Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre-or post-synaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intrcellular injection techniques should minimize this particular problem, although possibly at the expense of new diffulties. Prio blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Utimately, the developement of highly specific inhibitor for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the action of cyclic GMP and the role of its synthesizing enzyme, guanylate cyclase. The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.
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PMID:The role of cyclic nucleotides in the CNS. 1 46

We estimated nucleotide pyrophosphatase and phosphodiesterase I activities in human and rat organs and in body fluids from man and dog. The highest organ activities were found in epididymis, kidney, liver, and intestine. In body fluids, the activity was highest in seminal plasma, followed by intestinal lymph, serum, heart lymph, cerebrospinal fluid, milk, and urine. The ratio nucleotide pyrophosphatase/phosphodiesterase I and the urea resistance of phosphodiesterase I differed among human organs, body fluids, and blood cells. Different isoenzymes probably exist. The activities in serum share several properties with those in several organs--e.g. pH-optimum 9.6-9.8, dependency on Zn2+, and the effects of inhibitors. Phosphodiesterase I in erythrocytes, which has not been described previously, differs from enzyme from other sources by lower pH optimum (8.5), dependency on Mg2+, inhibition by Zn2+, and stimulation by dithiothreitol.
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PMID:Nucleotide pyrophosphatase and phosphodiesterase. I. Organ distribution and activities in body fluids. 1 63

The effects of adrenergic and cholinergic agents as well as the effects of disodium cromoglycate (DSCG) on the levels of cyclic AMP and cyclic GMP in mouse lung fragments were studied. Levels of cyclic AMP were enhanced by two of the known beta-adrenergic agonists, epinephrine and isoproterenol. This increase was abolished by propanolol, a recognized beta-adrenergic antagonist. Disodium cromoglycate, a proposed inhibitor of phosphodiesterases, alone caused a slight, significant increase in cyclic AMP. However, in the presence of epinephrine, levels of cyclic AMP were potentiated by DSCG. DSCG behaves, therefore, as a typical cyclic AMP phosphodiesterase inhibitor. Cyclic GMP levels were increased by carbachol, acetylcholine, and the phosphodiesterase inhibitor, aminophylline, but not by DSCG, or beta-adrenergic agonists.
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PMID:Regulation of intracellular cyclic GMP and cyclic AMP levels in mouse lung fragments by disodium cromoglycate, beta-adrenergic agonists, cholinergic activators, and histamine. 1 25

The levels of cyclic adenosine monophosphate (cAMP) and two forms of cAMP phosphodiesterase with low (PDE1) and high (PDE2) affinity for the substrate were determined in homogenates from mouse liver and transplanted hepatoma 22. The level of cAMP in the tumour is 3 times lower than that in liver. By te kinetic parameters (Vmax, Km, pH optimum) adenylate cyclase from tumour does not show any significant differences as compared to the liver enzyme; the enzyme from hepatoma is, however, more sensitive to activation by F- ions. The activities of adenylate cyclase in liver and tumour cells are the same. Phosphodiesterases of cAMP from tumour and liver cells are similar in their Km values (3,3-10(-4) M for PDE1 and 2-10(-6) M for PDE2); however, the maximal and real rates of cAMP hydrolysis in hepatoma are much higher than in liver. The fact that both cAMP phosphodiesterase activities have similar dependence on Mg2+ and Ca2+ concentrations, suggests that PDE1 is a latent form of PDE2. In tumour cells the equilibrium between these two forms is probably shifted towards the enzyme with high affinity for the substrate. The results suggest that a decreased cAMP level in hepatoma cells (as compared to the liver) is due to the activation of PDE2.
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PMID:[Some features of cyclic adenosine monophosphate metabolism in mouse liver and hepatoma 22]. 2 Jan 68

1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
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PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

Human urine RNase was purified about 2000-fold. The preparation is free from phosphatase, phosphodiesterase and DNase activities. On electrophoresis through polyacrylamide gel at pH 8.3, it migrates toward the anode and stains with periodic acid-Schiff reagent, suggesting that it is acidic and glycoprotein in nature. Its isoelectric point is at pH 4.1. It has a molecular weight of about 21,500. It is thermostable at pH 4.2 and thermolabile at pH 8.5. It has a pH optimum at 6.5. It exhibits highest preference for cytidine 3'-phosphate linkages. Its activity on poly (C) is endonucleolytic. It cleaves poly (C) via intramolecular transphosphorylation. It has no action on cytidine 2': 3'-cyclic phosphate or uridine 2':3'-cyclic phosphate. Its rate of hydrolysis of poly (U) is less than 2% of that of poly C). Poly (A) and poly (G) are totally inert to its action. Its action on poly (C) is inhibited by poly (G), poly (A) and poly (U). It differs from bovine pancreatic Rnase A in its physical, chemical and catalytic properties. It is, however, similar to human serum and pancreatic RNase in all its properties, suggesting that pancreas is its likely source.
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PMID:Purification and properties of a ribonuclease in human urine that hydrolyses polycytidylic acid. 2 Jun 15

The norepinephrine-sensitive adenylate cyclase system in the rat brain was examined. Adrenergic blocking agents and the relative activity of structurally related catecholamines were employed to determine whether norepinephrine-stimulated accumulation of [3H]c-AMP in the hypothalamus occurred via alpha or beta adrenergic receptors. The results indicate that norepinephrine probably acts through a mixture of alpha and beta receptors in that both alpha and beta adrenergic blockers inhibited norepinephrine-induced accumulation of [3H]c-AMP. Morphine and levorphanol had no significant effect on adenylate cyclase or phosphodiesterase activities in hypothalamic slices or homogenates of several brain regions.
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PMID:Norepinephrine-sensitive adenylate cyclase in rat hypothalamus: effects of adrenergic blockers and narcotics. 2 29

The cardiolipin phosphodiesterase of Escherichia coli was further characterized. This enzyme has a pH optimum of 7.0 and is Mg2+ dependent. Mn2+ and Co2+ could replace Mg2+ but other divalent cations were inhibitory or without effect. The enzyme is not periplasmic and does not appear to be associated with membrane fractions prepared by different methods. It is recovered as a soluble protein in the cytosol fraction but could not be readily purified because of its instability. With cell-free systems, a requirement for ATP or ADP could be shown under certain defined conditions. Other nucleotides were less effective or ineffective in stimulating the phosphodiesterase. The cells displayed the highest activity during the middle to late exponential stage but no marked requirement for ATP was apparent when the phosphodiesterase was obtained from such freshly grown cells. If, however, cells were starved for several hours in saline medium, the cardiolipin phosphodiesterase level fell and a requirement for added ATP could be shown. The cardiolipin phosphodiesterase is an enzyme distinct from cardiolipin synthase. The assay conditions are quite different from each of these enzymes as are their subcellular distributions.
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PMID:Further studies on the cardiolipin phosphodiesterase of Escherichia coli. 2 9

The DNAase in human urine was purified about 30-fold with a recovery of 28%. This involved DEAE-cellulose and phosphocellulose chromatography steps and gel filtration on Sephadex G-75. The enzyme required divalent cations such as Co2+, Mg2+, Mn2+ and Zn2+ for activity, but Ca2+, Cu2+ and Fe2+ were ineffective. EDTA and G-actin inhibited the reaction. The maximum activity was observed at pH 5.5 in acetate buffer plus Co2+ or Mg2+ and Ca2+. It had a molecular weight of approximately 38 000, estimated by gel filtration on Sephadex G-75 and isoelectric point of around pH 3.9. The enzyme is an endonuclease which hydrolyzes native, double-stranded DNA about 3 to 4 times faster than thermally denatured DNA to produce 5'-phosphoryl- and 3'-hydroxyl-terminated oligonucleotides. The final preparation was free of non-specific acid and alkaline phosphatases, phosphodiesterase and ribonuclease activities.
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PMID:Purification and properties of deoxyribonuclease from human urine. 2 31

Vicia faba root cells contain several nucleolytic activities: phosphomonoesterase and phosphodiesterase (which however were not studied in details), one nuclease and four ribonucleases. These results were obtained by separating the extracted proteins into anionic and cationic species by chromatography on CM-cellulose at pH 5.5 and analysing each kind of proteins. Anionic species were subjected to chromatography on DEAE-cellulose which lead to isolation of one nuclease (A1) and two RNAases (A2, A3), the properties of which were studied. It was shown that the RNAases pH optima are near 6; A2 is more thermolabile than A3; both are endonucleases unable to attack double-stranded structure; studies with homopolymers, i.e. poly(A), poly(I), poly(C), poly(U), showed that their base specificities were analogous to that of already known plant RNAases. The cationic proteins, analysed with CM-cellulose, contain two RNAases (C1, C2). The pH optima were near 6 and 7, respectively; C1 is much more thermolabile than C2; both were endonucleases inactive on double-stranded structures. C1 and C2 hydrolysed poly(C) and poly(U) but not poly(A) and poly(U).
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PMID:Study on plant RNAases. Isolation and properties of several activities from Vicia faba root cells. 2 32


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