-GMP both in vivo and in vitro. Next, we revealed a sophisticated regulatory network that connects the sRNA, c-di-GMP signaling, and flagellar master
Cells of the murine neuroblastoma clone N1E-115 possess muscarinic receptors that influence the intracellular level of cyclic nucleotides. The stimulation of [3H]cyclic GMP levels occurs only with intact cells and has an EC50 near the "low-affinity" agonist equilibrium dissociation constant (KL) determined by radioligand binding assays. The inhibition of prostaglandin E1-stimulated [3H]cyclic AMP formation has an EC50 close to the value for the "high-affinity" agonist equilibrium dissociation constant (KH). During sequential subculturing in medium supplemented with newborn bovine serum, the inhibition of [3H]cyclic AMP was maintained, but the [3H]cyclic GMP response declined dramatically, and after 7 subculturings it was essentially absent. The time course for [3H]cyclic GMP formation in a late subculture with an 88% loss of the response was identical with the time course in early subcultures. A normal [3H]cyclic GMP response to bradykinin and histamine was demonstrated to be present in cells ...
TY - JOUR. T1 - Determination?of?association?constants?between?5?-guanosine?monophosphate?gel?and?aromatic?compounds?by?capillary?electrophoresis. AU - Kaneta, Takashi. PY - 2013. Y1 - 2013. M3 - Article. C2 - 23522259. VL - 1288. SP - 149. EP - 154. JO - Journal?of?Chromatography?A. JF - Journal?of?Chromatography?A. ER - ...
cGMP Dependent Kinase Inhibitor Peptide chemical properties, What are the chemical properties of cGMP Dependent Kinase Inhibitor Peptide 82801-73-8, What are the physical properties of cGMP Dependent Kinase Inhibitor Peptide ect.
In animal models of MI, gene expression of ANF is reportedly upregulated23 and correlates strongly with diastolic wall stress and stretch.24,25 Our present results on myocardial ANF mRNA content showed a marked increase in this factor in isoproterenol- and cinaciguat plus isoproterenol-treated rats, suggesting end-diastolic wall stress. Recent studies also showed that production of cGMP by activation of natriuretic peptides receptor just before therapeutic reperfusion has a significant anti-infarct effect in both animals26 and humans.27 Our results also showed a correlation between increased myocardial ANF mRNA expression and plasma cGMP levels in these groups of rats, which could be a phenomenon that opposes MI. In heart failure, increased cGMP concentrations in extracellular fluids, including plasma28 and urine,29 are believed to result from its passage through the cellular membrane30 as plasma cGMP is seen as an overspill of intracellular cGMP. However, plasma cGMP levels do not necessarily ...
TY - JOUR. T1 - YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway. AU - Hsu, Hun Kung. AU - Juan, Shu Hui. AU - Ho, Pei Yin. AU - Liang, Yu Chih. AU - Lin, Chien-Huang. AU - Teng, Che Ming. AU - Lee, Wen Sen. PY - 2003/7/15. Y1 - 2003/7/15. N2 - This study was designed to investigate the effect of YC-1, 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole, in human umbilical vein endothelial cells (HUVECs) proliferation and its underlying mechanism. YC-1 at a range of concentrations (5-50μM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a dose- and time-dependent manner. YC-1 was not cytotoxic at these concentrations. [3H]thymidine incorporation and flow cytometry analyses revealed that YC-1 treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Western blot analysis demonstrated that YC-1 (5-50μM) increased the levels of cyclin-dependent kinase (CDK)-inhibitory proteins ...
Tisdale, M J. and Phillips, B J., "Apparent correlation between adenosine 3.5 Cyclic monophosphate levels and malignancy in somatic cell hybrids." (1974). Subject Strain Bibliography 1974. 1875 ...
Treatment of pancreatic islets with interleukin 1 (IL-1) results in a time-dependent inhibition of glucose-stimulated insulin secretion which has recently been demonstrated to be dependent on the metabolism of L-arginine to nitric oxide. In this report IL-1 beta is shown to induce the accumulation of cyclic GMP (cGMP) in a time-dependent fashion that mimics the time-dependent inhibition of insulin secretion by IL-1 beta. The accumulation of cGMP is dependent on nitric oxide synthase activity, since NG-monomethyl-L-arginine (a competitive inhibitor of nitric oxide synthase) prevents IL-1 beta-induced cGMP accumulation. cGMP formation and nitrite production induced by IL-1 beta pretreatment of islets are also blocked by the protein synthesis inhibitor, cycloheximide. The formation of cGMP does not appear to mediate the inhibitory effects of IL-1 beta on insulin secretion since a concentration of cycloheximide (1 microM) that blocks IL-1 beta-induced inhibition of glucose-stimulated insulin ...
In this article, we show that NO not only induces a rapid cGMP response in platelets and in aortic strips but also serves to alter the responsiveness of the cGMP cascade. In both models, the NO-induced cGMP response is biphasic and characterized by a very fast increase in cGMP, which amounts to a calculated peak concentration of ∼60 μM in platelets (see below). Subsequently, the concentration of cGMP declines rapidly, and it can be assumed that PDE activity has outcompeted cGMP synthesis. Thus, the biphasic cGMP accumulation profiles are indicative of a complex, thus far poorly understood interplay of cGMP-forming and -degrading activities.. The rapid desensitizing effect of NO is demonstrated by preincubating platelets or aortic strips, which reveals that the extent of the cGMP response is inversely related to the amount of NO present during the preincubation (Figs. 2 and 3 B). At high NO concentrations, the cGMP system becomes desensitized almost completely, whereas at low tissue ...
Background: Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP) elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG) activation. In turn, platelet phosphodiesterases (PDEs) and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation. Results: We modeled dynamically concentration-dependent responses of pathway ...
In the present study, we have shown that YC-1 induced an antiproliferative effect in HCC cells in a concentration-dependent manner. YC-1 also inhibited DNA synthesis in HA22T cells and blocked the G1-S transition of the cell cycle. It is well known that elevation of the cGMP levels can be achieved by YC-1 through direct activation of sGC (Wu et al., 1995) and by inhibition of phosphodiesterase activity (Galle et al., 1999). Nevertheless, YC-1-mediated responses through a cGMP-independent pathway have also been described before (Ferrero and Torres, 2001; Hwang et al., 2003). In our study, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (a selective sGC inhibitor) and KT-5823 (a selective inhibitor of cGMP-dependent protein kinase) did not prevent the YC-1-induced antiproliferative effect, nor did YC-1 increase cGMP formation in HA22T cells. These results suggest that YC-1-induced inhibition of HA22T proliferation occurs through a cGMP-independent signaling pathway. Soluble guanylyl cyclase is a ...
PDE-stable cyclic GMP analogue suitable for immobilization as affinity ligand (e.g. for purification of phosphodiesterases) or for coupling of various labelling structures including fluorophores. This structure is also offered as a ligand immobilized to a
c-di-GMP is a ubiquitous bacterial second messenger that regulates motility, biofilm formation, and virulence of many bacterial pathogens. The PilZ domain is a widespread c-di-GMP receptor that binds c-di-GMP through its RXXXR and [D/N]hSXXG motifs; some PilZ domains lack these motifs and are unable to bind c-di-GMP. We used structural and sequence analysis to assess the diversity of PilZ-related domains and define their common... ...
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BioAssay record AID 607603 submitted by ChEMBL: Inhibition of mouse PDE10A assessed as inhibition of hydrolysis of [3H]cGMP to [3H]GMP after 20 mins by scintillation counting.
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Two disparate mechanisms have evolved for activating PKG1α; one relies on binding of the second messenger cGMP, the other involves thiol oxidation inducing a disulfide homodimer. In this study, we found that these 2 mechanisms of activating PKG1α are intricately linked with the binding of cGMP preventing oxidation to the disulfide state. The N-terminus of PKG1α, which contains the redox-sensitive cysteine from each monomer of the dimer, have been mapped using NMR.14 This structural information shows that the redox cysteines in PKG1α are in close proximity and orientated to allow the formation of a disulfide bond when oxidants are present. Our observations are consistent with cGMP binding to PKG1α causing an allosteric structural change that reorientates the redox cysteines. This reorientation presumably moves the thiols too far apart or changes their molecular environment such that their pKa is increased to lower their reactivity with oxidants, either of which would attenuate disulfide ...
Publications, Scientific Experts, Research Topics, Species, Genomes and Genes, Research Grants about cyclic gmp dependent protein kinases
Kaupp, U.B., Niidome, T., Tanabe, T., Terada, S., Bonigk, W., Stuhmer, W., Cook, N.J., Kangawa, K., Matsuo, H., Hirose, T. 1989 Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature, 342, 762 766 ...
Today we residents are post-inservice exam, put together by The American Board of Emergency Medicine, and I can say this about the test: Im glad Im not an intern anymore. Ive obviously still got a lot to learn, but its nothing like the feeling of overwhelmth (yes, just made that up) you feel halfway through your internship thinking, "Im supposed to know the answer to this?". But today Im not writing about those mushy-gushy feelings and experiences. No no. Today, I want answers.. I was always annoyed with standardized medical tests (primarily the USMLE) where you left the exam with a) no idea how you performed and b) no real feedback for several months. At this point, I dont really care if I missed a question about cyclic GMP on USMLE Step I, but for the inservice exam, its a different story. This is stuff that I apparently need to know. And so, please, ABEM: I want to know the right answers.. If the point of the inservice and the boards is knowledge and learning and requiring a certain ...
The cyclic nucleotide cGMP has been shown to play important roles in plant development and responses to abiotic and biotic stress. To date, the techniques that are available to measure cGMP in plants are limited by low spatial and temporal resolution. In addition, tissue destruction is necessary. To circumvent these drawbacks we have used the δ-FlincG fluorescent protein to create an endogenous cGMP sensor that can report cellular cGMP levels with high resolution in time and space in living plant cells. δ-FlincG in transient and stably expressing cells shows a dissociation constant for cGMP of around 200 nm giving it a dynamic range of around 20-2000 nm. Stimuli that were previously shown to alter cGMP in plant cells (nitric oxide and gibberrellic acid) evoked pronounced fluorescence signals in single cells and in root tissues, providing evidence that δ-FlincG reports changes in cellular cGMP in a physiologically relevant context. ...
Summary of work for this project as indicated on the report: Evidence for a new type of PGE1 receptor coupled to cGMP accumulation was obtained. Cell lines with PGE1 receptors coupled only to cAMP were found as well as cell lines with 2 species of PGE1 receptors, one coupled to cAMP accumulation, the other to cGMP accumulation. The 2 species of PGE1 receptors also desensitize at different rates. These results show that the coupling of PGE1 to increases in cAMP and cGMP levels are clonally inherited properties which can be expressed independently ...
The MACS GMP PepTivator AdV5 Hexon is a peptide pool that consists mainly of 15-mer peptides with eleven amino-acid overlap. It has been developed for efficient in vitro stimulation and subsequent isolation AdV5 hexon-specific CD4+ and CD8+ T cells. - Schweiz
IC87201, an inhibitor of PSD95-nNOS protein-protein interactions, suppresses NMDAR-dependent NO and cGMP formation....Quality confirmed by NMR,HPLC & MS.
use Math::Prime::Util::GMP :all; my $n = 115792089237316195423570985008687907853269984665640564039457584007913129639937; # This doesnt impact the operation of the module at all, but does let you # enter big number arguments directly as well as enter (e.g.): 2**2048 + 1. use bigint; # These return 0 for composite, 2 for prime, and 1 for probably prime # Numbers under 2^64 will return 0 or 2. # is_prob_prime does a BPSW primality test for numbers , 2^64 # is_prime adds some MR tests and a quick test to try to prove the result # is_provable_prime will spend a lot of effort on proving primality say $n is probably prime if is_prob_prime($n); say $n is , qw(composite prob_prime def_prime)[is_prime($n)]; say $n is definitely prime if is_provable_prime($n) == 2; # Miller-Rabin and strong Lucas-Selfridge pseudoprime tests say $n is a prime or spsp-2/7/61 if is_strong_pseudoprime($n, 2, 7, 61); say $n is a prime or slpsp if is_strong_lucas_pseudoprime($n); say $n is a prime or eslpsp if ...
... ,cGMP Safe Deposit Service ECACC is able to accept cell lines produced according to the requirements of cGMP for cryo-storage. The cell lines must be accompanied by a certificate to confirm they have been produced in accordance with the requirements of cGMP and that they have been tested for freed,biological,biology supply,biology supplies,biology product
We follow current GMP.. For us, every project is important whether it is compendial testing or non- compendial testing. We ensure to live up to clients expectations for the project and deliver the project according to pre-decided timeline ...
در تحقیق حاضر، به منظور ارزیابی شاخص های تحمل به خشکی در ارقام کلزا و ارتباط آن ها با نشانگر های ISSR، 12 ژنوتیپ با استفاده از آزمایش فاکتوریل بر پایه طرح بلوک های کامل تصادفی در 3 سطح آبیاری (شاهد و آبیاری بعد از تخلیه 60 و 85 درصد رطوبت) در گلخانه ی دانشگاه محقق اردبیلی مورد بررسی قرار گرفتند. ارزیابی ژنوتیپ ها از نظر تحمل به خشکی توسط شاخص های کمی شامل میانگین حسابی (MP)، میانگین هندسی (GMP)، حساسیت به تنش (SSI)، تحمل به تنش (STI) و شاخص تحمل (TOL) صورت گرفت. تجزیه واریانس در هر پنج شاخص محاسبه شده مورد بررسی بر اساس طرح کاملا تصادفی در دو سطح تنش، بین ارقام اختلاف معنی دار ...
This study shows that in vitro exposure to high glucose (i.e., 25 mmol/L) of platelets from healthy subjects reduces the antiaggregating action of aspirin, an effect blunted by the antioxidant agent amifostine. It also shows that high glucose does not affect the ability of aspirin to inhibit thromboxane synthesis but impairs the ability of aspirin to activate the NO/cGMP/PKG pathway. Furthermore, it demonstrates that high glucose per se does not influence platelet aggregation in response to agonists, thromboxane synthesis, and the NO/cGMP/PKG pathway.. Thus, high glucose reduces the antiaggregating properties of aspirin only at very high concentrations; the extent of inhibition, although significant, is modest. In our experimental conditions, we did not observe the dramatic dose-dependent inhibition of platelet sensitivity to aspirin described by other authors (17,19).. Is it possible to translate results obtained in vitro to in vivo conditions? It is interesting to observe that the lack of ...
Previous studies suggested that salt-induced hypertension that develops in DS rats may be related to an inability of their renal vasculature to dilate in response to salt feeding.4 5 These earlier studies showed that compared with DR rats, DS rats have little or no reduction in RVR in response to a high salt diet before an increased TPR and hypertension develop. The renal vasculature of DS rats was hyperresponsive to the vasoconstrictors norepinephrine and angiotensin II.6 In contrast, intravenous administration of ANP or NP, vasodilators whose action depends on the production of cGMP, failed to reduce RVR in DS rats.6 The current study was designed to assess the role of cGMP production in the ability of kidneys of DR rats to vasodilate and to determine whether a deficient generation of cGMP may exist in DS rats. ANP is thought to cause renal vasodilation by activating a non-heme-containing transmembrane protein with a single subunit, so-called particulate guanylate cyclase. ANP binds to ...
Cyclic nucleotide-gated (CNG) channels mediate the transduction of light signals to electrical signals in vertebrate photoreceptors. These channels are non-selective for cations and open upon cGMP binding. The intracellular cGMP concentration is elevated in darkness, and the current through CNG channels maintains the membrane of the rod photoreceptor at around -40 mV. When light enters the retina, it triggers a signal transduction cascade that decreases intracellular cGMP, and therefore CNG channels close. A reduction in CNG current hyperpolarizes the rod. Two molecular mechanisms are crucial for the proper physiological function of retinal CNG channels. First, block of these channels by physiological agents reduces membrane noise in rods. This feature enables rods to detect photons with high sensitivity. Second, CNG channels must be able to conduct current in response to the light-triggered changes in intracellular cGMP. In other words, they should open and close gradually in response to cGMP
In enzymology, diguanylate cyclase, also known as diguanylate kinase (EC 2.7.7.65), is an enzyme that catalyzes the chemical reaction: 2 Guanosine triphosphate ↔ 2 diphosphate + cyclic di-3,5-guanylate The substrates of diguanylate cyclases (DGCs) are two molecules of guanosine triphosphate (GTP) and the products are two molecules of diphosphate and one molecule of cyclic di-3,5-guanylate (cyclic di-GMP). Degradation of cyclic di-GMP to guanosine monophosphate (GMP) is catalyzed by a phosphodiesterase (PDE). Diguanylate cyclases are characterized by the conserved amino acid sequence motifs "GGDEF" (Gly-Gly-Asp-Glu-Phe) or "GGEEF" (Gly-Gly-Glu-Glu-Phe), which constitute the domain of the DGC active site. These domains are often found coupled to other signaling domains within multidomain proteins. Often, GGDEF domains with DGC activity are found in the same proteins as c-di-GMP-specific phosphodiesterase (PDE) EAL (Glu-Ala-Leu) domains. DGC is thought to only be active as a dimer consisting ...
Cyclic GMP is synthesized in endothelial cells following ANP activation of the particulate guanylate cyclase GC-A, and also after NO-dependent activation of the soluble guanylate cyclase. The relative contributions of ANP- and NO-modulated changes in cGMP-mediated pathways are incompletely understood. We designed duplex siRNA targeting constructs to knock down selected signaling proteins in bovine aortic endothelial cells (BAEC), and explored receptor-mediated changes in cGMP pathways. ANP activation of the GC-A receptor led to an increase in intracellular cGMP content (determined by EIA) that was rapid (,2min); dose-dependent (EC50 1 nM); and robust (600-fold increase; n=3-4; all p values ,0.001). By contrast, activation of soluble guanylate cyclase by nitric oxide agonists led only to a weak (,2-fold) transient increase in endothelial cell cGMP. Increases in cGMP lead to phosphorylation of the vasodilator-stimulated phosphoprotein (VASP). ANP markedly stimulated phosphorylation of VASP Ser239, ...
The report by Castro et al demonstrates that PKG activation in response to ANP activation of pGC elicits a strong feed-forward mechanism that further enhances cGMP production in the subsarcolemmal pool (Figure). The protein target of PKG that elicits this effect is unknown. Notably, this is the first feed-forward effect to be defined for cGMP signaling in any tissue. Surprisingly, it appears that there is little activation of PDE2 activity through cGMP binding to its allosteric sites, which should counter the effect, and the mechanism for terminating the feed-forward signal is not determined. Moreover, the mechanism whereby PDE2 is selectively localized to this cGMP pool is unknown.. In contrast, increased cGMP production by NO-GC elicits the opposite effect on cGMP levels by activating a negative-feedback regulation of cytosolic cGMP; this is mediated by activation of PKG, which phosphorylates and activates PDE5. The resulting increased cGMP breakdown blunts further elevation of cGMP and lowers ...
The beneficial cardiovascular effects of aspirin are generally attributed to its immediate platelet inhibitory function. However, accumulating evidence suggests that aspirin may have additional biological properties on the vasculature that contribute to the reduction of ischemic cardiovascular events in patients with hypertension and atherosclerosis.29,30⇓ These possible nonplatelet-mediated effects include the attenuation of atherosclerosis attributable to inhibition of vascular smooth muscle cell proliferation,31 reduction in proinflammatory mediators,32 or improvement of endothelial dysfunction.33 Recent work by different groups has revealed that aspirin is capable of directly protecting the endothelium from the deleterious effects of oxidant stress.7,9⇓ The underlying mechanisms have remained obscure.. The present study demonstrates that NO, which has long been known to improve endothelial dysfunction,34-36⇓⇓ is a crucial mediator of aspirin-induced endothelial cell protection. ...
The present study demonstrates that the level of vasodilator-stimulated phosphoprotein phosphorylated at serine 239 (P-VASP) in the rabbit aortic vessel wall is an indicator of both cGK-I activity and endothelium integrity under physiological and pathophysiological conditions. It is now well established that the NO-cGMP pathway is a key regulator of vascular tone and that cGK-I mediates many of these NO/cGMP effects. Studies with cGK-I-deficient human cells and mice demonstrated that cGK-I ablation disrupts the NO/cGMP pathway in vascular cells and tissues.3 6 Gene-targeted loss of murine cGK-I abolished NO/cGMP-dependent relaxation of smooth muscle resulting in severe vascular and intestinal dysfunctions, whereas cAMP-mediated smooth muscle relaxation was not impaired.5 6 These recent developments highlight the importance of assessing cGK expression and/or cGK activity in the presence of endothelial dysfunction. However, cGMP-independent NO effects in vascular tissues exist which are not ...
1. An assay has been developed with sufficient sensitivity for determination of the adenosine 3′:5′-cyclic monophosphate diesterase activity in islets of Langerhans, and has been used to investigate the response of the enzyme to various agents which are known to affect insulin release. 2. The subcellular distribution of the enzyme in islets of Langerhans prepared from guinea-pig pancreas was investigated and over 70% of the activity present in the original homogenate was recovered in the supernatant fraction. 3. Gel filtration of the activity present in the supernatant fraction on Sephadex G-200 gave a single peak of activity with an apparent molecular weight of 200000. The phosphodiesterase activity in the peak fraction showed two apparent Km values for adenosine 3′:5′-cyclic monophosphate (cyclic AMP) of 3μm and 30μm, suggesting the presence of two activities. The pH optimum of the activity with the low Km value was 8.7. 4. Theophylline, caffeine, 3-isobutyl-1-methylxanthine ...
Howard, E F.; Scott, D F.; and Manter, J O., "Cyclic nucleotide levels in mouse mammary epithelial cells during growth arrest and growth initiation in culture." (1977). Subject Strain Bibliography 1977. 3565 ...
Defects in phosphotransferase chemotaxis in cya and cpd mutants previously cited as evidence of a cyclic GMP or cyclic AMP intermediate in signal transduction were not reproduced in a study of chemotaxis in Escherichia coli and Salmonella typhimurium. In cya mutants, which lack adenylate cyclase, the addition of cyclic AMP was required for synthesis of proteins that were necessary for phosphotransferase transport and chemotaxis. However, the induced cells retained normal phosphotransferase chemotaxis after cyclic AMP was removed. Phosphotransferase chemotaxis was normal in a cpd mutant of S. typhimurium that has elevated levels of cyclic GMP and cyclic AMP. S. typhimurium crr mutants are deficient in enzyme III glucose, which is a component of the glucose transport system, and a regulator of adenylate cyclase. After preincubation with cyclic AMP, the crr mutants were deficient in enzyme II glucose-mediated transport and chemotaxis, but other chemotactic responses were normal. It is concluded ...
Cyclic guanosine 3,5-monophosphate (cGMP)-dependent protein kinase (PKG) activates a signaling pathway that leads to vascular smooth muscle cell relaxation, a process that reduces blood pressure. This enzyme consists of a dimerization domain, autoinhibitory domain, regulatory domain, and catalytic domain1. PKG is activated by cGMP binding to two binding sites of the regulatory domain. In order to study how each of these two binding sites, A and B, contributes to PKG activation, a mutant that knocked out cGMP binding to the B site, PKG Iα E292A, was expressed in Sf9 cells and purified to apparent homogeneity. Despite the presence of this mutation, the affinity for cGMP determined by surface plasmon resonance (SPR) was unchanged. The mutant still displayed cGMP dependent activation. In addition to these cGMP-binding sites, the regulatory domain contains a switch helix motif that provides a place for crosstalk between the PKG protomers2. It is not well known how this motif affects cyclic
TY - JOUR. T1 - Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis. AU - Shaw, C.A.a. AU - Webb, D.J.a. AU - Rossi, A.G.b. AU - Megson, Ian. N1 - cited By (since 1996)4. PY - 2009. Y1 - 2009. N2 - Background: Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (?), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Methods: Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N- (2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino- 3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by ...
Adenosine 3ʹ,5ʹ-cyclic Monophosphate, 8-(4-Chlorophenylthio)-2ʹ-O-Methyl-, Sodium Salt - Calbiochem A potent, cell-permeable, and specific activator of the exchange protein activated by cyclic AMP (EPAC). - Find MSDS or SDS, a COA, data sheets and more information.
Cellular physiology of vertebrate retina Light falling on the retina excites a photopigment (rhodopsin), which then triggers an enzymatic cascade in the rod and cone photoreceptors . This cascade reduces the intracellular cGMP concentration and decreases the conductance of the photoreceptor plasma membrane. We use a variety of techniques, including intracellular and extracellular recording, patch-clamp, and fluorescent dye laser spot Ca2+ measurement, in order to understand how visual transduction is modulated by Ca2+ to produce adaptation to light and to darkness. We are also interested in mechanisms of photoreceptor degeneration during inherited retinal dystrophy in diseases like retinitis pigmentosa and Lebers amaurosis. Our work has shown that continuous activation of the visual cascade is the cause of apoptosis in some of these disorders, and that cell death is probably triggered by a prolonged decrease in Ca2+ concentration. Increases in Ca2+ can also trigger apoptosis--the photoreceptor ...
Right up until the late twentieth century, small was recognized with regards to the mode of action on the nitrate medicines beyond The reality that they appeared to cause vasodilatation by way of vascular smooth muscle mass leisure. Even so, in 1977 the pharmacologist Ferid Murad and colleagues [nine] showed that nitrate software induced stimulation of soluble guanylyl cyclase derived from rat liver and bovine tracheal easy muscle mass. In turn, this brought about a rise in the second messenger cGMP stages, which induced vascular rest. They suggested that the cGMP activation may possibly occur via NO because they had also discovered that NO by itself elevated guanylyl cyclase exercise [nine, ten ...
Author Summary Malaria parasites are single celled organisms, which must alternate between vertebrate and mosquito hosts to survive and spread. In both hosts, certain parasite stages can glide through tissues and invade cells. Many components of the molecular motor that powers gliding and invasion are known and we have a good idea how these may interact to generate force. It is less well understood how the motor is assembled and how its component parts are regulated to switch it on and off. We have begun to address these questions in the ookinete, a parasite stage, which forms in the blood meal of a mosquito and relies on gliding to penetrate the gut wall. Using a malaria parasite of rodents, we have examined the effect of deleting candidate genes involved in controlling levels of the intracellular signalling molecule cyclic guanosine monophosphate (cGMP). We show that the right balance between cGMP production and degradation is important for ookinetes to glide, while also maintaining their typical cell
НИИ атеросклероза: научные исследования, публикации сотрудников института (abstracts, full-text.), дискуссионный клуб, посвященный вопросам механизмов атерогенеза.
To date, just one structural class of cyclic nucleotide receptors has been characterized, that comprises the bacterial CAP (McKay and Steitz, 1981), the cyclic nucleotide‐regulated protein kinases PKG and PKA (Weber et al., 1989; Su et al., 1995) and the cyclic nucleotide‐gated ion channels (Altenhofen et al., 1991; Kumar and Weber, 1992). This class has been referred to as the cNMP domain family (Schultz et al., 1998). The GAF domains of the cGMP‐regulated PDEs represented a potentially different class of cyclic nucleotide receptors, since they lacked any sequence homology to the cNMP motif. The structure of the YKG9 protein shows no similarity to the cNMP domain and thus establishes beyond any doubt that there are at least two entirely different structural classes of cyclic nucleotide receptors.. The YKG9 structure provides a three‐dimensional template for modeling other GAF domains, including those of the PDEs. The use of multiple threading alignment based on the solved structure ...
While human and mouse genetics consistently have unveiled various physiological roles of members of the pGC family, overall the mode of ligand‐dependent as well as ligand‐independent activation of these transmembrane enzymes leading to intracellular cGMP synthesis remains enigmatic. The intracellular region of pGCs consists of a juxtamembranous protein kinase-homology domain, an amphipathic α‐helical or hinge region, and the C‐terminal cyclase catalytic domain (Fig 1) (reviewed by Potter, 2011). The hinge region is involved in higher order oligomerization. Hence, although pGCs contain a single cyclase site per polypeptide chain, receptor dimerization is essential for the activation of this cGMP‐synthesizing domain (Potter, 2011). The crystal structures of the extracellular domain of GC‐A, in complex with atrial natriuretic peptide, or in absence of the ligand, suggested that hormone binding induces a rotation of the juxtamembrane domains, which is transmitted across the ...
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Myc-DDK-tagged ORF clone of Homo sapiens guanosine monophosphate reductase 2 (GMPR2), transcript variant 4 as transfection-ready DNA - 10 µg - OriGene - cdna clones
110345-37-4 - VJLCRYXVRYNFKK-UHFFFAOYSA-N - 4-Morpholinepropanol, alpha-(3-fluoro-4-methoxyphenyl)-beta-phenyl-, hydrochloride - Similar structures search, synonyms, formulas, resource links, and other chemical information.
MACS GMP PepTivator BKV LT is a peptide pool that consists mainly of 15-mer peptides with 11 amino acids overlap. It has been developed for efficient in vitro stimulation and subsequent isolation of BKV LT-specific CD4+ and CD8+ T cells. - Belgique
are issues of clarity in GMP guidance required. GMP chapters and Annex guidances cannot be prescriptive on all issues and allow for development and innovation. In addition some flexibility is allowed to facilitate product and pharmaceutical processing experts to develop rationale, methodology, good practice with procedures and acceptance criteria to suit novel and specialized medicinal and therapeutic products. This PHSS GMP clarity of issues conference brings together, key opinion leaders, subject matter experts together with Ex and current GMP regulatory inspectors to debate and provide clarity on areas and topics of GMP where interpretation is challenging and shared experience within the neutral platform of the PHSS conference provides an opportunity to understand approaches and expectations to GMP compliance.. More detail to follow soon.. ...
The inclusion of new feed materials, changes in product names or removal of feed materials also effects the GMP+ Monitoring database (MDB). For new feed materials it is possible to add analytical results from now on. When a product name is changed the name will also change in the GMP+ MDB. For the removed feed materials it is no longer possible to add analytical results, but the historical analytical results will still be available for consultation ...
21 ​CFR ​111 ​Dietary ​Supplement ​GMP ​Overview ​- ​Cost: ​Current ​NSF ​GMP ​Client ​- ​$1000; ​Non-GMP ​Client ​- ​$1400; ​UNPA ​Member ​- ​$1260/Per ​Person. ​ ​This ​extensive ​2-day ​training ​c
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
References for Abcams Adenosine 3′,5′-cyclic monophosphate (cAMP) (ab120493). Please let us know if you have used this product in your publication
erp ENTERPRISE-WIDE RESOURCE PLANNING - AGENDA zTHE CASE FOR ERP : yBUSINESS CASE yTHE I.T. ANGLE zERP DEFINITIONS, EVOLUTION zERP COMPONENTS zINVESTING IN ERP zIMPLEMENTATION ISSUES
Whenever equipment is repaired or spare part is replaced. it should be calibrated before being put into use for routine work. Following steps to be taken in regards to the qualification of the said ...
وَأمّا حَقُّ المُشِيرِ عَلَيْكَ فَلا تتَّهِمْهُ فِيمَا لا يُوافِقُكَ عَلَيهِ مِنْ رَأْيِهِ إذا أَشَارَ عَلَيْكَ فَإنَّمَا هِيَ الآرَاءُ وَتصَرُّفُ النَّاسِ فِيهَا وَاختِلافُهُمْ. فَكُنْ عَلَيهِ فِي رَأيِهِ بالخِيَارِ إذا اتَّهمْتَ رَأْيَهُ، فَأَمّا تُهْمتُهُ فَلا تَجُوزُ لَكَ إذَا كَانَ عِنْدكَ مِمَّنْ يَسْتَحِقُّ الْمُشَاوَرَةَ. وَلا تَدَعْ شُكْرَهُ عَلَى مَا بَدَا لَكَ مِن إشْخاصِ رَأْيِهِ وَحُسْنِ وَجْهِ مَشُورَتِهِ، فَإذا وَافَقَكَ حَمِدتَ اللَّهَ وَقَبلْتَ ذلِكَ مِن أَخِيكَ بالشُّكْرِ والإرْصَادِ بالْمُكَافَأَةِ فِي مِثلِهَا إنْ ...
TY - JOUR. T1 - Phosphorylation of tyrosine hydroxylase by cyclic GMP - Dependent protein kinase. AU - Roskoski, R.. AU - Vulliet, Philip R. AU - Glass, D. B.. PY - 1987. Y1 - 1987. N2 - Tyrosine hydroxylase purified from rat pheochromycytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. The extent of activation was correlated with the degree of phosphate incorporated into the enzyme. Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP-dependent protein kinases. The enzymes appeared to mediate the phosphorylation of the same residue based on the observation that incorporation was not increased when both enzymes were present. The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following ...
Abstract: Treatment of rat cerebellar astrocyte-enriched primary cultures with dexamethasone enhances the nitric oxide-dependent cyclic GMP formation induced by noradrenaline in a time-(,6 h) and concentration-dependent manner (half-maximal effect at 1 nM). Stimulation of cyclic GMP formation by the calcium ionophore A23187 is similarly enhanced. In contrast, cyclic GMP accumulation in cells treated with lipopolysaccharide is inhibited by dexamethasone. The potentiating effect of dexamethasone is prevented by the protein synthesis inhibitor cycloheximide and is not due to increased soluble guanylate cyclase activity. Agonist stimulation of [3H]arginine to [3H]citrulline conversion is enhanced by dexamethasone in astrocytes but not in cerebellar granule cells. These results indicate that glucocorticoids may up-regulate astroglial calcium-dependent nitric oxide synthase while preventing expression of inducible nitric oxide synthase and are the first report of a differential long-term regulation of ...
The existence of cyclic GMP phosphodiesterase (EC 3.1.4.-) was demonstrated in silkworm larva by gel filtration of the homogenate. The cyclic GMP phosphodiesterase was separated from cyclic AMP phosphodiesterases by column chromatography on hydroxyapatite and Sephadex G-200. The enzyme ...read more ...
The expression and phosphorylation state of VASP was investigated in neutrophils during cell adherence. Adhesion is an essential process for neutrophil migration from the peripheral blood to sites of inflammation. During the process of adhesion, neutrophils adhere and spread without any clear stopping point between these two processes. Therefore, it was important to determine whether VASP was phosphorylated in response to signals involved in adhesion and/or spreading. In this report, we demonstrate that VASP is a target for cGK regulation of neutrophil spreading. We showed that VASP was in its dephosphorylated form in retracted round neutrophils and was rapidly phosphorylated by cGK at the onset of cell spreading. Both adherence and the onset of cell spreading induced significant elevations of cGMP in neutrophils. When neutrophils were incubated with 8-Br-cGMP, a direct activator of cGK, cells became more polarized in suspension, and spread more rapidly during adhesion. Our observations that ...
Previously, our lab showed that low-level nitric oxide (NO) and downstream activation of the cGMP/protein kinase G (PKG) signaling pathway plays a key role in preventing spontaneous apoptosis and stimulating proliferation in many mammalian cells, including neural cells, vascular smooth muscle cells and certain tumor cells (e.g. human ovarian cancer cells). In cancer cells, PKG is hyper-activated, which may contribute to rapid cell proliferation and resistance to chemotherapy. Recently, our lab found that two mesothelioma cell lines (MSTO-211H and NCI-H2452 cells) and two prostate cancer cell lines (PC-3 and DU145 cells) also show dependence on endogenous NO/cGMP/PKG pathway for promoting proliferation and cell survival (contributing to cisplatin-resistance). Pharmacological blocking of either NO-induced cGMP synthesis (using ODQ) or PKG enzymatic activity (using DT-2) in mesothelioma and prostate cancer cells decreases proliferation rate, increases apoptosis and sensitizes cells to cisplatin. ...
1. The effect of a α-human atrial natriuretic peptide (1-28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo.. 2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques.. 3. ANP (0.1-1 μg/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 μg/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme.. 4. ANP (1 nmol/l-1 μmol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein.. 5. ANP ...
Sigma-Aldrich offers abstracts and full-text articles by [Kislay Parvatiyar, Zhiqiang Zhang, Rosane M Teles, Songying Ouyang, Yan Jiang, Shankar S Iyer, Shivam A Zaver, Mirjam Schenk, Shang Zeng, Wenwan Zhong, Zhi-Jie Liu, Robert L Modlin, Yong-jun Liu, Genhong Cheng].
The cyclic nucleotides cAMP and cGMP are common signaling molecules synthesized in neurons following the activation of adenylyl or guanylyl cyclase. In the striatum, the synthesis and degradation of cAMP and cGMP is highly regulated as these second messengers have potent effects on the activity of striatonigral and striatopallidal neurons. This review will summarize the literature on cyclic nucleotide signaling in the striatum with a particular focus on the impact of cAMP and cGMP on the membrane excitability of striatal medium-sized spiny output neurons (MSNs). The effects of non-selective and selective phosphodiesterase (PDE) inhibitors on membrane activity and synaptic plasticity of MSNs will also be reviewed. Lastly, this review will discuss the implications of the effects PDE modulation on electrophysiological activity of striatal MSNs as it relates to the treatment of neurological disorders such as Huntingtons and Parkinsons disease.
This superfamily comprises nucleotide cyclase structural domains, specifically a catalytic domain found in adenylate and guanylate cyclases. It has a ferredoxin-like fold with additional secondary structures, and is often known as the GGDEF domain, named after the conserved central sequence pattern GG[DE][DE]F. Though the fold of the GGDEF domain is similar to adenylate cyclase, the nucleotide-binding mode is substantially different PMID:15569936. It is typically present in multidomain proteins containing regulatory domains of signalling pathways or protein-protein or protein-ligand interaction modules, such as the response regulatory domain, the PAS/PAC domain, the HAMP domain, the GAF domain, the FHA domain or the TPR repeat. However a few single-domain proteins are also known. The GGDEF domain is involved in signal transduction and is likely to catalyse synthesis or hydrolysis of cyclic diguanylate (c-diGMP, bis(3,5)-cyclic diguanylic acid), an effector molecule that consists of two cGMP ...
THE CYCLIC NUCLEOTIDES, CAMP AND CGMP ARE IMPORTANT REGULATORY MOLECULES THAT ARE NOW RECOGNIZED AS MEDIATORS IN A VAST NUMBER OF NORMAL AND PATHOLOGICAL PROCESSES. SUCH INSIGHTS HAVE INCREASED THE NEED FOR GENERALLY AVAILABLE TECHNOLOGY THAT WILL ALLOW THE CONVENIENT AND ACCURATE MEASUREMENT OF THE CYCLIC NUCLEOTIDES IN RESEARCH AND CLINICAL SETTINGS. THIS PHASE I PROPOSAL OUTLINES OUR INTEREST IN PURSUING THE GENERATION OF MURINE MONOCLONAL ANTI CAMP/CGMP ANTIBODIES AND FLUORESCENT ENZYME IMMUNOASSAY SYSTEMS FOR THE RAPID AND SENSITIVE MEASUREMENT OF THE CYCLIC NUCLEOTIDES IN BIOLOGICAL MATERIALS. HYBRIDOMAS WILL BE PREPARED VIA FUSION OF MOUSE MYELOMA CELLS WITH SPLEENS OF MICE IMMUNIZED WITH SUCCINYL-CAMP (OR CGMP) CONJUGATED TO BOVINE SERUM ALBUMIN. RESULTANT MONOCLONAL ANTIBODIES WILL BE ATTACHED TO BETA-GALACTOSIDASE AND UTILIZED IN A RAPID SOLID-PHASE ENZYME IMMUNOASSAY USING FLUOROGENIC SUBSTRATES. THESE EXPECTED RESULTS WILL SERVE AS THE BASIS OF PHASE II, WHERE WE ENVISION THAT THE ...
Like Caulobacter, Pseudomonas produces a single polar flagellum that is partitioned to one daughter at cell division and can be visualized microscopically by labeling living cells with Alexa Fluor 594 conjugated to surface amine-specific succinimidy ester (Fig. 1C, figs. S5 and S6, and movie S1). Before cell division, the two cell poles harbored similar c-di-GMP levels, probably because of rapid diffusion of the second-messenger molecule. When septum formation resulted in two distinct cells, c-di-GMP rose above 500 nM in the nonflagellated daughter cell and dropped in the flagellated cell below 100 nM (Fig. 1C). This asymmetrical second-messenger distribution was not a stochastic event: In both organisms, c-di-GMP levels were always significantly lower in the flagellated cell than in the nonflagellated one (Fig. 1D).. Bacterial genomes encode multiple DGCs and PDEs in proteins with signal-sensing domains (fig. S4), some of which exhibit distinct subcellular localization (11-13). Thus, ...
However, in the presence of DNA or at low temperatures, the Brinker DNA binding domain (BrkDBD) adopts a well-folded structure ...
8-Nitro-cGMP (8-nitroguanosine 3′,5′-cyclic monophosphate) is a nitrated derivative of cGMP, which can function as a unique electrophilic second messenger involved in regulation of an antioxidant adaptive response in cells. In the present study, we investigated chemical and biochemical regulatory mechanisms involved in 8-nitro-cGMP formation, with particular focus on the roles of ROS (reactive oxygen species). Chemical analyses demonstrated that peroxynitrite-dependent oxidation and myeloperoxidase-dependent oxidation of nitrite in the presence of H2O2 were two major pathways for guanine nucleotide nitration. Among the guanine nucleotides examined, GTP was the most sensitive to peroxynitrite-mediated nitration. Immunocytochemical and tandem mass spectrometric analyses revealed that formation of 8-nitro-cGMP in rat C6 glioma cells stimulated with lipopolysaccharide plus pro-inflammatory cytokines depended on production of both superoxide and H2O2. Using the mitochondria-targeted chemical ...
A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the cyclic portion consists of two bonds between the phosphate group and the 3 and 5 hydroxyl groups of the sugar, very often a ribose. Their biological significance includes a broad range of protein-ligand interactions. They have been identified as secondary messengers in both hormone and ion-channel signalling in eukaryotic cells, as well as allosteric effector compounds of DNA binding proteins in prokaryotic cells. cAMP and cGMP are currently the most well documented cyclic nucleotides, however there is evidence that cCMP (cytosine) is also involved in eukaryotic cellular messaging. The role of cyclic uridine ...
Cyclic guanosine 5-monophosphate (cGMP) phosphodiesterase (PDE) regulates the level of cGMP on transduction of a visual signal in vertebrate photoreceptor cells. Two identical inhibitory PDE gamma subunits (Pgammas) block catalytic activity of PDE-alpha and -beta subunits (Palphabeta) in the dark. The primary regions of Pgamma involved in the interaction with Palphabeta are a central polycationic region, Pgamma-24-45, and a C-terminal region of Pgamma. Recently, we have shown that the C-terminal region of Pgamma, which is the major Pgamma inhibitory domain, blocks PDE activity by binding to the catalytic site of PDE (Artemyev, N. O., Natochin, M., Busman, M., Schey, K. L., and Hamm, H. E. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5407-5412). Here, we localize the site on the rod cGMP PDE alpha subunit that binds to the central polycationic domain of Pgamma. This site is located within a region that links a second noncatalytic cGMP binding site with the catalytic domain of PDE. A polypeptide ...
BioAssay record AID 630202 submitted by ChEMBL: Inhibition of retinal rod CNGA1/CNGB1 expressed in Xenopus laevis oocytes assessed as blockade of cGMP-induced current at +50 mV holding potential by patch-clamp electrophysiology.
A small molecule is associated with rhodopsin called 11-cis retinal. This small molecule absorbs light and isomerizes to all-trans retinal. As a result, it induces a conformational change in rhodposin protein. This activated rhodopsin then activates G protein called transducin. Being a G-protein, transducin has three subunits as α, β and γ. Just to recall, the α-subunit in inactive state is bound to GDP. Since, rhodopsin activates G protein transducin, there is a conformational change where α-subunit is now bound to GTP and is in active state. This α-subunit (of transducin) bound to GTP then stimulates the activity of cGMP phosphodiesterase. Now, being a phosphodiesterase, it reduces the intracellular levels of cGMP. The cGMP has a direct effect on ion channels in plasma membrane and so when there is reduction of cGMP levels in the rod cells of retina, this is translated to nerve impulse as light by the effect of cGMP on ion channels ...
the objective of this investigation was to study the effect of the presence of red blood cells (RBCs) in the plasma layer adjacent to the arteriole wall on coupled nitric oxide (NO) and oxygen (O2) transport using computer simulations and to compare our model predictions with experimental data from the literature.. NO, produced by endothelial cells lining the vessel wall, diffuses both into the vessel lumen and to surrounding tissues. Most endothelium-derived NO is scavenged by hemoglobin in the RBCs in the bloodstream, and only a portion diffuses abluminally. The portion that diffuses into the vessel wall activates soluble guanylate cyclase (sGC), catalyzing the formation of cyclic 3′,5′-guanosine monophosphate and activating cyclic 3′,5′-guanosine monophosphate-dependent protein kinase. This results in a decrease of Ca2+ inside smooth muscle cells and dephosphorylation of contractile proteins, such as myosin light chain, causing relaxation of vascular smooth muscle (8, 24). Generation ...
The effects of extracellularly applied 3′-5′ cyclic guanosine monophosphate (cGMP) on kainate responses from cultured cerebellar granule and Purkinje neurons were investigated using whole-cell and outside-out patch recording modes. Cerebellar granule cell responses to kainate were not homogeneous, nor were the effects of cGMP. Therefore, effects of cGMP are described for two groups of granule cells categorized on the basis of the underlying channel conductance estimated by variance analysis. Cells with high-noise kainate responses had average channel conductances of 5 to 7 picoseimens, whereas the average conductances of low-variance noise responses were 0.3 to 2.0 picoseimens. High-noise kainate responses were inhibited by externally applied cGMP (5-1000 μM) in a rapidly reversible and dose-dependent manner. IC50 values were estimated at ∼150 μM cGMP for 25 μM kainate and ∼500 μM cGMP for 100 μM kainate. Evidence that cGMP-mediated inhibition of high-noise kainate responses ...
A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the bodys production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the th
MEDICATIONS. Mechanism of actions of current medications are based on modulation of the intracellular calcium through enhancement of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). a. Inhalation therapies:. Inhaled Nitric Oxide (NO): Activates Guanylyl cyclase; that transforms GTP (guanosyn triphosphate) into cGMP. cGMP activates Protein kinase G (PKG). PKG has several actions: it can directly decrease the entrance of calcium into the muscle cell, decreases the release of calcium from the sarcoplasmic reticulum (SR). It also phosphorylates the kinase that transforms light myosin chains in activated chains. All of this results in decreased intracellular calcium in the muscle cell and causes relaxation. Prostacyclin analogs (Iloprostol): mimetic PGE2 actions. Activate adenyl cyclase increasing cAMP . cAMP activates protein kinase A. PKA has several actions: phosphorylation of several membrane proteins that produce relaxation; inactivates the kinase that ...
This cGMP effect on DRG axon branching is specific, because 8-bromoadenosine-3′,5′-cyclic monophosphate (8-Br-cAMP), an equivalent analog to activate the cAMP pathway, did not elicit the same effect (Fig. 1G-I). Neither the distribution nor the average number of branching points changed significantly in the 8-Br-cAMP-treated culture compared with the untreated one (Fig. 1N,P). Furthermore, YC-1, a small molecule that activates the soluble guanylyl cyclase (sGC) to produce cGMP (Galle et al., 1999), induced branch formation in a dose dependent manner, reaching a similar level as in the 8-Br-cGMP-treated culture (Fig. 1J-L,O,P). Conversely, Zaprinast, an inhibitor that prevents cGMP degradation by phosphodiesterase-5 (Dundore et al., 1993), also induced branching (data not shown).. We further examined several parameters to determine if the in vitro effect reflects the role of cGMP signaling in axon growth or branching. First, neurons from the control cultures had a total length (Lt) of 254 ± ...
Phosphodiesterases (PDEs) are enzymes that play a major role in cell signalling by hydrolysing the secondary messengers cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) throughout the body and brain. Altered cyclic nucleotide-mediated signalling has been associated with a wide array of disorders, including neurodegenerative disorders. Recently, PDE5 has been shown to be involved in neurodegenerative disorders such as Alzheimers disease, but its precise role has not been elucidated yet. To visualize and quantify the expression of this enzyme in brain, we developed a radiotracer for specific PET imaging of PDE5. A quinoline-based lead compound has been structurally modified resulting in the fluoroethoxymethyl derivative ICF24027 with high inhibitory activity towards PDE5 (IC50 = 1.86 nM). Radiolabelling with fluorine-18 was performed by a one-step nucleophilic substitution reaction using a tosylate precursor (RCY(EOB) = 12.9% ± 1.8%; RCP > 99%; SA(EOS) = 70-126 GBq
Results sGC stimulation inhibited TGFβ-dependent fibroblast activation and collagen release. sGC knockout fibroblasts confirmed that the sGC is essential for the antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGFβ-dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter activity and transcription of classical TGFβ target genes remained unchanged, sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation inhibited TGFβ-driven dermal fibrosis but did not change p-SMAD2 and 3 levels and TGFβ target gene expression, confirming that non-canonical TGFβ pathways mediate the antifibrotic sGC activity. ...
Global rearrangement of the riboswitch induced by c-di-GMP binding. (a) Low-resolution molecular envelope reconstruction based on SAXS data of the riboswitch in
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Francois Paquet-Durand, Ph.D., the projects scientific coordinator, said that DRUGSFORDs lead therapy candidate has shown efficacy in the RD1 mouse - a model of severe, early onset retinitis pigmentosa (PDE6B mutations). The consortium is generating additional safety and efficacy data required for a clinical trial it hopes to launch at the end of 2015.. Developed by the German company BIOLOG, the active therapeutic molecule targets the signaling of a chemical in photoreceptors called cyclic guanosine monophosphate, or cGMP. While the name is a mouthful, the chemical plays a fundamental role in vision. Photoreceptors need the right amount of cGMP to send electrical signals with visual information back to the brain. And it just so happens that vision loss from retinal degenerations is often caused by the production of too much or too little cGMP. So, the therapeutic molecule is designed to re-balance cGMP signaling.. In addition to creating a drug that addresses a common disease pathway, ...
In humans, the cGAS-STING signaling pathway is essential for immunity to diverse pathogens. Upon recognition of foreign DNA, the enzyme cGAS catalyzes formation of cyclic GMP-AMP (cGAMP), a second-messenger cyclic dinucleotide that activates the receptor STING to initiate an immune gene expression program. Due to broad tissue tropism and the ability to potently respond to natural small-molecules, STING is a rapidly emerging target for cancer immunotherapy. Using a structural and biochemical approach, we are working to determine the mechanisms of cGAS-STING signaling ...
The Company has previously reported about the Shelton light industrial building that will house the cGMP pilot production plant, research laboratories, and offices. The cGMP pilot plant is being designed for the production of sufficient quantities of the drug needed for human clinical trials for each of the various nanoviricides® drug candidates as they advance into the clinical pipeline. The light industrial building at 1 Controls Drive, Shelton CT was purchased by Inno-Haven, LLC. Inno-Haven is a private company that was founded by Dr. Anil R. Diwan, the Companys CEO, and financed by himself and certain of his friends and associates, with the specific purpose of enabling clinical cGMP manufacturing capabilities for NanoViricides, Inc. drug substances. Acquisition of this 18,000 sqft building on 4.2 acres of land was previously announced by NanoViricides, Inc. in September, 2011. Renovation of the building is to be performed as per the requirements of NanoViricides, Inc. for the production of ...
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At the joint ELRIG SBS meeting in 2008 The Automation Partnership (TAP) will be demonstrating the new GMP validatable Fill-It™ system for rapid dispensing of cell suspensions and liquids into screw-cap microtubes.
Researchers have developed the first chemiluminescent biosensors for measuring cyclic di-GMP, which interacts with cell signaling networks, in bacteria.
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We have variety OEM products to meet your companys requirement. The Products are manufactured in GMP certificated facility and we could conduct third party test as you requirement. Please contact us at [email protected] for more information.. ...
NMDA and nitric oxide act through the cGMP signal transduction pathway to repress hypothalamic gonadotropin-releasing hormone gene expression.s profile, publications, research topics, and co-authors
Vardenafil (Levitra) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5
TY - JOUR. T1 - Phosphorylation of cardiac troponin by guanosine 3. T2 - 5-monophosphate-dependent protein kinase. AU - Blumenthal, D. K.. AU - Stull, J. T.. AU - Gill, G. N.. PY - 1978. Y1 - 1978. N2 - Homogeneous cGMP-dependent protein kinase catalyzes the rapid incorporation of phosphate, specifically into the inhibitory subunit of purified cardiac troponin with a maximal incorporation of 1 mol of phosphate/mol of troponin. When troponin was incubated in the presence of both cGMP- and cAMP-dependent protein kinases, a maximal incorporation of 1 mol of phosphate/mol of troponin was observed which suggested phosphorylation of the same site by the two kinases. Both cyclic nucleotide-dependent kinases had similar K(m) values for troponin, but the V(max) value for the phosphorylation reaction catalyzed by cAMP-dependent protein kinase was 12-fold greater than the value obtained for cGMP-dependent protein kinase.. AB - Homogeneous cGMP-dependent protein kinase catalyzes the rapid incorporation of ...
TY - JOUR. T1 - Prevention of nitric oxide synthase induction in vascular smooth muscle cells by microtubule depolymerizing agents. AU - Marczin, Nándor. AU - Papapetropoulos, Andreas. AU - Jilling, Tamás. AU - Catravas, John D.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - We investigated the role of microtubules in the induction of nitric oxide synthase in cultured vascular smooth muscle cells. We found that like interleukin‐1α, lipopolysaccharide elicited a time and concentration‐dependent accumulation of cyclic GMP via induction of nitric oxide synthase. Nocodazole and colchicine, two chemically distinct microtubule depolymerizing agents, completely prevented lipopolysaccharide‐ and interleukin‐induced (and nitric oxide‐mediated) cyclic GMP generation. In contrast to lipopolysaccharide and interleukin‐1α, cyclic GMP accumulation in response to sodium nitroprusside, an exogenous nitrovasodilator, was not altered by either nocodazole or colchicine. Our findings demonstrate that ...
TY - JOUR. T1 - C-type natriuretic peptide/guanylate cyclase B system in ATDC5 cells, a chondrogenic cell line. AU - Suda, Michio. AU - Tanaka, Kiyoshi. AU - Yasoda, Akihiro. AU - Komatsu, Yasato. AU - Chusho, Hideki. AU - Miura, Masako. AU - Tamura, Naohisa. AU - Ogawa, Yoshihiro. AU - Nakao, Kazuwa. PY - 2002/12/1. Y1 - 2002/12/1. N2 - Natriuretic peptides constitute a family of three structurally related peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Particulate guanylate cyclases, GC-A, and GC-B, are the receptors for these peptides to mediate their action. ANP and BNP possess high affinities for GC-A, and CNP is the preferred ligand for GC-B. In this article, we report our study of the expression and possible role(s) of natriuretic peptides in ATDC5 cells, which represent a chondrogenic cell line. ATDC5 cells produced cyclic guanosine monophosphate (cGMP) in response to natriuretic peptides. CNP was far more potent than ANP ...
TY - JOUR. T1 - Human C-type natriuretic peptide. AU - Ogawa, Yoshihiro. AU - Nakao, Kazuwa. AU - Nakagawa, Osamu. AU - Komatsu, Yasato. AU - Hosoda, Kiminori. AU - Suga, Shin Ichi. AU - Arai, Hiroshi. AU - Nagata, Kiyoshi. AU - Yoshida, Nobuo. AU - Imura, Hiroo. PY - 1992/6. Y1 - 1992/6. N2 - We isolated the human C-type natriuretic peptide gene and identified the peptide in the brain. The human C-type natriuretic peptide gene appeared to be composed of at least two exons and one intron. In the 5′-flanking region, there is an array of cis elements (an inverted CCA AT box, two GC boxes, and a cyclic AMP response element-like sequence) that is not present in upstream sequences of the atrial and brain natriuretic peptide genes. Analysis of the deduced amino acid sequence revealed that human prepro C-type natriuretic peptide comprises 126 amino acids and that the C-terminal 22-residue peptide (G-L-S-K-G-C-F-G-L-K-L-D-R-I-G-S-M-S-G-L-G-C) preceded by Lys-Lys is identical to the porcine ...
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Cyclic di-GMP - WikipediaCyclic di-GMP - Wikipedia

... to be regulated by cyclic di-GMP. Riboswitches called the cyclic di-GMP-I riboswitch and cyclic di-GMP-II riboswitch regulate ... Cyclic di-GMP (also called cyclic diguanylate and c-di-GMP) is a second messenger used in signal transduction in a wide variety ... The PilZ domain has been shown to bind cyclic di-GMP and is believed to be involved in cyclic di-GMP-dependent regulation, but ... In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by ...
more infohttps://en.wikipedia.org/wiki/Cyclic_di-GMP

Cyclic GMP-AMP synthase - WikipediaCyclic GMP-AMP synthase - Wikipedia

"Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase". Cell. 153 (5 ... Gao, D; Wu, J; Wu, YT; Du, F; Aroh, C; Yan, N; Sun, L; Chen, ZJ (Aug 23, 2013). "Cyclic GMP-AMP synthase is an innate immune ... Wu, J; Sun, L; Chen, X; Du, F; Shi, H; Chen, C; Chen, ZJ (Dec 20, 2012). "Cyclic GMP-AMP is an endogenous second messenger in ... Sun, L; Wu, J; Du, F; Chen, X; Chen, ZJ (Dec 20, 2012). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the ...
more infohttps://en.wikipedia.org/wiki/Cyclic_GMP-AMP_synthase

STING is a direct innate immune sensor of cyclic di-GMP.  - PubMed - NCBISTING is a direct innate immune sensor of cyclic di-GMP. - PubMed - NCBI

... c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP ... STING is a direct innate immune sensor of cyclic di-GMP.. Burdette DL1, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, ... IFN induction by transfected cyclic-di-GMP and VV 70-mer dsDNA was measured by qRT-PCR and normalized to ribosomal protein 17 ( ... c and d, HEK293T cells were transfected as in a and cell lysates were UV-crosslinked to c-di-GMP32 or GTP32 in the presence of ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/21947006?dopt=Abstract

RCSB PDB - Protein Feature View 









 - Cyclic GMP-AMP synthase - Q8N884 (CGAS HUMAN)RCSB PDB - Protein Feature View - Cyclic GMP-AMP synthase - Q8N884 (CGAS HUMAN)

Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP (PubMed:23258413, PubMed: ... ATP + GTP = 2 diphosphate + cyclic G-P2-5A-P3-5. UniProt ...
more infohttp://www.rcsb.org/pdb/protein/Q8N884

cyclic gmp dependent protein kinasescyclic gmp dependent protein kinases

Research Grants about cyclic gmp dependent protein kinases ... cyclic gmp*nitric oxide*guanylate cyclase*cyclic amp dependent ... cyclic gmp dependent protein kinases. Summary. Summary: A group of enzymes that are dependent on cyclic GMP and catalyzes the ... A novel cyclic GMP-dependent protein kinase is expressed in the ring stage of the Plasmodium falciparum life cycle. Wensheng ... Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan in C elegans. Takashi Hirose. Department of Biology, ...
more infohttps://www.labome.org/topics/chemicals/and/peptides/intracellular/cyclic/cyclic-gmp-dependent-protein-kinases-13214.html

Wnt Signaling, Ca2+, and Cyclic GMP: Visualizing Frizzled Functions | ScienceWnt Signaling, Ca2+, and Cyclic GMP: Visualizing Frizzled Functions | Science

Wnt Signaling, Ca2+, and Cyclic GMP: Visualizing Frizzled Functions Message Subject. (Your Name) has forwarded a page to you ... and decreasing intracellular concentrations of cyclic guanosine monophosphate (cGMP). Heterotrimeric guanine nucleotide-binding ...
more infohttp://science.sciencemag.org/content/300/5625/1529

Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin.  - PubMed - NCBIRhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin. - PubMed - NCBI

The protein S-modulin (M(r) 26,000) is known to increase the fraction of light-activated cyclic GMP-phosphodiesterase (PDE) at ... When light is absorbed by the rods, a phosphodiesterase is activated that hydrolyses cyclic GMP. A light-induced decrease in ... Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin.. Kawamura S1. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/8386803

Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP | ScienceRiboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP | Science

Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP. By N. Sudarsan, E. R. Lee, Z. Weinberg, R. H. Moy, J. N. ... Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP. By N. Sudarsan, E. R. Lee, Z. Weinberg, R. H. Moy, J. N. ... Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP Message Subject. (Your Name) has forwarded a page to you ... The bacterial second messenger cyclic di-guanosine monophosphate controls a wide variety of cellular functions by acting on a ...
more infohttp://science.sciencemag.org/content/321/5887/411.full

Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells | DiabetesCyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells | Diabetes

Interleukin-1 beta effects on cyclic GMP and cyclic AMP in cultured rat islets of Langerhans-arginine-dependence and ... Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells. Veronika Leiss, Andreas Friebe, Andrea Welling, Franz ... Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells. Veronika Leiss, Andreas Friebe, Andrea Welling, Franz ... Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells Message Subject (Your Name) has forwarded a page to you ...
more infohttp://diabetes.diabetesjournals.org/content/60/1/148?with-ds=yes

Relationship between relaxation and cyclic GMP formation caused by nicorandil in canine mesenteric artery | SpringerLinkRelationship between relaxation and cyclic GMP formation caused by nicorandil in canine mesenteric artery | SpringerLink

Kukovetz WR, Holzmann S, Wurm A, Pöch G (1979) Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary ... Diamond J, Janis RA (1978) Increases in cyclic GMP levels may not mediate relaxant effects of sodium nitroprusside, verapamil ... Schultz KD, Schultz K, Schultz G (1977) Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in ... Axelsson KL, Andersson RGG, Wikberg JES (1981) Correlation between vascular smooth muscle relaxation and increase in cyclic GMP ...
more infohttps://link.springer.com/article/10.1007/BF00508349

PLOS Pathogens: A Cyclic GMP Signalling Module That Regulates Gliding Motility in a Malaria ParasitePLOS Pathogens: A Cyclic GMP Signalling Module That Regulates Gliding Motility in a Malaria Parasite

... examined the effect of deleting candidate genes involved in controlling levels of the intracellular signalling molecule cyclic ...
more infohttps://journals.plos.org/plospathogens/article/related?id=10.1371/journal.ppat.1000599

Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis SynoviocytesCyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes

... Yan ... Yan Wang, Guo-Hua Su, Fang Zhang, Jing-Xue Chu, and Yun-Shan Wang, "Cyclic GMP-AMP Synthase Is Required for Cell Proliferation ...
more infohttps://www.hindawi.com/journals/mi/2015/192329/cta/

Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis SynoviocytesCyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether ... Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes. Yan ...
more infohttps://www.hindawi.com/journals/mi/2015/192329/abs/

Bibliographie: Regulation by cyclic di-GMP in Myxococcus xanthusBibliographie: Regulation by cyclic di-GMP in Myxococcus xanthus

Regulation by cyclic di-GMP in Myxococcus xanthus The nucleotide-based second messenger bis-(3-5)-cyclic dimeric GMP (c-di- ... GMP) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. ... Die Entdeckung des SgmT/DigR-Regulons und die Untersuchung der zellulären Rolle von c-di-GMP von: Petters, Tobias ...
more infohttp://archiv.ub.uni-marburg.de/ubfind/Record/urn:nbn:de:hebis:04-z2016-0101/Citations

Cyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August | 9780120329267 | BooktopiaCyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August | 9780120329267 | Booktopia

Buy a discounted Hardcover of Cyclic GMP online from Australias leading online bookstore. ... Booktopia has Cyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August. ... Cyclic GMP-dependent protein kinase. * Hormones and ligands that regulate GMP formation and/or metabolism. * Effects of cyclic ... cyclic GMP-dependent protein kinases, and various hormones and ligands that regulate cyclic GMP formation and/or metabolism. ...
more infohttps://www.booktopia.com.au/cyclic-gmp-j-thomas-august/prod9780120329267.html

Iron deficiency anemia in cyclic GMP kinase knockout mice | HaematologicaIron deficiency anemia in cyclic GMP kinase knockout mice | Haematologica

Iron deficiency anemia in cyclic GMP kinase knockout mice. Elisabeth Angermeier, Katrin Domes, Robert Lukowski, Jens ... Iron deficiency anemia in cyclic GMP kinase knockout mice. Elisabeth Angermeier, Katrin Domes, Robert Lukowski, Jens ... Mice with a global inactivation of the cyclic GMP kinase I (cGKI) gene (cGKI−/−) and mice that express cGKIα or cGKIβ in all ... Iron deficiency anemia in cyclic GMP kinase knockout mice Message Subject (Your Name) has forwarded a page to you from ...
more infohttp://www.haematologica.org/content/101/2/e48

Iron deficiency anemia in cyclic GMP kinase knockout mice | HaematologicaIron deficiency anemia in cyclic GMP kinase knockout mice | Haematologica

Iron deficiency anemia in cyclic GMP kinase knockout mice. Elisabeth Angermeier, Katrin Domes, Robert Lukowski, Jens ... Iron deficiency anemia in cyclic GMP kinase knockout mice. Elisabeth Angermeier, Katrin Domes, Robert Lukowski, Jens ... Mice with a global inactivation of the cyclic GMP kinase I (cGKI) gene (cGKI−/−) and mice that express cGKIα or cGKIβ in all ... Iron deficiency anemia in cyclic GMP kinase knockout mice Message Subject (Your Name) has forwarded a page to you from ...
more infohttp://www.haematologica.org/content/101/2/e48.long

Cyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts | Science SignalingCyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts | Science Signaling

Cyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts ... Cyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts ... Cyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts ... Cyclic GMP and Protein Kinase G Control a Src-Containing Mechanosome in Osteoblasts ...
more infohttps://stke.sciencemag.org/content/3/153/ra91

Pde11a - Dual 3,5-cyclic-AMP and -GMP phosphodiesterase 11A - Mus musculus (Mouse) - Pde11a gene & proteinPde11a - Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A - Mus musculus (Mouse) - Pde11a gene & protein

Catalyzes the hydrolysis of both cAMP and cGMP to 5-AMP and 5-GMP, respectively (By similarity). ... Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. ... Dual 3,5-cyclic-AMP and -GMP phosphodiesterase 11A (EC:3.1.4.35, EC:3.1.4.53). Alternative name(s): ... Dual 3,5-cyclic-AMP and -GMP phosphodiesterase 11AAdd BLAST. 933. ...
more infohttps://www.uniprot.org/uniprot/P0C1Q2

Expression and Genetic Activation of Cyclic Di-GMP-Specific Phosphodiesterases in Escherichia coli | Journal of BacteriologyExpression and Genetic Activation of Cyclic Di-GMP-Specific Phosphodiesterases in Escherichia coli | Journal of Bacteriology

The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous small signaling molecule which greatly affects bacterial ... Intracellular levels of the bacterial second messenger cyclic di-GMP (c-di-GMP) are controlled by antagonistic activities of ... 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-mediated signalling within the sigma network of Escherichia coli. Mol Microbiol 62:1014-1034. doi:10.1111/j.1365- ...
more infohttps://jb.asm.org/content/198/3/448

Human Metabolome Database: Showing metabocard for Cyclic GMP (HMDB0001314)Human Metabolome Database: Showing metabocard for Cyclic GMP (HMDB0001314)

Cyclic GMP. Description. Guanosine cyclic 3,5-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which ... Showing metabocard for Cyclic GMP (HMDB0001314). IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological properties ... Hunter KA, Singh GJ, Simpkins CO: Cyclic gmp is a measure of physiologic stress. J Natl Med Assoc. 2001 Jul-Aug;93(7-8):256-62 ... Sekhar, Konjeti R.; Grondin, Pascal; Francis, Sharron H.; Corbin, Jackie D. Design and synthesis of xanthines and cyclic GMP ...
more infohttp://www.hmdb.ca/metabolites/HMDB0001314

A Stable, Sensitive Fluorescence-based Method for Measuring Cyclic GMP | Molecular DevicesA Stable, Sensitive Fluorescence-based Method for Measuring Cyclic GMP | Molecular Devices

Secretion of cyclic GMP by cultured epithelial and fibroblast cell lines in response to nitric oxide. J. Pharm. Exp. Therap. ... Cyclic GMP calibrator. First assay performance was examined using the cGMP calibrator. Each concentration of cGMP calibrator ... Reagents. CatchPoint cyclic GMP fluorescent assay kit, including lyophilized cGMP calibrator, rabbit-anti-cGMP antibody, HRP- ... Cyclic GMP regulation and function in insects. Advances in Insect Physiol. In press. ...
more infohttps://www.moleculardevices.com/en/assets/app-note/reagents/stable-sensitive-fluorescence-based-method-for-measuring-cyclic-gmp

Evidence against direct involvement of cyclic GMP or cyclic AMP in bacterial chemotactic signaling. | Journal of BacteriologyEvidence against direct involvement of cyclic GMP or cyclic AMP in bacterial chemotactic signaling. | Journal of Bacteriology

Evidence against direct involvement of cyclic GMP or cyclic AMP in bacterial chemotactic signaling.. R C Tribhuwan, M S Johnson ... Defects in phosphotransferase chemotaxis in cya and cpd mutants previously cited as evidence of a cyclic GMP or cyclic AMP ... Phosphotransferase chemotaxis was normal in a cpd mutant of S. typhimurium that has elevated levels of cyclic GMP and cyclic ... Evidence against direct involvement of cyclic GMP or cyclic AMP in bacterial chemotactic signaling. ...
more infohttps://jb.asm.org/content/168/2/624?ijkey=e4a91c259ba30808ea21c9f31bb872fc9c800c88&keytype2=tf_ipsecsha

Cyclic GMP | BioVendorCyclic GMP | BioVendor

You are here: Home Products by Molecule of Interest Cyclic GMP Cyclic GMP. Guanosine 3, 5-cyclic monophosphate (cyclic GMP) ... Cyclic GMP High-Sensitivity Direct Chemiluminescent StressXpress® Immunoassay Kit Type: Competitive CLIA. ...
more infohttps://www.biovendor.com/cyclic-gmp

Light-regulated synthesis of cyclic-di-GMP by a bidomain construct of the cyanobacteriochrome Tlr0924 (SesA) without stable...Light-regulated synthesis of cyclic-di-GMP by a bidomain construct of the cyanobacteriochrome Tlr0924 (SesA) without stable...

Preparation of stable sup 125 I cyclic GMP tyrosine methyl ester suitable for 3,5 cyclic GMP radioimmunoassay by HPLC ... E88, a new cyclic-di-GMP class I riboswitch aptamer from Clostridium tetani, has a similar fold to the prototypical class I ... Title: Light-regulated synthesis of cyclic-di-GMP by a bidomain construct of the cyanobacteriochrome Tlr0924 (SesA) without ... Light-regulated synthesis of cyclic-di-GMP by a bidomain construct of the cyanobacteriochrome Tlr0924 (SesA) without stable ...
more infohttps://www.osti.gov/pages/biblio/1404947-light-regulated-synthesis-cyclic-di-gmp-bidomain-construct-cyanobacteriochrome-tlr0924-sesa-without-stable-dimerization
  • The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in Gluconacetobacter xylinus in order to produce microbial cellulose. (wikipedia.org)
  • In Gluconacetobacter xylinus, c-di-GMP stimulates the polymerization of glucose into cellulose as a high affinity allosteric activator of the enzyme cellulose synthase. (wikipedia.org)
  • The Gluconacetobacter xylinus cellulose synthase is allosterically stimulated by cyclic di-GMP, presenting a mechanism by which cyclic di-GMP can regulate cellulose synthase activity. (wikipedia.org)
  • This leads to the strong inference that conformational changes in PilZ domains allow the activity of targeted effector proteins (such as cellulose synthase) to be regulated by cyclic di-GMP. (wikipedia.org)
  • Cyclic GMP-AMP synthase (cGAS, cGAMP synthase), belonging to the nucleotidyltransferase family, is a cytosolic DNA sensor that activates the type-I interferon pathway. (wikipedia.org)
  • Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. (hindawi.com)
  • 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)
  • Intracellular pathogen resistance 1 ( Ipr1 ) has been found to be a mediator to integrate cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3), activated by intracellular pathogens, with the p53 pathway. (asm.org)
  • Bis-(3′-5′)-cyclic di-GMP (c-di-GMP), first identified as an allosteric activator of cellulose synthase in Gluconacetobacter xylinus ( 40 , 41 , 53 ), has been recognized as an important bacterial second messenger involved in the regulation of a number of processes. (asm.org)
  • Cyclic GMP-AMP synthase (cGAS) plays a central role in sensing aberrantly localized cytoplasmic dsDNA. (aacrjournals.org)
  • The Transcreener cGAMP cGAS Assay directly measures cyclic GMP-AMP (cGAMP) produced by cyclic GMP-AMP synthase (cGAS). (bellbrooklabs.com)
  • Although this protocol is generally applicable to a large number of various proteins complexed with DNA, we use cyclic G/AMP synthase (cGAS) enzyme as a case study for the protocol description. (elsevier.com)
  • The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. (helmholtz-hzi.de)
  • This signaling enzyme, The researchers explained, called cyclic GMP-AMP synthase (cGAS), exerting it's unique sensor effects in immune defense stream against the bacteria in general and tuberculosis bacteria in particular. (medcraveonline.com)
  • Angela CC, Haocheng C, Zhijian JC, Shiloh MU (2015) Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis. (medcraveonline.com)
  • Upon binding dsDNA, cGAS synthesizes the cyclic dinucleotide cGAMP, which acts as a second messenger to initiate a signaling pathway for the induction of interferon genes. (aacrjournals.org)
  • cGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity. (sasbdb.org)
  • Mice with a global inactivation of the cyclic GMP kinase I (cGKI) gene (cGKI −/− ) and mice that express cGKIα or cGKIβ in all smooth muscles on a cGKI −/− background 1 (cGKI RM mice) have a bleeding duodenal ulcer 2 and anemia of unknown cause. (haematologica.org)
  • The BLItz system was used to study binding between STING CBD (c-di-GMP binding domain) and IKK-like kinase TBK1. (moleculardevices.com)
  • The induction of type I interferons by the bacterial secondary messengers cyclic di-GMP (c-di-GMP) or cyclic di-AMP (c-di-AMP) is dependent on a signaling axis that involves the adaptor STING, the kinase TBK1 and the transcription factor IRF3. (sigmaaldrich.com)
  • We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. (ntu.edu.sg)
  • Cyclic GMP is the signal transducer of a family of transmembrane, particulate guanylyl cyclase (GC) receptors with key roles in physiology and disease. (embopress.org)
  • It is concluded that cyclic GMP does not determine the frequency of tumbling and is probably not a component of the transduction pathway. (asm.org)
  • In particular, the obtained findings define a novel c-di-GMP signaling pathway regulating the production of an unknown exopolysaccharide (EPS) and furthermore imply that local and global signaling pools potentially operate in B. subtilis to regulate motility and exopolysaccharide production. (uni-marburg.de)
  • The cytoplasmic DgcP synthetase can complement for DgcK only upon overproduction, while the third c-di-GMP synthetase, DgcW, seems not to be part of the signaling pathway. (uni-marburg.de)
  • a, HEK293T cells were transfected as indicated and cell lysates were subjected to an in-vitro UV-crosslinking assay with c-di-GMP 32 . (nih.gov)
  • b, HEK293T cells were transfected as in a and anti-HA immunoprecipitates were subjected to the c-di-GMP 32 binding assay or stained with Colloidal Blue. (nih.gov)
  • c and d, HEK293T cells were transfected as in a and cell lysates were UV-crosslinked to c-di-GMP 32 or GTP 32 in the presence of cold competing nucleotides in 10-fold serial dilutions beginning at 1 mM, except for guanosine (0.1 mM), VV 70mer (500 μg/mL), poly(dAT:dTA) (50 μg/mL) and poly(I:C) (50 μg/mL). (nih.gov)
  • This compound belongs to the class of organic compounds known as 3',5'-cyclic purine nucleotides. (hmdb.ca)
  • Cyclic dinucleotides have shown promise as novel vaccine adjuvants and immunotherapeutics, and our results provide insight into the mechanism by which cyclic dinucleotides are sensed by the innate immune system. (nih.gov)
  • In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. (wikipedia.org)
  • Recently, unique nucleic acids called cyclic dinucleotides, which function as conserved signalling molecules in bacteria, have also been shown to induce a STING-dependent type I IFN response. (nih.gov)
  • The nucleotide-based second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. (uni-marburg.de)
  • In particular, c-di-GMP controls important cellular and behavioral processes in a wide range of bacteria, including motility and chemotaxis, surface colonization and the formation of communities, virulence and persistence, and cell cycle progression (for reviews, see references 1 to 3 ). (asm.org)
  • Bacteria contain diverse c-di-GMP binding receptors/effectors, which exert the regulatory functions of this signaling molecule. (uni-marburg.de)
  • Furthermore, indications are provided within this study that all three DGCs might cooperate in inhibition of motility via the c-di-GMP receptor DgrA indicating that DgrA depends on globally elevated c-di-GMP levels. (uni-marburg.de)
  • Here we identified the heliase DDX41 as a pattern-recognition receptor (PRR) that sensed both c-di-GMP and c-di-AMP. (sigmaaldrich.com)
  • Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi. (semanticscholar.org)
  • Binding of DNA activates the enzyme to produce a unique cyclic dinucleotide second messenger, cGAMP, which acts as an agonist for the STING (stimulator of interferon genes) receptor, leading to induction of a type I interferon response. (bellbrooklabs.com)
  • Cyclic di-GMP levels regulate other processes via a number of mechanisms. (wikipedia.org)
  • Cyclic GMP has been proposed to regulate axonal development, but the molecular and cellular mechanisms underlying the formation of axon branches are not well understood. (jneurosci.org)
  • Temporal and/ or conditional separation through differential expression and activation of DGCs/ PDEs/ output systems respectively, could have a distinct impact on the global c-di-GMP pool. (uni-marburg.de)
  • Left) Several DGCs and PDEs can contribute to a common global pool of c-di-GMP (black dots). (asmscience.org)
  • We thus propose that PdeL acts both as an enzyme and as a c-di-GMP sensor to couple transcriptional activity to the c-di-GMP status of the cell. (asm.org)
  • After preincubation with cyclic AMP, the crr mutants were deficient in enzyme II glucose-mediated transport and chemotaxis, but other chemotactic responses were normal. (asm.org)
  • The wide range of different cellular processes and molecular targets that are regulated by c-di-GMP reflects its remarkable versatility as a signaling device. (asmscience.org)
  • Recognition of additional molecular targets in the areas of nitric oxide and cyclic GMP research will continue to promote drug discovery and development programs in the field. (biomedcentral.com)
  • Furthermore, we identify mutations in STING that selectively affect the response to cyclic dinucleotides without affecting the response to DNA. (nih.gov)
  • Although cyclic GMP and its 8-bromo derivative similarly inhibited these isoenzymes except PIII, they were considerably more effective against the hydrolysis of BCN than LN. (nus.edu.sg)
  • Since chromatography on PEI-cellulose efficiently resolves cyclic GMP, 5′-GMP, and guanosine, this methodology has also been adapted to the measurement of cyclic GMP hydrolysis. (elsevier.com)
  • Cumulatively, these results support a model of the V. cholerae life cycle in which c-di-GMP must be down-regulated early after entering the small intestine and maintained at a low level to allow virulence gene expression, colonization, and motility at appropriate stages of infection. (asm.org)
  • Diamond J, Janis RA (1978) Increases in cyclic GMP levels may not mediate relaxant effects of sodium nitroprusside, verapamil and hydralazine in rat vas deferens. (springer.com)
  • Does Cyclic GMP Mediate the Effects of Smooth Muscle Stimulants? (elsevier.com)
  • Thus, spatial separation of individual c-di-GMP signaling units was postulated. (asm.org)
  • Cyclic GMP signaling is important in many physiological responses including relaxation of smooth muscles, penile erection, kidney function and inflammatory responses1, 2, 3. (moleculardevices.com)
  • McDonald L G, Murad F. Nitric oxide and cyclic GMP signaling. (springer.com)
  • This work investigates the role of c-di-GMP and its players in the Gram-positive model organism B. subtilis, which possesses a relatively small c-di-GMP signaling equipment. (uni-marburg.de)
  • Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification. (diva-portal.org)
  • Global versus local c-di-GMP signaling modules. (asmscience.org)
  • Two possible architectures of c-di-GMP signaling modules are schematically depicted. (asmscience.org)
  • STING is a direct innate immune sensor of cyclic di-GMP. (nih.gov)
  • Here we report evidence that STING itself is an innate immune sensor of cyclic dinucleotides. (nih.gov)
  • Knockdown of DDX41 via short hairpin RNA in mouse or human cells inhibited the induction of genes encoding molecules involved in the innate immune response and resulted in defective activation of STING, TBK1 and IRF3 in response to c-di-GMP or c-di-AMP. (sigmaaldrich.com)
  • Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING. (helmholtz-hzi.de)
  • Recognition of cyclic‐di‐GMP by a riboswitch conducts translational repression through. (deepdyve.com)
  • In this study, we characterized structural changes of the Vc2 c‐di‐GMP riboswitch that represses translation of downstream open reading frames in a ligand‐dependent manner. (deepdyve.com)
  • Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions. (semanticscholar.org)
  • We established that WarA binds to cyclic-di-GMP, which potentiates its methyltransferase activity. (imperial.ac.uk)