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)
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.
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
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
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.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A 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.
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.
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.
A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
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.
That phase of a muscle twitch during which a muscle returns to a resting position.
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.
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
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.
Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
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.
The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.
A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.
An essential amino acid that is physiologically active in the L-form.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
A 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.
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
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)
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.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
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.
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.
The nonstriated involuntary muscle tissue of blood vessels.
The rate dynamics in chemical or physical systems.
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.
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.
Quinolines substituted in any position by one or more amino groups.
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)
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).
Drugs used to cause dilation of the blood vessels.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
A competitive inhibitor of nitric oxide synthetase.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.
A phosphodiesterase 4 inhibitor with antidepressant properties.
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.
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
A 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.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.
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)
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.
The conformation, properties, reaction processes, and the properties of the reactions of carbon compounds.
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.
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.
A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.
The main trunk of the systemic arteries.
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 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.
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.
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 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
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.
That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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.
Inosine 5'-(tetrahydrogen triphosphate). An inosine nucleotide containing three phosphate groups esterified to the sugar moiety. Synonym: IRPPP.
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.
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.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
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.
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)
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.-.
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 and EC EC 3.1.4.-.
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)
Compounds that specifically inhibit PHOSPHODIESTERASE 5.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
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.
A class of enzymes that catalyze oxidation-reduction reactions of amino acids.
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)
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.
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.
A group of compounds that are derivatives of beta-methylacetylcholine (methacholine).
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.
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.
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.
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.
An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.
Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.
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.
Inorganic salts of the hypothetical acid, H3Fe(CN)6.
Slender tubular or hairlike excretory structures found in insects. They emerge from the alimentary canal between the mesenteron (midgut) and the proctodeum (hindgut).
Compounds or factors that act on a specific enzyme to increase its activity.
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.
Purine bases found in body tissues and fluids and in some plants.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.
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.
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.
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).
The absence of light.
An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.
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.
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.
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)

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 - ...
On the stage of bacterial signal transduction and regulation, bis-(3-5)-cyclic dimeric guanosine monophosphate (c-di-GMP) has long played the part of Sleeping Beauty. c-di-GMP was first described in 1987, but only recently was it recognized that the enzymes that make and break it are not only ub …
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
Microorganisms can survive in challenging environments by rapidly adapting to the external conditions. Sensing external stimuli and transducing this information to the interior is in many cases mediated by phosphate signaling systems. Typical systems are composed of at least one sensor histidine kinase and one response regulator protein that communicate with each other via a phosphorylation cascade. In addition, Caulobacter and other bacteria use these systems to regulate their cell cycle. In such cases, not an external stimulus, but the fluctuating internal second messenger cyclic di-GMP is sensed. In close collaboration with the Jenal and the Schirmer labs, we use a combination of methods, in particular X-ray crystallography and NMR spectroscopy, to elucidate the underlying molecular mechanisms at the atomic level. We have shown that the activity of the histidine kinase CckA from the CckA-CtrA pathway involved in initiation of chromosome replication is regulated by cyclic di-GMP, we identified ...
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 ...
Nobelpreisträger Louis J. Ignarro (University of California, Los Angeles), 05.11.2019. The field of nitric oxide (NO) research has developed in explosive proportions since the discovery of endogenous NO in 1986. The first biologically important actions of NO were vasodilation and inhibition of blood clotting, by mechanisms involving stimulation of cyclic GMP production. The cyclic GMP system is the principal signal transduction mechanism by which NO elicits many of its physiological effects in mammals. NO acts as a CNS and peripheral neurotransmitter, where NO facilitates memory, learning, recall and erectile function. Based on these properties of NO, new drugs have been and are being developed to treat hypertension, atherosclerosis, stroke, angina pectoris, heart failure, vascular complications of diabetes, GI ulcers, impotency and other vascular disorders. The unique properties of NO allow for the opportunity to develop novel drugs for diagnosis, prevention and treatment of a multitude of ...
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. ...
Hussain, J.; Chen, J.; Locato, V.; Sabetta, W.; Behera, S.; Cimini, S.; Griggio, F.; Martínez-Jaime, S.; Graf, A.; Bouneb, M. et al.; Pachaiappan, R.; Fincato, P.; Blanco, E.; Costa, A.; De Gara, L.; Bellin, D.; Concetto de Pinto, M.; Vandelle, E.: Constitutive cyclic GMP accumulation in Arabidopsis thaliana compromises systemic acquired resistance induced by an avirulent pathogen by modulating local signals. Scientific Reports 6, 36423 (2016 ...
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 ...
/PRNewswire/ -- The Managing GMP Compliance and Phase Appropriate GMP Considerations for Virtual Companies conference has been added to...
GMP Labels help you comply with GMP, QSR & ISO requirements. Clearly identify various stages of your production, manufacturing and testing process.
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
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. - Nederland
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 Facility from European Collection of Cell Cultures (ECACC),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 ...
AASraw ontziratu gabeko produkziorako fabrikatzailea da (2701-50-0) CGMP araudiaren arabera, eta lineako salmentak eskaintzen ditu, kimiko sintetikoak eta pertsonalizatuak,
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, 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 aim of todays paper was to judge the relevance of neuronal balance of cyclic AMP and cyclic GMP concentration for functional regulation of nociceptor sensitivity during inflammation. the fact that hyperalgesic cytokines may activate soluble guanylate cyclase, which down-regulate the power of these chemicals to trigger hyperalgesia. This event shows up not to end up being mediated by prostaglandin or dopamine. To conclude, TWS119 the outcomes presented with this paper confirm a link between (i) hyperalgesia and raised degrees of cyclic AMP aswell as (ii) antinociception and raised degrees of cyclic GMP. The intracellular degrees of cyclic AMP that improve hyperalgesia are managed from the PDE4 isoform and appearance to bring about activation of proteins kinase A whereas the intracellular degrees of cyclic GMP outcomes from activation of the soluble guanylate cyclase. a syringe piston relocated by compressed air flow) to a location of 15?mm2 from the dorsal surface area from the hind paws of ...
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 ...
SILDENAFIL - sildenafil tablet, film coated - - - Sildenafil tablets are indicated for the treatment of erectile dysfunction. Consistent with its known effects on the nitric oxide/cGMP pathway [see Clinical Pharmacology (12.1, 12.2)] , sildenafil tablets were shown t
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 ...
TY - JOUR. T1 - Nucleotides function as endogenous chemical sensors for oxidative stress signaling. AU - Ihara, Hideshi. AU - Sawa, Tomohiro. AU - Nakabeppu, Yusaku. AU - Akaike, Takaaki. PY - 2011/1. Y1 - 2011/1. N2 - Oxidized and nitrated nucleotides including 8-oxogunanine and 8-nitroguanine derivatives such as 8-nitroguanosine 3′,5′-cyclic monophosphate were generated by reactive nitrogen oxides and reactive oxygen species in cultured cells and in tissues. 8-oxoguanine and 8-nitroguanine in DNA and RNA are potentially mutagenic, and the former also induces cell death. Some derivative, 8-nitroguanosine 3′,5′-cyclic monophosphate a major nitrated guanine nucleotide, was identified as a novel second messenger. Surprisingly, the amount of 8-nitroguanosine 3′,5′-cyclic monophosphate generated was found to be higher than that of guanosine 3′,5′-cyclic monophosphate in cells expressing inducible nitric oxide synthase. More important, 8-nitroguanosine 3′,5′-cyclic monophosphate ...
The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling appears to play a key role in inhibiting neuroinflammation and preventing the activation of a proapoptotic pathway, thereby promoting neural cell survival. In addition, evidence indicates that cGMP/protein kinase G (PKG) pathway is involved in the modulation of glial cell activity. Phosphodiesterase 5 (PDE5), which hydrolyzes cGMP in the inactive form, 5ʹGMP, is present throughout the body and brain and has emerged as a potential therapeutic target for diseases related to neuroinflammatory and neurodegenerative processes, since their inhibition leads to accumulation of cGMP. The objective of this chapter is to review current knowledge of NO/cGMP signaling pathways on neuroinflammation and the potential therapeutic use of PDE5 inhibitors (PDE5-Is) in neurological diseases. The extensive, while recent, literature on the effects of PDE-Is on Alzheimers disease (AD), multiple sclerosis (MS), Parkinsons disease (PD), Huntingtons disease
Guanosine-3ʹ-5ʹ-cyclic Monophosphate, 8-(4-Chlorophenylthio)-, Triethylammonium Salt - Calbiochem Selective membrane-permeable activator of protein kinase G that has a higher activation potential than cGMP. - Find MSDS or SDS, a COA, data sheets and more information.
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 ...
cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles lead to vasodilation and increased blood flow. cGMP is a secondary messenger in phototransduction in the eye. In the photoreceptors of the mammalian eye, the presence of light activates phosphodiesterase, which degrades cGMP. The sodium ion channels in photoreceptors are cGMP-gated, so degradation of cGMP causes sodium channels to close, which leads to the hyperpolarization of the photoreceptors plasma membrane and ultimately to visual information being sent to the brain.[2]. cGMP is also seen to mediate the switching on of the attraction of apical dendrites of pyramidal cells in cortical layer V towards semaphorin-3A (Sema3a).[3] Whereas the axons of pyramidal cells are repelled by Sema3a, the apical dendrites are attracted to it. The attraction is mediated by the increased levels of soluble guanylate ...
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 ...
Patients with minimal hepatic encephalopathy (MHE) show neurological impairment in specific tasks to which selective regional alterations in blood flow (BF) could contribute. Arterial spin labeling (ASL), a non-invasive magnetic resonance technique, quantitatively measures cerebral perfusion. We analyzed BF by ASL in different brain areas of controls and cirrhotic patients without and with MHE. We found that BF is more affected in cerebellum than in other areas of cirrhotic patients and that BF determination in cerebellum using ASL may detect MHE earlier than the Psychometric Hepatic Encephalopathy Score battery. Altered nitric oxide-cGMP pathway seems to be associated to altered BF in cerebellum ...
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 ...
3′,5′-Cyclic GMP spontaneously nonenzymatically polymerizes in a base-catalyzed reaction affording G oligonucleotides. When reacted with fully or partially sequence-complementary RNA (oligo C), the abiotically generated oligo G RNA displays a typical ribozyme activity consisting of terminal ligation accompanied by cleavage of an internal phosphate site of the donor oligonucleotide stem upon attack of the acceptor 3′ terminal OH. This reaction is dubbed Ligation following Intermolecular Cleavage (LIC). In a prebiotic perspective, the ability of oligo G polynucleotides to react with other sequences outlines a simple and possible evolutionary scenario based on the autocatalytic properties of RNA.
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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TY - JOUR. T1 - Host defense and oxidative stress signaling in bacterial infection AU - Akaike, Takaaki. PY - 2015. Y1 - 2015. N2 - Nitric oxide (NO) and reactive oxygen species (ROS) produced during infection are involved critically in host defense mechanisms. It is quite important to physiologically regulate ROS, such as superoxide, and NO. These reactive species produced in excess may cause oxidative damage of biological molecules. An important cytoprotective and antimicrobial function of NO and ROS is mediated by induction of heme oxygenase (HO)-1. The signaling mechanism of this HO-1 induction has remained unclear, however. We discovered in 2007 a unique second messenger, 8-nitroguanosine 3,5-cyclic monophosphate (8-nitro-cGMP), that mediates electrophilic signal transduction during oxidative stress and other cellular redox signaling in general. 8-Nitro-cGMP is formed via guanine nitration with NO and ROS, and in fact, NO-dependent 8-nitro-cGMP formation and HO-1 induction were identified ...
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
Over the past 25 years, the role of nitric oxide (NO) in biology has evolved from being recognized as an environmental pollutant to an endogenously produced substance involved in cell communication and signal transduction. NO is produced by a family of enzymes called nitric oxide synthases (NOSs), w …
23-c-di-AMP, a synthetic STING agonist, is a more potent immunostimulant in mammals than the natural bacterial cyclic dinucleotide 33-c-di-AMP. At low concentrations, the synthetic analog induces higher levels of type I IFNs than does c-di-AMP.
Vega Extra 120 Mg for the treatment of erectile dysfunction. Vega Extra 120 Mg is a reversible selective inhibitor of cyclic guanosine monophosphate (cGMP) PDE5.
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.
We are a GLP and GMP certified EU-located company providing testing specialized in molecular genetic based methods (NAT - nucleic acid tests). Our typical partners are general CROs outsourcing their DNA/RNA-based tests elsewhere. For (pre)clinical trials, we offer tailored analytical methods according to CROs´ demands. We also provide QC for batch release for pharma products as well (GMP testing).. Regarding biological drugs such as gene therapy compounds, biomolecules, vaccines, etc., GENERI BIOTECH covers all stages of development of a new drug - beginning with drug discovery via GLP preclinical testing phase up to later clinical tests.. When the development is successfully concluded, we provide DNA/RNA-based testing for the manufactured pharmaceutical cGMP.. ...
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 ...
Since January 2013 all imported APIs need to be accompanied by a so called Written Confirmation (except a few countries with equivalent GMP standards like the US and Switzerland) which should confirm that the manufacturing site is working under GMP (ICH Q7). But how much does the system help to improve quality of APIs. An investigation of written confirmations issued by the Indian Authorities reveals some surprises. Read more about the Written Confirmations for APIs.. ...
... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... Boerth NJ, Dey NB, Cornwell TL, Lincoln TM (1997). "Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell ... cyclic guanosine monophosphate (cGMP). In H 2S therapy immediately following an AMI, increased cGMP triggers an increase in ...
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 ...
Lei S, Jackson MF, Jia Z, Roder J, Bai D, Orser BA, MacDonald JF (June 2000). "Cyclic GMP-dependent feedback inhibition of AMPA ...
... 's function is related to two substances: cyclic AMP and cyclic GMP. They are derivatives of ATP and GTP, respectively, ... doi:10.1016/0014-2999(85)90283-3. Mattsson, Hillevi (1980). "Bicyclic phosphates increase the cyclic GMP level in rat ... GMP levels for all doses were relatively similar. They spiked after dosage, but each dose produced a similar sized spike. AMP ... Through testing a variety of doses of IPTBO on mice, researchers were able to study the corresponding effect on AMP and GMP ...
Cyclic GMP stimulates Ca2+ uptake by rod outer segments disks in such media. Transduction heats in retinal rods: tests of the ... George, J. S.; Hagins, W. A. (May 26, 1983). "Control of Ca2+ in rod outer segment disks by light and cyclic GMP". Nature. 303 ... Control of Ca2+ in rod outer segment disks by light and cyclic GMP - Experiments are performed to show the required Ca2+ ...
Example- Cobalamine biosynthesis, Cyclic AMP-GMP switch, lysin biosynthesis, glycine biosynthesis, fluroide switch etc. These ...
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). ... specifically by the cyclic-GMP-AMP synthase (cGAS). Upon DNA recognition, cGAS dimerizes and stimulates the formation of cyclic ... PDB: 4O6A​ Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ (February 2013). "Cyclic GMP-AMP is an endogenous second messenger ...
Pugh, E.N., Jr.; 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 ...
1975). "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic ... "Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea ... Wu AY, Tang XB, Martinez SE, Ikeda K, Beavo JA (September 2004). "Molecular determinants for cyclic nucleotide binding to the ... van Calker D, Müller M, Hamprecht B (1978). "Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells". Nature ...
... an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction". ...
... inhibition of cyclic AMP breakdown by cyclic GMP". Molecular Pharmacology. 37 (5): 671-681. Siess, Wolfgang; Eduardo, Lapetina ... In vivo phosphorylation of thromboxane by cyclic GMP-dependent protein kinase". Proceedings of the National Academy of Sciences ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). These signaling elements include ... 1990). "Functional relationship between cyclic AMP-dependent protein phosphorylation and platelet inhibition". Journal of ...
Kroll, S.; Phillips, W. J.; Cerione, R. A. (1989). "The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of ... cyclic GMP Phosphodiesterase. The Tα subunit of transducin contains three functional domains: one for rhodopsin/Tβγ interaction ... Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". ... Phosphodiesterase hydrolyzes cGMP to 5'-GMP. Decrease in cGMP concentration leads to decreased opening of cation channels and ...
... inhibition with BAY 73-6691 increases corpus cavernosum relaxations mediated by nitric oxide-cyclic GMP pathway in mice". ... thereby preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic ... 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi:10.1067/mai ... Fertel R, Weiss B (1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". Mol. ...
rpfG RNAs are located upstream of rpfG genes, which likely function as part of cyclic di-GMP signaling by degrading this ...
2006). "Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5 ... "Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle ...
These receptors generally function via intracellular second messengers, including cyclic AMP (cAMP), cyclic GMP (cGMP), ...
... which in turn activate many molecules of a cyclic GMP phosphodiesterase. Stryer's laboratory has also contributed to our ... "Flow of information in the light-triggered cyclic nucleotide cascade of vision". Proc. Natl. Acad. Sci. USA. 78 (1): 152-156. ...
... which changes the conformation of the opsin GPCR leading to signal transduction cascades which causes closure of cyclic GMP- ... PDE hydrolyzes cGMP, forming GMP. This lowers the intracellular concentration of cGMP and therefore the sodium channels close. ... stopping the transformation of cGMP to GMP. This deactivation step of the phototransduction cascade (the deactivation of the G ...
... an enzyme catalysing the synthesis of cyclic-GMP from GTP Neisseria gonorrhoeae or gonococcus, the causative agent of gonorrhea ...
... donating various elements towards the building of the ring GMP can also exist as a cyclic structure known as cyclic GMP. Within ... GMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase guanine; hence it is a ribonucleoside ... Guanosine monophosphate (GMP), also known as 5′-guanidylic acid or guanylic acid (conjugate base guanylate), is a nucleotide ... As an acyl substituent, it takes the form of the prefix guanylyl-. GMP synthesis starts with D-ribose 5′-phosphate, a product ...
... on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora ... Advances in Cyclic Nucleotide Research. 5. pp. 195-211. ISBN 978-0-89004-021-8. PMID 165666. Fertel R, Weiss B (July 1976). " ... Uzunov P, Weiss B (September 1972). "Separation of multiple molecular forms of cyclic adenosine-3',5'-monophosphate ... There, NO activates soluble guanylate cyclase which converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate ( ...
... cyclic GMP-AMP synthase EC diacylglycerol ethanolaminephosphotransferase EC diacylglycerol ...
The breakdown results in the activation of Transducin and this activates cyclic GMP Phosphodiesterase, which lowers the number ... of open Cyclic nucleotide-gated ion channels on the cell membrane, which leads to hyperpolarization; this hyperpolarization of ...
... cyclic cmp MeSH D13.695.462.275 - cyclic gmp MeSH D13.695.462.275.325 - dibutyryl cyclic gmp MeSH D13.695.462.300 - cyclic imp ... cyclic gmp MeSH D13.695.827.426.160.325 - dibutyryl cyclic gmp MeSH D13.695.827.426.340 - guanosine diphosphate MeSH D13.695. ... cyclic gmp MeSH D13.695.667.454.160.325 - dibutyryl cyclic gmp MeSH D13.695.667.454.200 - deoxyguanine nucleotides MeSH D13.695 ... cyclic amp MeSH D13.695.462.200.225 - 8-bromo cyclic adenosine monophosphate MeSH D13.695.462.200.250 - bucladesine MeSH ...
... cyclic gmp-dependent protein kinases MeSH D12.644.360.200.575 - protamine kinase MeSH D12.644.360.250 - cyclin-dependent ... cyclic nucleotide-regulated protein kinases MeSH D12.644.360.200.125 - cyclic amp-dependent protein kinases MeSH D12.644. ...
... 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 ...
... (cyclic GMP-AMP, cGAMP) is the first cyclic di-nucleotide found in ... May 3, 2013). "Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase ... 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 ...
... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ... interacts with the delta subunit of rod cyclic GMP phosphodiesterase". Proceedings of the National Academy of Sciences of the ...
1975). "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic ... "Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea ... van Calker D, Müller M, Hamprecht B (1978). "Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells". Nature ... this glutamine is constrained by neighboring residues to a position favoring selectivity for either cyclic nucleotide.[1] (See ...
Lolley RN, Lee RH (September 1990). "Cyclic GMP and photoreceptor function". The FASEB Journal : Official Publication of the ... "Cyclic Nucleotide-Regulated Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... "Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels". Nature 452 (7190): 1007- ...
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 ...
環狀(英語:Cyclic nucleotide). *cAMP. *cGMP. *c-di-GMP(英語:Cyclic di-GMP) ...
Fertel R, Weiss B (1976). „Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" (abstract). ... aktivnost 3',5'-ciklične-GMP fosfodiesteraze. Celularna komponenta. • celularna komponenta. Biološki proces. • prenos signala. ... Weiss B (1975). „Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv ... Weiss B, Hait WN (1977). „Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annu. Rev ...
... since both NO and PDE5 inhibitors increase cyclic GMP levels and the sum of their pharmacodynamic effects will greatly exceed ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ...
Cyclic nucleotide. *cAMP. *cGMP. *c-di-GMP. *c-di-AMP. *cADPR. Nucleoside diphosphate. ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ...
Roskoski R, Roskoski LM (Jan 1987). "Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second ... response to organic cyclic compound. • eating behavior. • cellular response to growth factor stimulus. • heart morphogenesis. • ... "Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation" ...
... can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosphate (cGMP), guanosine ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... An example is adenylate cyclase, which produces the second messenger cyclic AMP.[6] For this discovery, they won the 1994 Nobel ... which produces the second messenger cyclic AMP.[6] ...
cGMP; 3',5'-cyclic GMP; Guanosine cyclic monophosphate; Cyclic 3',5'-GMP; Guanosine 3',5'-cyclic phosphate ... Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are cGMP ... Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second ... Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Guanylate cyclase catalyzes the reaction of guanosine triphosphate (GTP) to 3',5'-cyclic guanosine monophosphate (cGMP) and ... Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ...
... inhibition with BAY 73-6691 increases corpus cavernosum relaxations mediated by nitric oxide-cyclic GMP pathway in mice". ... Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ...
2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID ... AMP (cAMP) • UMP • GMP (cGMP) • CMP • ADP • UDP (m5UDP) • GDP • CDP • ATP • UTP • GTP • CTP ...
Yeast tRNA cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3' end. Yeast tRNA ... 3'OH of a free guanine nucleoside (or one located in the intron) or a nucleotide cofactor (GMP, GDP, GTP) attacks phosphate at ... cyclic phosphodiester group, and a 3'-half tRNA, terminating at a 5'-hydroxyl group, along with a discarded intron.[20] Yeast ...
Essayan DM (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671-80. doi:10.1067/mai.2001.119555 ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. CiteSeerX ... catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP).[8] Increases in concentration of the second ...
1996): Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile ... Den hæmmer omdannelsen af det vasodilatoriske cGMP til GMP. Derved stiger niveauet af cGMP, der via PKG virker vasodilatorisk. ...
cellular response to organic cyclic compound. • viral process. • response to iron ion. • regulation of gene expression. • ...
Pugh Jr, E. N.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate ...
Cyclic. cAMP, cGMP, c-di-GMP, cADPR. जैवरासायनिक परिवार: कार्बोहाइड्रेट (ग्लाइकोसाइड, अल्कोहॉल) · लिपिड (Steroids, ... monophosphates (AMP, GMP, UMP, CMP) · diphosphates (ADP, GDP, UDP, CDP) · triphosphates (ATP, GTP, TTP, UTP, CTP) ...
... an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction". Int ... Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in ...
Cyclic nucleotide. *cAMP. *cGMP. *c-di-GMP. *cADPR. Nucleoside diphosphate. *ADP. *GDP ...
While studying cyclic GMP, Ignarro read a paper by Ferid Murad, who demonstrated that nitric oxide elevates cyclic GMP levels. ... Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. ... CIBA Award for Hypertension Research for Discovery of the Roles of Nitric Oxide and Cyclic GMP in Vascular Function. Shared ... Tulane was chosen partially because it would provide a good environment for continued research into cyclic GMP. ...
2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID ... Theobromine is weaker in both its inhibition of cyclic nucleotide phosphodiesterases and its antagonism of adenosine receptors. ...
2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID ...
... 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 ...
VieA controls the intracellular concentration of the cyclic nucleotide second messenger cyclic diguanylate (c-di-GMP) using an ... Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation Mol Microbiol. 2004 Aug;53(3):857-69. doi: 10.1111/j. ... Expression of unrelated V. cholerae c-di-GMP synthetase or phosphodiesterae proteins also modulated c-di-GMP concentration and ... Two-dimensional thin layer chromatography of nucleotide extracts confirmed that VieA reduces the concentration of c-di-GMP, ...
... 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 ...
Discovery of cyclic AMP-GMP-sensing riboswitches. Colleen A. Kellenberger, Stephen C. Wilson, Scott F. Hickey, Tania L. ... Discovery of cyclic AMP-GMP-sensing riboswitches. Colleen A. Kellenberger, Stephen C. Wilson, Scott F. Hickey, Tania L. ... A synthase for cyclic AMP-GMP (cAG, also referenced as 3′-5′, 3′-5′ cGAMP) called DncV is associated with hyperinfectivity of ... GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP. Colleen A. Kellenberger, Stephen C. ...
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 ...
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, ...
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 ...
NO, nitrotyrosine, and cyclic GMP in signal transduction Med Sci Monit. Jul-Aug 2001;7(4):801-19. ... Activation of sGC results in the production of 3,5-cyclic guanosine monophosphate (cGMP), an intracellular second messenger ...
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. ...
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 ...
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 ...
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 ...
... examined the effect of deleting candidate genes involved in controlling levels of the intracellular signalling molecule cyclic ...
... Yan ... Yan Wang, Guo-Hua Su, Fang Zhang, Jing-Xue Chu, and Yun-Shan Wang, "Cyclic GMP-AMP Synthase Is Required for Cell Proliferation ...
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 ...
Defining Specificity Determinants of Cyclic GMP-Mediated Gustatory Sensory Transduction in Caenorhabditis elegans. Heidi K. ...
Cyclic GMP spontaneously nonenzymatically polymerizes in a base-catalyzed reaction affording G oligonucleotides. When reacted ... 2.2.1. Polymerization of 3′,5′-cyclic GMP. Polymerization of 3′,5′-cyclic GMP was performed as described in the literature [16, ... Cyclic GMP by Samanta Pino 1, Giovanna Costanzo 2, Alessandra Giorgi 3, Jiří Šponer 4, Judit E. Šponer 4 and Ernesto Di Mauro 1 ... 3′,5′-Cyclic GMP spontaneously nonenzymatically polymerizes in a base-catalyzed reaction affording G oligonucleotides. When ...
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 ...
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. ...
"Retraction: Regulation of FoxO1 Transcription Factor by Nitric Oxide and Cyclic GMP in Cultured Rat Granulosa Cells," ... Retraction: Regulation of FoxO1 Transcription Factor by Nitric Oxide and Cyclic GMP in Cultured Rat Granulosa Cells. ... "Retraction: Regulation of FoxO1 Transcription Factor by Nitric Oxide and Cyclic GMP in Cultured Rat Granulosa Cells," ...
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 ...
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 ...
Bis-(3′-5′)-cyclic di-GMP (c-di-GMP) is a universal bacterial secondary messenger and a key player in the decision between the ... High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached ... Immobilization of c-di-GMP on Sepharose 6B.c-di-GMP was synthesized as previously specified (40). Preparation of c-di-GMP ... Application of Synthetic Peptide Arrays To Uncover Cyclic Di-GMP Binding Motifs. Juliane Düvel, Sarina Bense, Stefan Möller, ...
Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays ... Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays ... Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING ...
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:, EC: Alternative name(s): ... Dual 3,5-cyclic-AMP and -GMP phosphodiesterase 11AAdd BLAST. 933. ...
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- ...
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 ...
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. ...
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. ...
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 ...
  • Other Wnts exert their influences in other ways, such as increasing intracellular concentrations of Ca 2 + and decreasing intracellular concentrations of cyclic guanosine monophosphate (cGMP). (
  • Activation of sGC results in the production of 3',5'-cyclic guanosine monophosphate (cGMP), an intracellular second messenger signaling molecule, which can subsequently mediate such diverse physiological events such as vasodilatation and immunomodulation. (
  • An important target of NO is the soluble guanylyl cyclase (sGC) that generates the second messenger cyclic guanosine-3′-5′-monophosphate (cGMP) ( 19 ). (
  • The dissolution of cyclic purine nucleotides (markedly of 3′,5′-cGMP) in water results in the formation of oligonucleotides by their spontaneous nonenzymatic polymerization [ 16 , 17 ]. (
  • Mechanical stimulation is crucial for bone growth and remodeling, and fluid shear stress promotes anabolic responses in osteoblasts through multiple second messengers, including nitric oxide (NO). NO triggers production of cyclic guanosine 3′,5′-monophosphate (cGMP), which in turn activates protein kinase G (PKG). (
  • Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. (
  • Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively (By similarity). (
  • 3´, 5´ cyclic guanosine monophosphate (cGMP) is a secondary messenger in signal transduction pathways that is produced by the enzyme guanylyl cyclase (GC). (
  • The pathway involving the cyclic guanosine-3′,5′-monophosphate (cGMP) may provide a unique signaling mechanism in regulating axon branching. (
  • Effects OF Sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. (
  • 2,3 Cyclic GMP is degraded by cGMP-hydrolyzing phosphodiesterases (PDEs). (
  • 6 Like NO, cGMP can affect multiple signaling pathways ( Figure 1 A). 1,5,6 To date, three classes of cGMP receptor proteins have been identified: cyclic nucleotide-gated (CNG) cation channels, cGMP-regulated PDEs, which hydrolyze cAMP and/or cGMP, and cGMP-dependent protein kinases (cGKs). (
  • We found that sulindac sulfone and two potent derivatives, CP248 and CP461, inhibited the cyclic GMP (cGMP) phosphodiesterases (PDE) 2 and 5 in human colon cells, and these compounds caused rapid and sustained activation of the c-Jun NH 2 -terminal kinase 1 (JNK1). (
  • 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. (
  • We investigated the effect of the soluble guanylate cyclase inhibitor methylene blue and the cGMP-dependent protein kinase (PKG) inhibitor 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate, Rp isomer, on inhibition by SNP or CNP. (
  • 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. (
  • Mouse Direct Cyclic GMP (cGMP) Chemiluminescent Immunoassay kits will measure cGMP present in lysed cells, EDTA plasma, urine, saliva and culture media samples. (
  • We hypothesised that pharmacological treatment of human skeletal muscle with N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) would increase intracellular cyclic GMP (cGMP) levels and promote glucose transport.METHODS: Skeletal muscle strips were prepared from vastus lateralis muscle biopsies obtained from seven healthy men. (
  • Cyclic GMP (cGMP) is the intracellular messenger that mediates phototransduction in retinal rods. (
  • Besides soluble guanylyl cyclase (sGC, the receptor for nitric oxide), seven transmembrane guanylyl cyclase (GC) receptors synthesize the second‐messenger cyclic GMP (cGMP) (Kuhn, 2003 ). (
  • GAF domains are ubiquitous motifs present in cyclic GMP (cGMP)‐regulated cyclic nucleotide phosphodiesterases, certain adenylyl cyclases, the bacterial transcription factor FhlA, and hundreds of other signaling and sensory proteins from all three kingdoms of life. (
  • The structural and binding studies taken together show that the cGMP binding GAF domains form a new class of cyclic nucleotide receptors distinct from the regulatory domains of cyclic nucleotide‐regulated protein kinases and ion channels. (
  • Not only are they allosterically regulated by cGMP at non‐catalytic sites, they also hydrolyze cGMP to 5′‐GMP. (
  • A gene on chromosome 11q15.1 that encodes a cyclic nucleotide phosphodiesterase, which plays a critical role in signal transduction, regulating intracellular cyclic nucleotide concentrations by hydrolysing second messengers cAMP and/or cGMP to AMP and GMP, and in turn regulating physiological processes. (
  • The long-term goal is to determine the molecular mechanisms that regulate synthesis of a second messenger of phototransduction, cyclic GMP (cGMP), by retinal membrane guanylyl cyclases (retGC). (
  • The Cyclic GMP EIA Kit is designed to quantitatively measure cGMP present in lysed cells, EDTA plasma, urine, saliva and tissue culture media samples. (
  • Cyclic GMP (cGMP) has been implicated in modulating the effects of general anaesthesia. (
  • To sustain a cGMP flux that is severalfold greater than that in the dark-adapted state, continuous illumination must activate the entire cGMP metabolic cycle, which consists of phosphodiesterase, guanylyl cyclase, and the enzymes phosphorylating GMP and GDP. (
  • 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. (
  • In Gluconacetobacter xylinus, c-di-GMP stimulates the polymerization of glucose into cellulose as a high affinity allosteric activator of the enzyme cellulose synthase. (
  • 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. (
  • 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. (
  • A synthase for cyclic AMP-GMP (cAG, also referenced as 3′-5′, 3′-5′ cGAMP) called DncV is associated with hyperinfectivity of Vibrio cholerae but has not been found in many bacteria, raising questions about the prevalence and function of cAG signaling. (
  • Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. (
  • 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). (
  • Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). (
  • To date, several DNA sensors that activate the canonical STING/TBK-1/IRF3 signaling axis have been proposed, including IFI16 ( 4 - 6 ) and, most recently, the DNA sensor cyclic GMP-AMP synthase (cGAS) ( 15 - 18 ). (
  • 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. (
  • 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. (
  • The Transcreener cGAMP cGAS Assay directly measures cyclic GMP-AMP (cGAMP) produced by cyclic GMP-AMP synthase (cGAS). (
  • 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. (
  • In mammalian cells, cGAMP is synthesized by cyclic GMP-AMP synthase (cGAS) from ATP and GTP upon cytosolic DNA stimulation. (
  • The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. (
  • 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. (
  • Angela CC, Haocheng C, Zhijian JC, Shiloh MU (2015) Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis. (
  • Intracellular levels of the bacterial second messenger cyclic di-GMP (c-di-GMP) are controlled by antagonistic activities of diguanylate cyclases and phosphodiesterases. (
  • Thus, all of these proteins are bona fide phosphodiesterases that are capable of interfering with different c-di-GMP-responsive output systems by affecting the global c-di-GMP pool. (
  • We demonstrate that a subset of E. coli phosphodiesterases can be activated genetically to affect the global c-di-GMP pool and thus influence different c-di-GMP-dependent processes. (
  • The key enzymes involved in c-di-GMP metabolism are diguanylate cyclases (DGCs) ( 4 ) and phosphodiesterases (PDEs) ( 5 ). (
  • Francis S H, Turko I V, Corbin J D. Cyclic nucleotide phosphodiesterases: relating structure and function. (
  • c-di-GMP homeostasis is carried out by GGDEF domain proteins, cyclic diguanylate cyclases (DGCs), which synthesize c-di-GMP, as well as EAL and HD-GYP domain proteins, c-di-GMP phosphodiesterases (PDEs), which degrade this nucleotide. (
  • Intracellular c-di-GMP levels are controlled by the antagonistic activity of c-di-GMP specific synthetases (diguanylate cyclases, DGCs) and hydrolases (phosphodiesterases, PDEs). (
  • Inhibition of cyclic GMP-dependent phosphodiesterases 2 and 5 leads to cellular cyclic GMP accumulation and subsequent activation of cyclic GMP-dependent protein kinase (PKG). (
  • In turn, c-di-GMP is hydrolyzed by EAL domain phosphodiesterases (PDEs), including VieA, which is described below ( 9 , 10 , 45 , 48 ). (
  • Rubin, Charles S. / Rapid assay for cyclic AMP and cyclic GMP phosphodiesterases . (
  • The cyclic GMP phosphodiesterase was separated from cyclic AMP phosphodiesterases by column chromatography on hydroxyapatite and Sephadex G-200. (
  • cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. (
  • cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP. (
  • The PilZ domain has been shown to bind cyclic di-GMP and is believed to be involved in cyclic di-GMP-dependent regulation, but the mechanism by which it does this is unknown. (
  • Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin. (
  • To approach the potential regulation of exopolysaccharide production through c-di-GMP via YdaK, different combinations of overexpression and deletion mutants of the operon and of dgc genes, respectively, were generated. (
  • The molecular and cellular mechanisms that underlie the characteristic behavior of Caulobacter cells and its regulation by c-di-GMP might thus be of general relevance for the understanding of processes involved in the motile-sessile transition in many other bacteria. (
  • Endothelial regulation of cyclic GMP and vascular responses in. (
  • Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. (
  • Our studies further suggest that the regulation of chemotaxis by c-di-GMP through MapZ orthologs/homologs is widespread in proteobacteria and that the use of allosterically regulated C-terminal motifs could be a common mechanism for PilZ adaptor proteins. (
  • Information on cyclic nucleotide regulation and signal transduction. (
  • These diverse effects of nitric oxide that are cyclic GMP dependent or independent can alter and regulate numerous important physiological events in cell regulation and function. (
  • Fingerprint Dive into the research topics of 'Regulation of cyclic GMP metabolism in toad photoreceptors. (
  • Cyclic di-GMP (also called cyclic diguanylate and c-di-GMP) is a second messenger used in signal transduction in a wide variety of bacteria. (
  • less thanbrgreater than less thanbrgreater thanThe findings give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together in regulating muscle tension in the transition zone. (
  • In particular, genome sequence information of the pathogen Xanthomonas campestris pathovar campestris has allowed researchers to identify and functionally analyze the role of intracellular signaling involving cyclic di-GMP in black rot disease of crucifers. (
  • We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING. (
  • The bacterial second messenger cyclic di-guanosine monophosphate controls a wide variety of cellular functions by acting on a riboswitch motif in numerous messenger RNAs. (
  • Gruetter CA, Gruetter DY, Lyon JE, Kadowitz PJ, Ignarro LJ (1981) Relationship between cyclic guanosine 3′:5′-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: Effects of methylene blue and methemoglobin. (
  • Guanosine 3', 5'-cyclic monophosphate (cyclic GMP) is a second messenger that is typically present in lower level than cAMP. (
  • Cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, cGAMP) is the first cyclic di-nucleotide found in metazoa. (
  • Bis-(3',5')-cyclic dimeric adenosine monophosphate: strong Th1/Th2/Th17 promoting mucosal adjuvant. (
  • MPYS/STING-mediated TNF-α, not type I IFN, is essential for the mucosal adjuvant activity of (3'-5')-cyclic-di-guanosine-monophosphate in vivo. (
  • Nitrate, a breakdown product of peroxynitrite (ONOO − ), was substantially increased in parallel with a decline in cyclic guanosine monophosphate (GMP). (
  • The protein S-modulin (M(r) 26,000) is known to increase the fraction of light-activated cyclic GMP-phosphodiesterase (PDE) at high Ca2+ concentrations in frog rod photoreceptors. (
  • Chapters include discussions on the guanylyl cyclase and phosphodiesterase isoenzyme families for cyclic GMP synthesis and hydrolysis, cyclic GMP-dependent protein kinases, and various hormones and ligands that regulate cyclic GMP formation and/or metabolism. (
  • In this study, we used peptide arrays to uncover the c-di-GMP binding site of a Pseudomonas aeruginosa protein (PA3740) that was isolated in a chemical proteomics approach. (
  • Those three amino acids are highly conserved across PA3740 homologs, and their singular exchange to alanine reduced c-di-GMP binding within the full-length protein. (
  • less thanbrgreater than less thanbrgreater thanIn the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKI alpha, and cGKI, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. (
  • We designed duplex siRNA constructs to target GC-A, VASP, and cyclic GMP-dependent protein kinase (PKG). (
  • We have created cyclic di-GMP level reporters by transcriptionally fusing the cyclic di-GMP-responsive cdrA promoter to genes encoding green fluorescent protein. (
  • The Degenerate EAL-GGDEF Domain Protein Filp Functions as a Cyclic di-GMP Receptor and Specifically Interacts with the PilZ-Domain Protein PXO_02715 to Regulate Virulence in Xanthomonas oryzae pv. (
  • We show here that K-Ras is a substrate for cyclic GMP-dependent protein kinases (PKGs). (
  • When levels of cyclic-di-GMP are high, cyclic-di-GMP binds to a protein called LapD, which can then in turn bind to an enzyme known as LapG. (
  • Effect of cyclic GMP-increasing agents nitric oxide and C-type natriuretic peptide on bovine chromaffin cell function: inhibitory role mediated by cyclic GMP-dependent protein kinase. (
  • Biosynthesis and degradation of c-di-GMP are performed by three protein domains. (
  • Recent evidence shows that the protein domain HD-GYP can also degrade c-di-GMP ( 42 ). (
  • We report here that the cyclic GMP-inhibited cyclic AMP specific phosphodiesterase (PDE3B) is expressed as a membrane-bound protein in clonal insulin-secreting BRIN-BD11 cells. (
  • Analysis of the Borrelia burgdorferi cyclic-di-GMP-binding protein PlzA reveals a role in motility and virulence. (
  • 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. (
  • 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. (
  • We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. (
  • The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein. (
  • This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. (
  • Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. (
  • c-di-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. (
  • Here, we present the structure of the PilZ adaptor protein MapZ cocrystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa. (
  • Together, the findings provide detailed structural insights into how c-di-GMP controls the activity of an enzyme target indirectly through a PilZ adaptor protein. (
  • Cyclic GMP, in turn, can activate cyclic GMP-dependent protein kinase (PKG) and can cause smooth muscles and blood vessels to relax, decrease platelet aggregation, alter neuron function, etc. (
  • Murad F. Cyclic GMP: synthesis, metabolism, and function. (
  • The proposed c-di-GMP receptor YdaK resides in the putative EPS synthesis operon ydaJKLMN. (
  • Waldman SA, Murad F. Cyclic GMP synthesis and function. (
  • In many instances, nitric oxide mediates its biological effects by activating the soluble isoform of guanylyl cyclase and increasing cyclic GMP synthesis from GTP. (
  • We were interested to find out whether Mycobacterium smegmatis strains lacking the gene for either (p)ppGpp synthesis (Delta rel(Msm)) or c-di-GMP synthesis (Delta dcpA) would display similar phenotypes. (
  • Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. (
  • abstract = "A rapid highly sensitive assay for cyclic AMP phosphodiesterase has been devised. (
  • High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached growth in many bacteria. (
  • IMPORTANCE In many bacterial pathogens the universal bacterial second messenger c-di-GMP governs the switch from the planktonic, motile mode of growth to the sessile, biofilm mode of growth. (
  • The bacterial second messenger c-di-GMP represents an integral key regulator in the control of bacterial motility and biofilm formation. (
  • Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. (
  • The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility, and pathogenicity. (
  • Degenerate GGDEF and EAL domain proteins represent major types of cyclic diguanylic acid (c-di-GMP) receptors in pathogenic bacteria. (
  • Endoh M, Yamashita S, Taira N (1982) Positive inotropic effect of amrinone in relation to cyclic nucleotide metabolism in the canine ventricular muscle. (
  • Cyclic GMP metabolism and its role in brain physiology. (
  • Cyclic GMP metabolism and its role in brain physiology " (2005) J Physiol Pharmacol 56 Suppl 2, 15-34. (
  • Altogether, our data suggest that (p)ppGpp and c-di-GMP may be involved in the metabolism of glycopeptidolipids and polar lipids in M. smegmatis. (
  • Cyclic di-GMP is synthesized by proteins with diguanylate cyclase activity. (
  • Degradation of cyclic di-GMP is affected by proteins with phosphodiesterase activity. (
  • Two-dimensional thin layer chromatography of nucleotide extracts confirmed that VieA reduces the concentration of c-di-GMP, opposing the action of c-di-GMP synthetase proteins. (
  • Expression of unrelated V. cholerae c-di-GMP synthetase or phosphodiesterae proteins also modulated c-di-GMP concentration and vps gene expression. (
  • We propose that c-di-GMP synthetase and phosphodiesterase domain-containing proteins contribute to regulating biofilm formation by controlling c-di-GMP concentration. (
  • A group of enzymes that are dependent on cyclic GMP and catalyzes the phosphorylation of serine or threonine residues of proteins. (
  • Not only can c-di-GMP bind to nucleic acids and directly control gene expression, but it also binds to a diverse array of proteins of specialized functions and orchestrates their activity. (
  • Different c-di-GMP effector proteins (A, B, and C) can bind c-di-GMP with different affinities and by that can stage a graded response as levels of the second messenger fluctuate. (
  • Right) Temporally or spatially separated c-di-GMP signaling modules regulate specific cellular processes by exclusive interaction with one or several effector proteins. (
  • Cyclic-di-GMP affects the stability of the biofilm via a group of proteins called the Lap system. (
  • As cyclic-di-GMP-unbound LapD proteins interact poorly with LapG, this leaves some LapG molecules able to destabilize the attachments between the cells and the surface, which disperses the biofilm. (
  • Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. (
  • Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. (
  • Guanylyl cyclases and signaling by cyclic GMP " (2000) Pharmacol Rev 52: 375-414. (
  • Cyclic GMP is the signal transducer of a family of transmembrane, particulate guanylyl cyclase (GC) receptors with key roles in physiology and disease. (
  • 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. (
  • 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. (
  • Most interestingly, different from the previously identified c-di-GMP binding motif of the PilZ domain (RXXXR) or the I site of diguanylate cyclases (RXXD), two leucine residues and a glutamine residue and not the charged amino acids provided the key residues of the binding sequence. (
  • Diguanylate cyclases (DGCs) containing a GGDEF domain, named for conserved residues, synthesize c-di-GMP from two GTPs ( 4 , 36 , 43 ). (
  • 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. (
  • Here we identified the heliase DDX41 as a pattern-recognition receptor (PRR) that sensed both c-di-GMP and c-di-AMP. (
  • Thus, we concluded that Filp was a novel c-di-GMP receptor of X. oryzae pv. (
  • High cytoplasmic levels of cyclic-di-GMP activate the transmembrane receptor LapD that in turn recruits the periplasmic protease LapG, preventing it from cleaving a cell surface-bound adhesin, thereby promoting cell adhesion. (
  • Given the conservation of key elements of this receptor system in many bacterial species, the results are broadly relevant for cyclic-di-GMP- and HAMP domain-regulated transmembrane signaling. (
  • Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi. (
  • 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. (
  • Pirenzepine selectively antagonized muscarinic receptor-mediated cyclic GMP formation in a noncompetitive fashion in mouse neuroblastoma cells (clone N1E-115). (
  • Thus, antagonistic modulation of I Ca(L) by cyclic nucleotides could be referable to phosphorylation of different regulatory sites on the α 1c subunit. (
  • Processes that are known to be regulated by cyclic di-GMP, at least in some organisms, include biofilm formation, motility and virulence factor production. (
  • In general, increased levels of cyclic di-GMP (c-di-GMP) inside bacterial cells correlate with biofilm formation and expression of exopolysaccharide (EPS) and adherence factors, while decreased intracellular levels stimulate motility and a planktonic lifestyle. (
  • The second messenger cyclic di-GMP is a positive regulator of biofilm formation, and cyclic di-GMP signaling is now regarded as a potential target for the development of antipathogenic compounds. (
  • The decision to shift between a free-swimming and a biofilm life-style is orchestrated by a signaling molecule found inside the bacteria called cyclic-di-GMP. (
  • If not enough phosphate is available, the level of cyclic-di-GMP falls and the biofilm disperses. (
  • In Vibrio cholerae , the second messenger cyclic di-GMP (c-di-GMP) positively regulates biofilm formation and negatively regulates virulence and is proposed to play an important role in the transition from persistence in the environment to survival in the host. (
  • A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase. (
  • Increased MrkH production subsequently drives mrkABCDF expression when activated by c-di-GMP, leading to biosynthesis of type 3 fimbriae and biofilm formation. (
  • Cyclic di-GMP is synthesized by biofilm formation, motility and induction of virulence factors. (
  • The bacterial second messengers (p)ppGpp and bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulate important functions, such as transcription, virulence, biofilm formation, and quorum sensing. (
  • Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990). (
  • This molecule, referred to as 2′3′-cGAMP (cyclic [G(2',5')pA(3',5')p]), functions as an endogenous second messenger inducing STING-dependent type I interferon response. (
  • A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity - a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. (
  • Riboswitches called the cyclic di-GMP-I riboswitch and cyclic di-GMP-II riboswitch regulate gene expression in response to cyclic di-GMP concentrations in a variety of bacteria, but not all bacteria that are known to use cyclic di-GMP. (
  • Furthermore, we identify mutations in STING that selectively affect the response to cyclic dinucleotides without affecting the response to DNA. (
  • These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP. (
  • Enzymes that degrade or synthesize cyclic di-GMP are believed to be localized to specific regions of the cell, where they influence receivers in a restricted space. (
  • Some diguanylate cyclase enzymes are allosterically inhibited by cyclic di-GMP. (
  • Taken together, these results showcase the application of RBF biosensors in visualizing single-cell dynamic changes in cyclic di-GMP signaling in direct response to environmental cues such as zinc and highlight our ability to assess whether observed phenotypes are related to specific signaling enzymes and pathways. (
  • Bacteria contain diverse c-di-GMP binding receptors/effectors, which exert the regulatory functions of this signaling molecule. (
  • McDonald L G, Murad F. Nitric oxide and cyclic GMP signaling. (
  • Nitric oxide and cyclic GMP formation induced by interleukin 1β in islets of Langerhans. (
  • 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. (
  • There have been and will continue to be many opportunities from nitric oxide and cyclic GMP march to develop novel and important therapeutic agents. (
  • In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. (
  • 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. (
  • 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. (
  • 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 ). (
  • However, a mammalian sensor of cyclic dinucleotides has not been identified. (
  • Here we report evidence that STING itself is an innate immune sensor of cyclic dinucleotides. (
  • Thus, STING seems to function as a direct sensor of cyclic dinucleotides, in addition to its established role as a signalling adaptor in the IFN response to cytosolic DNA. (
  • 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. (
  • Cyclic dinucleotides are an expanding class of signaling molecules that control many aspects of bacterial physiology. (
  • Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING. (
  • 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. (
  • 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. (
  • We also observed that with an influx of Zn 2+ in the environment, the transcription of the znuAeagA/znuBC gene cluster is regulated by both Zur and a yet to be characterized c-di-GMP dependent pathway. (
  • We propose that the deregulation of the PI3K/PDE3B pathway might result in increased intracellular cyclic AMP accumulation, which promotes apoptosis. (
  • The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence. (
  • Cyclic di-GMP levels regulate other processes via a number of mechanisms. (
  • 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. (
  • Alterations in the intracellular levels of cyclic-di-GMP (c-di-GMP) regulate the transition between the different stages of infection in E. amylovora . (
  • Thus, spatial separation of individual c-di-GMP signaling units was postulated. (
  • The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous small signaling molecule which greatly affects bacterial growth and behavior. (
  • Cyclic GMP signaling is important in many physiological responses including relaxation of smooth muscles, penile erection, kidney function and inflammatory responses1, 2, 3. (
  • 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. (
  • Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification. (
  • 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. (
  • 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. (
  • Global versus local c-di-GMP signaling modules. (
  • Two possible architectures of c-di-GMP signaling modules are schematically depicted. (
  • An, Shi Qi , Tang, Ji Liang and Dow, J. Maxwell (2017) Probing the role of cyclic di-GMP signaling systems in disease using Chinese radish. (
  • Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. (
  • 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. (
  • Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. (
  • Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. (
  • We show that the reporter constructs give a fluorescent readout of the intracellular level of cyclic di-GMP in P. aeruginosa strains with different levels of cyclic di-GMP. (
  • Specifically, we demonstrate that intracellular levels of cyclic di-GMP in Escherichia coli are repressed with excess zinc, but not with other divalent metals. (
  • 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. (
  • Left) Several DGCs and PDEs can contribute to a common global pool of c-di-GMP (black dots). (
  • This was shown using SKF94836 (PDE3 inhibitor) which maximally inhibited membrane-bound cyclic AMP PDE activity by approximately 25-30% and by RT-PCR. (
  • Schultz KD, Schultz K, Schultz G (1977) Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens. (
  • Two novel rat guanylin molecules, guanylin-94 and guanylin-16, do not increase cyclic GMP production in T84 cells. (
  • VieA controls the intracellular concentration of the cyclic nucleotide second messenger cyclic diguanylate (c-di-GMP) using an EAL domain that functions as a c-di-GMP phosphodiesterase. (
  • In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP . (
  • The potential glycosyl hydrolase YdaJ is not essential for the generation of the above-described phenotypes, whereas the presence of YdaK is required, implying an involvement of the second messenger c-di-GMP. (
  • In Pseudomonas fluorescens , this process is regulated by the Lap system and the second messenger cyclic-di-GMP. (
  • The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. (
  • We next isolated suppressor mutations in six phosphodiesterase genes, which reinstate motility in the absence of PdeH by reducing cellular levels of c-di-GMP. (
  • In agreement with this, we showed that overall cellular levels of c-di-GMP control pdeL transcription and that this control depends on PdeL itself. (
  • Recently, cell cycle control and regulated proteolysis have been added to this growing list of cellular functions controlled by c-di-GMP. (
  • Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions. (
  • Furthermore, in both flow cytometry and fluorescence microscopy setups, we monitor the dynamic increase in cellular cyclic di-GMP levels upon zinc depletion and show that this response is due to de-repression of the endogenous diguanylate cyclase DgcZ. (
  • STING is a direct innate immune sensor of cyclic di-GMP. (
  • 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. (
  • The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. (
  • Cyclic di-GMP influences diverse functions through interaction with a range of effectors. (
  • In Vivo Biochemistry: Single-Cell Dynamics of Cyclic Di-GMP in Escherichia coli in Response to Zinc Overload. (
  • Our results suggest a mechanism whereby c-di-GMP and c-di-AMP are detected by DDX41, which forms a complex with STING to signal to TBK1-IRF3 and activate the interferon response. (
  • Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP. (
  • Herein we describe a characterization of the infection-induced gene cdpA , which encodes both GGDEF and EAL domains, which are known to mediate diguanylate cyclase and c-di-GMP phosphodiesterase (PDE) activities, respectively. (
  • The BLItz system was used to study binding between STING CBD (c-di-GMP binding domain) and IKK-like kinase TBK1. (