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)

Addition of IgG-sensitized human erythrocytes to peripheral blood monocytes elicit a transient increment in monocyte cAMP levels. This increase in cAMP was facilitated when monocytes were preincubated with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and theophylline, and the adenylate cyclase agonists, isoproterenol and prostaglandin E1 (PGE1). Although these cAMP elevating agents were able to inhibit monocyte ADCC, the degree of inhibition could not be anticipated from the cAMP levels achieved by these drugs since theophylline inhibited monocyte ADCC in doses not elevating cAMP and PGE1, isoproterenol and IBMX were less effective inhibitors of monocyte ADCC than theophylline when comparing their effects on cAMP levels. Both PGE1-induced elevation of cAMP levels and the further increments of cAMP after addition of IgG-sensitized erythrocytes to PGE1-treated monocytes were significantly correlated to the inhibition of beta-glucuronidase release during ADCC. Theophylline in doses of 0.5 mM did not elevate basal levels of monocyte cAMP but facilitated the ADCC-induced cAMP increment concomitant with inhibition of monocyte ADCC and degranulation. Possibly, facilitation of cAMP increments during ADCC by an inhibitory feedback mechanism may be responsible for the inhibition caused by cAMP-elevating agents.
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PMID:Facilitation of cAMP increments during ADCC mediated by monocytes pretreated with cAMP-elevating agents. 619 93

The biochemical properties of polymorphonuclear neutrophils from blood and peritoneal exudates of rabbits were compared. All enzymes measured showed almost identical activities in both types of cells, except for alkaline phosphodiesterase, the activity of which was seven times higher in peritoneal neutrophils. During phagocytosis, blood and peritoneal beta-glucuronidases were released in very similar fashions. Lysozyme, one of the enzymes concerned with killing of bacteria, as well as beta-glucuronidase, showed the same releasing pattern in both types of cells, but peroxidase was hardly released. Although superoxide anion generation in peritoneal neutrophils was two times higher than superoxide generation in blood neutrophils, phagocytic and bactericidal activities were almost the same in blood and peritoneal neutrophils. Blood neutrophils were more resistant to hypotonic lysis than were peritoneal neutrophils. These results show that there are no distinct differences in enzymatic and functional properties between blood and peritoneal polymorphonuclear neutrophils, except for alkaline phosphodiesterase activity, superoxide anion production, and osmotic fragility.
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PMID:Biochemical properties of polymorphonuclear neutrophils from venous blood and peritoneal exudates of rabbits. 626 Jun 50

Zymosan coated with complement (Zc) was observed to induce a transient elevation of the intracellular cyclic AMP in human polymorphonuclear cells: a two- to three-fold increase was observed within 1 min after stimulation and approached prestimulation levels by 2 min incubation. These changes in cyclic AMP were not associated with significant changes in cyclic GMP levels. Zymosan caused the release of PAF and beta-glucuronidase and particle uptake, which was initiated about 5 min after stimulation. These results suggest that the transient increase in cyclic AMP content might regulate an early event during mediator release. In an attempt to study further the significance of this rise in cyclic AMP, cells were preincubated with various phosphodiesterase inhibitors. Preincubation of the cells with methylisobutylxanthine (MIX, 10(-6) M to 5 X 10(-5) M), theophylline (3 X 10(-5) to 3 X 10(-3) M) or dipyridamole (10(-6) M to 10(-4) M) enhanced the increase in cyclic AMP levels, but resulted in dose-dependent inhibition of Zc-induced mediator release. Particle uptake and beta-glucuronidase release were less sensitive than PAF release to phosphodiesterase inhibitors, which argues in favour of the independence of both phenomena. Synergistic experiments with MIX and cyclic AMP indicate that the effect of this drug is through its action on cyclic AMP levels. These results suggest that while Zc-induced cyclic AMP elevation might occur in an intracellular place critical to its effect; phosphodiesterase inhibitors may elevate cyclic AMP levels throughout the cell and therefore inhibit the biological response.
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PMID:Modulatory role of cyclic AMP in the release of platelet-activating factor from human polymorphonuclear leucocytes. 627 75

The present study examines the role of cardiac lysosomal enzymes in the pathogenesis of the cardiomyopathy that develops in genetically diabetic C57BL/KsJ db+/db+ mice. Db+/db+ mice and littermate controls were sacrificed as age-matched pairs between 5-26 weeks of age. C57BL/6J ob/ob mice and littermates served as other controls. The hearts were excised, homogenized, and the following enzymatic activities measured: N-Acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucosaminidase, aryl sulphatase, alpha-mannosidase, alpha-glucosidase, beta-galactosidase, beta glucosidase, total p-nitrophenyl phosphatase, acid phosphatase and 5'-phosphodiesterase type IV. There is a progressive decrease in cardiac lysosomal enzyme activities of db+/db+ mice for the period 5-21 weeks of age. All enzyme activity is depressed significantly during the 9-21 week interval with beta-glucuronidase, aryl sulphatase and beta-glucosidase decreased about 40-50%. The decrease in lysosomal enzyme activity can explain the accumulation of large residual bodies and interstitial material in the myocardium of the db+/db+ animals
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PMID:Lysosomal enzymes in experimental diabetic cardiomyopathy. 678 Feb 37

Lysosomes form an integral part of the degradative mechanisms of the phagocytic cells. Mice were injected with suramin, a lysosomotrophic drug, to investigate the effects of lysosomal pathology on the cell biology and in situ bactericidal activity of the pulmonary macrophage. Treatment with suramin resulted in marked alterations in the cell biology of the macrophage: (i) increased vacuolization and protein content, (ii) suppressed intracellular phagosome-lysosome fusion, (iii) decreased activity of the lysosomal enzymes beta-glucuronidase and N-acetyl-glucosaminidase, and (iv) enhanced exocytosis of acid phosphatase during phagocytosis. Addition of suramin, in vitro, to cell lysates resulted in a reduction in the catalytic activities of acid phosphatase, beta-glucuronidase, and N-acetyl-glucosaminidase; thereby suggesting that selective interaction, in vivo, between suramin and lysosomes containing beta-glucuronidase and N-acetyl-glucosaminidase may have occurred. Plasma membrane 5'-nucleotide phosphodiesterase activity was increased in macrophages recovered from suramin-treated animals. Although the "resting-state" reduction of nitroblue tetrazolium (NBT) was lower in these macrophages, cells stimulated by a phagocytic challenge demonstrated normal increases in NBT reduction. Phagocytosis, in vitro, and pulmonary bactericidal activity were not altered. These data demonstrate that suramin altered numerous aspects of the phagocyte's lysosomal system. Despite these changes in the cell biology of the pulmonary macrophage, the cell's defense functions were not reduced.
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PMID:Lung macrophage defense responses during suramin-induced lysosomal dysfunction. 683 43

Polymorphonuclear leucocytes were isolated from pig blood relatively free from other cells and were characterised biochemically and morphologically and compared with human PMNLs. The activities of 16 enzymes of porcine and human PMNLs were measured and compared. Alkaline phosphatase, acid phosphatase, phosphodiesterase, gamma-glutamyl transpeptidase, NADH-cytochrome c oxidoreductase, malate dehydrogenase and acetylcholinesterase had higher specific activities in procine than in human cells. Alkaline phosphatase has an 87-fold higher specific activity in porcine than in human cells. beta-glucuronidase, lysozyme, beta-galactosidase, N-acetyl-glucosaminidase, beta-glucosidase, myeloperoxidase and catalase had higher specific activities in human than in porcine cells. beta-glucuronidase and myeloperoxidase showed over a 1000- and a 13-fold higher specific activity, respectively, in human than in porcine cells. Porcine PMNLs are readily available in large numbers and are recommended for studies of phagocytosis, chemotaxis and membrane biochemistry.
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PMID:Biochemical characterisation of porcine polymorphonuclear leucocytes: comparison with human polymorphonuclear leucocytes. 687 22

Activities of lysosomal hydrolases were measured in the leucocytes of cattle, sheep, goats, horses and pigs. There was high activity of arylsulphatase in leucocytes from cattle, high activities of alpha-fucosidase and beta-glucuronidase in leucocytes from horses and high activity of acid phosphatase in granulocytes from pigs. Within species, arylsulphatase and beta-galactosidase activities were higher in granulocytes than in mononuclear cells, but beta-glucuronidase, phosphodiesterase and alpha-galactosidase activities were higher in mononuclear cells than in granulocytes. Eosinophils of cattle, sheep, goats and horses contained at least 10 times the activity of alpha-mannosidase and arylsulphatase found in neutrophils. For most of the other enzymes studied, there were differences in cattle and goats but not in sheep, horses or pigs between their specific activities in neutrophils and eosinophils.
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PMID:Lysosomal hydrolase activity in leucocytes from cattle, sheep, goats, horses and pigs. 715 6

The protein concentration in bile from several species is reported. The changes in output of protein, bile salts and several enzymes have been followed in rat bile over a 48 h cannulation period. Bile-salt concentration dropped rapidly owing to interruption of the enterohepatic circulation but the output of protein, lysosomal enzymes [acid phosphatase (EC 3.1.3.2) and beta-D-glucuronidase (EC 3.2.1.31)] and plasma-membrane enzymes [5'-nucleotidase (EC 3.1.3.5) and phosphodiesterase I (EC 3.1.4.1)] was maintained. Liver cell damage, monitored by output of lactate dehydrogenase, was very low throughout. Protein, lysosomal enzymes and plasma-membrane enzymes showed different patterns of output with time, but all showed a net increase between 12 and 24 h. The output of lysosomal and plasma-membrane enzymes was between 1 and 5% of the total liver complement over the first 24 h; if inhibition by biliary components is taken into account the output of some of these enzymes, particularly acid phosphatase, may be greater. Ultracentrifugation of bile showed that as the concentration of bile salts decreases the proportion of plasma-membrane enzymes in a sedimentable form increases. The results are discussed in relation to other studies of biliary proteins and to studies of the perturbation of membranes and cells with bile salts.
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PMID:Enzymes and proteins in bile. Variations in output in rat cannula bile during and after depletion of the bile-salt pool. 730 64

Polymorphonuclear cells (PMN) are the dominating inflammatory cell population in acute tissue injury and contribute to host-defence mechanisms by formation and release of chemical mediators. The aim of the present study was to investigate whether chemoattractant-induced PMN stimulation can be synergistically antagonized by vasodilatory prostaglandins and nitric oxide (NO), both being formed by the vasculature in inflamed areas. PGE1 (10 nM-10 microM) inhibited concentration-dependently formyl-methionyl-leucyl-phenylalanine (fMLP)-induced beta-glucuronidase and oxygen radical (O2.) release from human PMN. The NO donor linsidomine (100 microM) was ineffective, but significantly enhanced PGE1 effects on oxygen radical generation and enzyme release. The non-selective phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) (0.5 mM) potentiated PGE1 effects on all parameters measured. The combination linsidomine (100 microM) plus IBMX (0.5 mM) did not additionally reduce beta-glucuronidase release, but abolished fMLP-stimulated O2. generation. There was a stimulation of cAMP formation by PGE1 but not by linsidomine, both in the absence and presence of IBMX. It is concluded that the effects of linsidomine on PMN function and its synergism with PGE1 are not tightly correlated with total cAMP accumulation. Alternatively, the inhibition of O2. generation by linsidomine may be related to its ability to modulate the activation of the NADPH oxidase system or to scavenge free oxygen radicals.
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PMID:Synergistic inhibition of human polymorphonuclear function by prostaglandin E1 and linsidomine. 886 34

3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a novel type of soluble guanylyl cyclase (sGC) activator, is useful in investigating the signaling of cGMP and may provide a new approach for treating cardiovascular diseases. Herein, YC-1 was demonstrated to inhibit the generation of superoxide anion (O2-) and the release of beta-glucuronidase release, to diminish the membrane-associated p47phox and to accelerate resequestration of cytosolic calcium in formyl-l-methionyl-l-leucyl-l-phenylalanine-activated human neutrophils. YC-1 not only directly promoted sGC activity and cGMP formation but also dramatically potentiated sodium nitroprusside-induced sGC activity and cGMP formation in human neutrophils. However, the synergistic increase in the amount of cGMP was inconsistent with its cellular response. Moreover, neither an sGC inhibitor nor protein kinase G inhibitors reversed the inhibitory effect of YC-1. Interestingly, YC-1 also increased the cAMP concentration and protein kinase (PK)A activity. The inhibitory effect of YC-1 was significantly enhanced by prostaglandin (PG)E1 and isoproterenol, and almost abolished by PKA inhibitors. These results show that cAMP, but not cGMP, mediates the YC-1-induced inhibition of human neutrophils. YC-1 increased the PGE1- and forskolin-induced but not 3-isobutyl-1-methylxanthine-produced cAMP formation, suggesting inhibition of phosphodiesterase. These findings thus reveal novel mechanism-mediated anti-inflammatory properties of YC-1 in human neutrophils, which can influence the progression of cardiovascular disease. cAMP, but not cGMP, plays an important role in the regulation of respiratory burst and degranulation in human neutrophils.
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PMID:Soluble guanylyl cyclase activator YC-1 inhibits human neutrophil functions through a cGMP-independent but cAMP-dependent pathway. 1464 72


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