Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Fragments of sarcoplasmic reticulum from rabbit sceletal muscles sedimented within the range from 2000 g to 8000 g (heavy fraction) and 8000 g to 40000 g (light fraction) and washed with 0.6 M KCl, were practically free of adenylatecyclase activity. Phosphodiesterase cAMP was not found in the light fraction, while its activity in the heavy fraction was 500 pmol of cAMP/min per mg of protein. Both fractions contain bound cAMP (1-2 pmol/mg of protein) and specific sites of cAMP binding, the binding constant being approximately 10(6)M-1. The number of binding sites is 60 pmol/mg of protein for the heavy and 30 pmol/mg of protein for the light fractions. The level of phosphodiesterase activity in the heavy fraction correlates with its sensitivity to imidazole, anserine and caffeine. Imidazole and anserine increase in 1.5-1.8 times the value of Ca2+/ATP in the heavy fraction and produce no effect on Ca2+ transport by the light fraction. Caffeine decreases almost twice the Ca2+/ATP value in the heavy fraction and has practically no effect on Ca2+ absorption by enzymes of the light reticulum fraction. Imidazole and anserine activate membrane-bound phosphodiesterase, while caffeine inhibits it. It is suggested that structural rearrangements of membrane-bound phosphodiesterase under the effect of caffeine, imidazole and anserine are responsible for changes in the efficiency of Ca2+ transport by fragments of the heavy reticulum fractions.
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PMID:[Concentration of components of the adenylate system in heavy and light fractions of the sarcoplasmic reticulum of skeletal muscles and sensitivity of these fractions to the effects of imidazole-containing compounds and caffeine]. 18 55

A method for isolating a plasma membrane-enriched fraction and other subcellular fractions from rat mesenteric arteries by the use of a discontinuous sucrose density gradient is decribed. Electron microscopy showed both plasma membrane and endoplasmic reticulum fractions to be composed of vesicles. 5'-Nucleotidase, alkaline phosphatase, ouabain-sensitive (Na+ + K+)-ATPase and K+-phosphatase, and phosphodiesterase I were concentrated in the plasma membrane fraction. The increase in ATP-dependent calcium uptake in the presence of oxalate was greater in the endoplasmic reticulum than in the plasma membrane fraction. The lack of inhibition of active calcium uptake by azide suggests that the plasma membrane-enriched fraction was relatively free of mitochondrial contamination. Calcium uptake by the plasma membrane or the endoplasmic reticulum fraction was not enhanced by high-energy compounds other than ATP, and was little affected by 100 mM KCl or NaCl in the Mg++-containing medium. Subcellular fractions isolated by this method will be useful for investigating the biochemistry of small blood vessels of the rat.
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PMID:Isolation and characterization of plasma membrane from rat mesenteric arteries. 18 63

2-Fluoroadenosine (F-Ado) is a potent inhibitor of lymphocyte-mediated cytolysis studied in vitro. The inhibition of cytolysis by F-Ado was potentiated markedly by an inhibiotr (Ro 20-1724) of adenosine 3':5'-monophosphate (cAMP) phosphodiesterase and, unlike the inhibition caused by adenosine, was irreversible when the cytotoxic lymphocytes were incubated with F-Ado and were then washed free of exogenous nucleoside. Incubation of cytotoxic lymphocytes with F-Ado resulted in the rapid, dose-dependent formation of 2-fluoroadenosine 5'-triphosphate (F-ATP); the build-up of F-ATP within these cells was accompanied by a reciprocal depletion of ATP. Once formed intracellularly, the F-ATP was not diminished during a subsequent 30-min incubation of the cells in F-Ado-free medium. 2-Fluoroadenosine 3':5'-monophosphate (F-cAMP), a novel compound, was synthesized chemically. This cAMP analogue was found to be highly cross-reactive in a radioimmunoassay specific for cAMP and to be equipotent to cAMP in its ability to activate a crude preparation of protein kinase derived from rat brain. A column chromatographic procedure was devised whereby F-cAMP and cAMP could be purified simultaneously from tissue extracts. Treatment of cytotoxic lymphocytes with F-Ado resulted in the formation of presumptive F-cAMP in amounts greater than that of cAMP, as determined by the concentration of F-Ado added to the medium and was not observed when the lymphocytes were incubated with either adenosine or 2-chloroadenosine, two agents which caused large increases in cAMP. The simultaneous presence of Ro 20-1724 enhances greatly the formation of F-cAMP from F-Ado without affecting the pool size of F-ATP. Removal of exogenous F-Ado from cells previously incubated with this drug and subsequent incubation of these cells in drug-free medium did not result in a substantial reduction in intracellular F-Ado (via prior incubation with F-Ado); 2'-deoxyadenosine was also effective in this capacity, while 9-beta-D-arabinofulanosyladenine was without effect. The level of cAMP was elevated transiently, in a dose-dependent manner, by F-Ado, and returned to control value after removal of exogenous F-Ado from the cells. Ro 20-1724 enhanced greatly this transient elevation of cAMP caused by F-Ado.
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PMID:2-Fluoroadenosine 3':5'-monophosphate. A metabolite of 2-fluoroadenosine in mouse cytotoxic lymphocytes. 18 17

Adenosine, AMP, ADP and ATP activated adenylate cyclase in pig skin (epidermis) slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, papaverine. But another inhibitor, theophylline, strongly blocked the activation of adenylate cyclase by adenosine and adenine nucleotides. Theophylline apparently competed with adenosine for the cell surface receptor. Like theophylline, the addition of adenine alone caused no accumulation of cyclic AMP, but it significantly inhibited the stimulatory effect of adenosine. Guanosine, or guanine, cytidine, uridine, or thymidine nucleotides had no effect on the accumulation of cyclic AMP. Among other adenine nucleotides we tested, adenosine 5'-monophosphoramidate, but not adenosine 5'-monosulfate significantly increased cyclic AMP especially with the addition of papaverine. Neither 2'- nor 3'-adenylic acid were effective. Our data indicate that pig epidermis has four specific and independent adenylate cyclase systems for adenosine (and adenine nucleotides), histamine, epinephrine and prostaglandin E.
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PMID:Adenosine and adenine nucleotides stimulation of skin (epidermal) adenylate cyclase. 18 2

Membranes of rat caudate nucleus contain a dopamine-dependent adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and a Ca++ binding protein that activates phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17). This activator can be released from the membranes by a phosphorylation with a 3':5' cAMP-dependent protein kinase (ATP-protein phosphotransferase, EC 2.7.1.37). Under the conditions of membrane phosphorylation and activator release, dopamine fails to activate striatal adenylate cyclase. The basal activity of this enzyme is not decreased by the release of the protein activator but the activation by NaF is reduced. Adenylate cyclase is not phosphorylated when the dopamine activation is blocked after the release of the activator, but other membrane proteins are phosphorylated. It is postulated that the endogenous protein stored in striatal membranes can regulate the intracellular concentration of cAMP by an activation of adenylate cyclase while stored in striatal membrane, and by an activation of phosphodiesterase when released into the cytosol after membrane phosphorylation.
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PMID:Regulation of dopamine stimulation of striatal adenylate cyclase by an endogenous Ca++ -binding protein. 18 77

The interaction of various spin-labeled compounds with the murine thymocyte adenylate cyclase-cyclic AMP system was investigated. Electron paramagnetic resonance spectra from spin-labeled compounds were used to calculate the order parameter, S, and indicated that the thymocyte plasma membrane is a relatively rigid structure. Increasing concentrations of spin-labeled stearates, but not their corresponding methyl esters, resulted in increased membrane fluidity, partial lysis, and concomitant complete inhibition of cholera toxin-mediated increases in cyclic AMP content. Upon subsequent isolation of plasma membranes from these cells, cholera toxin-stimulated adenylate cyclase activity was also completely inhibited. Direct addition of spin-labeled stearates, but not spin-labeled methyl stearates, to thymocyte homogenates caused a dramatic reduction of basal, cholera toxin-, isoproterenol-, NaF-, and prostaglandin E1-stimulated adenylate cyclase activity. Inhibition was complete within the first minute of addition to homogenates and required approximately 0.2 mM spin-labeled stearate I(12,3) for half-maximal inhibition. This inhibition occurred in the presence or absence of an ATP-regenerating system and was not readily reversible. Furthermore, since the membrane cyclic phosphodiesterase activity was not altered by spin-labeled stearates, their inhibition was attributed to a direct action of stearate spin labels on adenylate cyclase. Neither stearate, methyl stearate, spin-labeled methyl stearates nor 2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempo) altered cell viability or enzyme activities at the concentrations studied. Spin-labeled stearates seemed to intercalate into different areas of the plasma membrane than their corresponding methyl esters. Furthermore, the action of spin-labeled stearates appeared to be on the exterior of the plasma membrane rather than the interior. These results illustrate the presence of multilipid domains and the importance of selected lipids and lipid-protein interactions in the adenylate cyclase-cyclic AMP system. Thymocyte adenylate cyclase is described in terms of a current model for membrane proteins.
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PMID:Spin-labeled stearates as probes for microenvironment of murine thymocyte adenylate cyclase-cyclic adenosine 3':5'-monophosphate system. 18 88

Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.
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PMID:Hyperreactive arterial endothelial cells: a clue for the treatment of atherosclerosis. 18 68

The effects of ethanol on adenylate cyclase and phosphodiesterase activity in vitro, and on cyclic AMP, ATP and adenosine levels in vivo were studied. Ethanol appeared to affect the cyclic AMP system indirectly, probably through its effect on neurotransmitter release or on adenosine formation.
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PMID:Effect of ethanol on the cyclic AMP system in rat brain. 18 35

The influence of various cyclic nucleotides on in vitro haemoglobin synthesis has been examined in suspension cultures of mammalian marrow cells. Over a wide range of concentrations, dibutyryl cyclic AMP (db-cAMP) was either ineffective or inhibited haemoglobin synthesis by marrow cells from rat, mouse and guinea-pig. However, 10(-3) M db-cAMP consistently stimulated haemoglobin synthesis in cultures of human, sheep, rabbit and canine cells, with the latter being most responsive. This effect, which approached in magnitude that of erythropoietin (ESF) itself, was specific for cAMP and its mono- and dibutyryl derivatives and was not inhibited by anti-ESF. Adenosine, AMP, ADP, ATP, cGMP, db-cGMP, cCMP, cIMP and sodium butyrate were either inactive or inhibitory at similar concentrations. Enhancement of haemoglobin synthesis was also observed with the phosphodiesterase inhibitor, RO-20-1724. The susceptibility to ionizing radiation of the response to ESF and db-cAMP was marked, indicating that the increased haemoglobin synthesis in this system was proliferation dependent, although the response to db-cAMP was less radiosensitive. Studies with tritiated thymidine showed that about 50% of the cells which were responding to either db-cAMP or ESF were actively engaged in DNA synthesis. However, the physical characteristics of db-cAMP-and ESF-responsive cells were dissimilar as analysed by their velocity sedimentation properties. These studies demonstrate that cAMP has a major stimulatory effect on haemoglobin synthesis with cells from selected mammalian species with activity approaching that of ESF, but the target cells most responsive to these agents appear different. The results suggest that cyclic nucleotide-related mechanisms may modulate in vitro erythropoiesis.
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PMID:Studies of the influence of cyclic nucleotides on in vitro haemoglobin synthesis. 19 63

Frog rod outer segments freshly detached from dark-adapted retinas contain approximately 1-2 molecules of guanosine 3',5'-cyclic monophosphate (cyclic GMP) for every 100 molecules of visual pigment present. This cyclic GMP decays to 5'-GMP, and the conversion is accelerated upon illumination of the outer segments. Bleaching one rhodopsin molecule can lead to the hydrolysis of 1,000-2,000 molecules of cyclic GMP within 100-300 ms. The decline in cyclic GMP concentration becomes larger as illumination increases, and varies with the logarithm of light intensity at levels which bleach between 5 X 10(2) and 5 X 10(5) rhodopsin molecules per outer segment-second. Light suppression of plasma membrane permeability, assayed in vitro as light suppression of outer segment swelling in a modified Ringer's solution, occurs over this same range of light intensity. The correlation between cyclic GMP and permeability or swelling is maintained in the presence of two pharmacological perturbations: papaverine, a phosphodiesterase inhibitor, increases both cyclic GMP levels and the dark permeability of the plasma membrane; and beta,gamma-methylene ATP increases the effectiveness of light in suppressing both permeability and cyclic GMP levels.
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PMID:Guanosine 3',5'-cyclic monophosphate and the in vitro physiology of frog photoreceptor membranes. 19 13


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