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)

Effects of 20,25-diazacholesterol (DAC), a myotonia-inducing drug, were evaluated on certain biochemical and morphological properties of embryonic rat muscle cells grown in tissue culture. During DAC treatment, muscle fibers exhibited spontaneous contractions that changed from coarse twitches to finer fibrillation movements, The ultrastructural alterations produced by DAC were smeared Z-lines, disorganized myofibrils, occasional honeycomb appearance of membranes and large vacuoles connected to zipper-like structures. Biochemically, a microsomal fraction prepared from DAC-treated cells (compared to that of normal cells) showed a 30-45 per cent decrease in the isoproterenol-enhanced and the NaF-enhanced adenylate cyclase activity. however, the beta-adrenergic receptors, through which isoproterenol activates the enzyme, showed no change in density or affinity as judged by the binding of [125I]iodohydroxybenzylpindolol. That indicated that DAC treatment caused an uncoupling of beta-receptor-adenylate cyclase interaction. Guanylate cyclase and cyclic GMP-phosphodiesterase were both markedly increased in DAC-treated cells, indicating a greater turnover of cyclic GMP. Binding of [3H]concanavalin A to DAC-treated muscle membranes was decreased 20-40 per cent. The data indicate that DAC exert a direct influence on muscle fibers, affecting their functional, biochemical and morphological properties.
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PMID:Biochemical and morphological effects of 20,25-diazacholesterol on cultured muscle cells. 705 57

Plasma membranes were isolated from lactating bovine mammary gland. Two crude membrane fractions; medium/d 1.033 (light membrane) and 1.033/1.053 interfaces (heavy membrane), were obtained by Ficoll density gradient centrifugation of osmotically washed microsomal fraction. Two crude membranes were further purified separately by sucrose density gradient centrifugation. Both light and heavy membranes banded at a sucrose density of 1.14. The purified membranes appeared as heterogeneous smooth membrane vesicles on electron microscopy. The contaminating suborganelles were not detected. The yield of the purified membranes relative to the homogenate was 1.2%. The degree of purity of the membranes was shown by a great increase in the specific activity of 5'-nucleotidase over the homogenate of 20-fold for light membrane and of 16-fold for heavy membrane. The relative activities of Mg2+-ATPase, (Na+ + K+)-ATPase, gamma-glutamyl transpeptidase, phosphodiesterase I, alkaline phosphatase and xanthine oxidase were also high (12-18-times) and nearly 20% of these enzymes was recovered. The activity of marker enzyme for mitochondria, endoplasmic reticulum and Golgi apparatus was very low, while that of acid phosphatase for lysosome was relatively high (5-times). DNA and RNA contents were very low. The major polypeptides rich in other suborganelles were not detected profoundly in the membrane fraction and the polypeptide composition in both light and heavy membranes were similar upon SDS-polyacrylamide gel electorphoresis.
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PMID:Isolation and characterization of plasma membrane from lactating bovine mammary gland. 720 55

The effects of papaverine, cyclic AMP and MIX(3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor) on calcium uptake by a microsomal fraction from rat uterus were tested in the presence of 3 mM ATP. Papaverine potentiated calcium uptake in the presence of oxalate but inhibited it in the absence of oxalate. However, cyclic AMP and MIX did not influence calcium uptake, neither in the presence nor the absence of oxalate. These results suggest that calcium uptake by plasma membrane-derived vesicles in the absence of oxalate is inhibited by papaverine and that papaverine potentiated calcium uptake by the internal membranes in the presence of oxalate. They suggest also that the stimulatory action of papaverine involves a cyclic AMP-independent mechanism in addition to the mechanism via cyclic AMP.
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PMID:A dual action of papaverine on calcium uptake by microsomal fraction isolated from rat uterus. 721 34

A procedure for cellular fractionation and preparation of plasma membrane from a Burkitt's lymphoma cell line is described. This procedure involves homogenization with a Polytron in buffered isotonic sucrose, and separation of cellular fractions by differential and isopycnic centrifugation in sucrose. The isolated plasma membrane fraction contains 44% of the cellular cholesterol, 50% of the ouabain-sensitive (Na+ + K+)-ATPase activity, 43% of the gamma-glutamyltranspeptidase activities and 16% of the phospholipid. This fraction contains only 3% of cellular protein and is contaminated with less than 4% of the total cellular activities of microsomal, lysosomal, mitochondrial, Golgi and soluble marker enzymes. The cholesterol : phospholipid molar ratio of the crude plasma membrane is 0.56. The membranes in this fraction are in the form of vesicles. Further purification of plasma membrane is achieved by sucrose density gradient centrifugation and results in a 25- to 30-fold enrichment of plasma membrane markers. Plasma membrane markers band in these gradients between 1.10 and 1.15 g/cm3. The distribution patterns in the cell fractions of 18 cellular constituents are quantitatively determined. Most constituents are found to distribute in a fashion consistent with the results obtained in other systems. Thymidine-5'-phosphodiesterase (phosphodiesterase I), esterase, nucleoside diphophatase and glucose-6-phosphatase, however, are shown to be poor markers of membrane fractions in this system. Lactoperoxidase-catalyzed iodination was used to identify several plasma membrane proteins which are exposed at the surface. After separation of labeled polypeptides by sodium dodecyl sulfate gel electrophoresis, the predominant labeled protein was identified as the heavy chain of IgM. Several lesser labeled proteins were observed.
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PMID:Cellular fractionation and isolation of the plasma membrane of Burkitt's lymphoma cells. 740 42

Metabolic effects of dexamethasone (DX) on the noninfarcted functioning myocardium were studied in rabbits with experimental coronary artery ligation to evaluate the usefulness of glucocorticoids in acute myocardial infarction. Maximum active tension of noninfarcted area of the isolated perfused hearts was markedly reduced 6 hr, 2 days, and 5 days after ligation, associated with significant decreases in norepinephrine (NE) and cAMP contents, but with no changes in adenylate cyclase (AC) and cAMP phosphodiesterase (PDE) activities. Calcium content of mitochondrial fraction was considerably increased in the peri- and noninfarcted area without any changes in microsomal CA2+ or myocardial total Ca2+. Ca2+ uptake rate and Ca2+-dependent ATPase activity of the sarcoplasmic reticulum fraction from the operated hearts were markedly reduced. Intramuscular administration of DX (3 mg/kg body wt/day) for 2 days after operation significantly improved these reductions in myocardial function and metabolism. In normal hearts from animals without infarction, DX caused 48% elevation in basal cAMP level, marked reductions in mitochondria and microsomal Ca2+, and 26% decrease in PDE activity, although no changes in myocardial total Ca2+ AC activity and myocardial contractility were observed. NE-induced inotropic effects were markedly enhanced in both control and operated groups with DX treatment. These results indicated that large doses of DX would improve the reduced myocardial function and metabolism in acute myocardial infarction by increasing basal cAMP level and by its influence on intracellular Ca2+ available for cellular activity.
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PMID:The effects of large doses of dexamethasone on myocardial contractility and calcium metabolism in experimental myocardial infarction. 742 58

Bradykinin causes a concentration-dependent, transient rise in intracellular Ca2+ and a sustained inhibition of forskolin-, dopamine- and 5'-N-ethyl-carboxamidoadenosine (NECA)-stimulated cAMP accumulation in D384 astrocytoma cells. Chelation of intracellular calcium abolished bradykinin's inhibitory effect on cAMP accumulation. Chelating extracellular Ca2+ did not block the initial, but eliminated the sustained inhibition of cAMP accumulation. Increasing Ca2+ influx by calcium ionophore A23187 caused a concentration-dependent inhibition of stimulated cAMP accumulation. A hydroquinone derivative 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), which inhibits microsomal Ca2+ sequestration, did not mimic the effect of bradykinin, although it increased [Ca2+]i even more than A23187 did. The inhibitory effect of bradykinin was not mediated by Ca2+/CaM-dependent stimulation of phosphodiesterase (PDE). Forskolin-stimulated adenylyl cyclase activity was inhibited by Ca2+ (10(-7) to 10(-3) M), both in ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) washed and native D384 plasma membranes. This effect was not altered by calmodulin (CaM) or CaM-antagonists. Bradykinin treatment, which attenuates cAMP accumulation in intact cells, did not do so in plasma membranes. These findings suggest that bradykinin-induced inhibition of cAMP formation in D384 cells requires mobilization of [Ca2+]i and subsequent entry of Ca2+ which directly interacts with a component of the adenylyl cyclase system.
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PMID:Bradykinin inhibits cyclic AMP accumulation in D384-human astrocytoma cells via a calcium-dependent inhibition of adenylyl cyclase. 768 45

Rat retina tissue contains relatively high amounts of GD3 in relation to ganglio-series gangliosides even in the adult stages. This was attributed in part to an activity ratio between the enzyme that converts GM3 to GD3 [sialytransferase II (ST-II)] and the enzyme that converts GM3 to GM2 [N-acetylgalactosaminyltransferase (GalNAc-T)] favorable to ST-II. Here we report the presence in the rat retina tissue of an activity that hydrolyzes one of the substrates of GalNAc-T, the donor sugar nucleotide UDP-GalNAc. Chromatographic analyses of the products of degradation indicate that the activity corresponds to a UDP-sugar pyrophosphatase/phosphodiesterase I. The activity is developmentally regulated, increasing after day 4 of postnatal development to reach values approximately 10-fold higher in the adult tissue. The activity sediments with the microsomal membranes, also hydrolyzes UDP-Gal, does not hydrolyze CMP-NeuNAc, requires Mn2+, and does not require detergent. Kinetic data showed that the same activity hydrolyzes UDP-GalNAc and UDP-Gal, each one acting as competitive inhibitor for the hydrolysis of the other (Km and Ki for UDP-GalNAc, 48 and 33 microM, respectively; Km and Ki for UDP-Gal, 5 and 12 microM, respectively). In another set of experiments, it was found that the activities of the GalNAc-T and the enzyme that converts GM2 to GM1 [galactosyltransferase II (Gal T-II)] increased about threefold from birth to day 4 and then decreased to stabilize by day 6 in values that were similar to those at birth and about one-half those of ST-II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A UDP-sugar pyrophosphatase is developmentally regulated in the rat retina. 786 Nov 60

According to their respective elution order, specificity for cAMP and cGMP, their sensitivity to calmodulin, and their modulation by cGMP and rolipram, four cyclic nucleotide phosphodiesterases (PDE) were separated from the cytosol: PDE I (calmodulin-sensitive), PDE II (stimulated by cGMP, PDE IV (cGMP specific-PDE and inhibited by rolipram) and PDE V (cGMP specific). PDE IV (Km = 1.4 microM) was competitively inhibited by rolipram (Ki = 1.2 microM) whereas PDE V (Km = 0.83 microM) was competitively inhibited by zaprinast in the mumolar range (Ki = 0.12 microM). Moreover the microsomal fraction contained three PDE isoforms: PDE II, PDE III (inhibited by cGMP or indolidan) and PDE IV. These results show that cAMP degradation in cytosolic and membrane fractions is modulated by cGMP and selectively inhibited by rolipram and, in addition, by indolidan in membrane fractions.
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PMID:Biochemical and pharmacological characterization of cyclic nucleotide phosphodiesterase in airway epithelium. 789 88

The distribution of phosphodiesterase (PDE) activities was studied in canine cardiac microsomal fractions separated by sucrose density gradient (fractions F1 to Fv1). These fractions were characterized by their 45Ca2+ uptake and release properties, [3H] ryanodine binding [used as sarcoplasmic reticulum (SR) markers] and their [3H]nitrendipine binding (as a T-system marker). The solubilized canine and human SR-enriched membranes were subjected to high performance liquid chromatography and the PDE forms were then analyzed for their kinetic properties and drug sensitivies. In human SR, a notable amount of PDE I hydrolyzing both cAMP and cGMP was characterized; however, its stimulation by calmodulin was reduced. Two selective cAMP-PDE forms were identified in the canine and human cardiac SR-enriched fractions. The major form presents the characteristics of PDE III: an apparent Km value of 0.29 and 0.35 microM in canine and human cardiac SR, respectively, potent inhibition by cGMP and AAL 05 > cilostamide > Cl 930 > indolidan, and insensitivity to rolipram. The other form displays the properties of PDE IV: an apparent Km value of 1.4 and 1.3 microM in canine and human cardiac SR respectively, potent inhibition by rolipram and poorly sensitive to inhibition by PDE III inhibitors. The PDE IV distribution in canine SR suggests that this form is mostly associated with the FII fraction enriched in sarcolemmal membranes. In contrast, PDE III assessed by its indolidan sensitivity and [3H]LY186126 binding is associated with the microsomal membranes enriched in vesicles derived from T-tubule and junctional SR membranes. Because these membranes are directly involved in controlling excitation-contraction coupling, such PDE location enhances the physiologic relevance to study their implication in regulating cardiac contraction.
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PMID:Characterization of indolidan- and rolipram-sensitive cyclic nucleotide phosphodiesterases in canine and human cardiac microsomal fractions. 838 53

While steady-state kinetic parameters (metabolite pools, Km and activation energies) are partially known for the enzymes involved in phosphatidylcholine synthesis and degradation in mammalian brain, they are not available for the nervous system of lower vertebrates or invertebrates. Since the extent of evolutionary development of an enzyme is not known a priori, we evaluated the kinetic and thermodynamic parameters of choline kinase, CTP:phosphocholine cytidylyltransferase, choline phosphotransferase and glycerophosphorylcholine phosphodiesterase in squid (Loligo pealei) optic lobe, dogfish (Mustelus canis) and rat brain. For all these enzyme activities, basic similarities in Km and inhibitor effect were found. The same was true for the activation energies Ea, with the exception of squid choline kinase and dogfish cytidylyltransferase. Treatment of microsomal membranes with phospholipase C sharply inhibited cytidylyltransferase activity in all three animal species. In dogfish brain, glycerophosphorylcholine phosphodiesterase activity was undetectable. Our results are consistent with the notion that the kinetic properties of the enzyme activities leading to the preservation of the phosphatidylcholine membranous pool may have appeared early in metazoan evolution and been fully conserved in mammals.
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PMID:Evolutionary comparison of enzyme activities of phosphatidylcholine metabolism in the nervous system of an invertebrate (Loligo pealei), lower vertebrate (Mustelus canis) and the rat. 852 26


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