Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+ antagonists such as nifedipine (Nif) inhibit processes that depend on extracellular Ca2+ in many muscular and secretory cells. The effect of Nif on mediator release and Ca2+ uptake by human polymorphonuclear neutrophils (PMN) has been investigated. Nif caused a concentration-dependent inhibition of the Ca2+ ionophore-induced release of platelet-activating factor (PAF-acether), slow-reacting substance (SRS) and to a lesser degree beta-glucuronidase (beta-glu). Nif inhibited the synthesis of PAF-acether rather than its release. Increasing Ca2+ concentration in the bathing medium from 1.3 to 2.8 mM completely reversed the effect of Nif on PAF-acether secretion. Nif at 1 and 5 microM reduced PMN45Ca2+ uptake induced by the Ca2+ ionophore A 23187. These results indicate that the inhibition by Nif of mediator release depends probably on the Ca2+-antagonistic property of the drug. A preliminary ex vivo study suggests that this inhibitory effect on neutrophil functions exists during therapeutic use.
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PMID:Effect of the Ca2+ antagonist nifedipine on the release of platelet-activating factor (PAF-acether), slow-reacting substance and beta-glucuronidase from human neutrophils. 613 31

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 effect of totally synthetic PAF-acether (1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine), 2-lyso PAF-acether (1-O-octadecyl-sn-glyceryl-3-phosphorylcholine) and lyso-phosphatidylcholine on enzyme release and superoxide production from human polymorphonuclear neutrophils (PMN were studied. PMN (2 X 10(6) ml-1) were incubated at 37 degrees C with various concentrations of phospholipids in the absence of cytochalasin B. At 10(-7) M, PAF-acether induced superoxide production and beta-glucuronidase, acid phosphatase and lysosyme release, but not that of cytoplasmic lactic dehydrogenase. In the same condition 2-lyso PAF-acether and lyso-phosphatidylcholine were ineffective. In the presence of phagocytic stimuli PAF-acether enhanced in the range from 10(-7) M to 10(-10) M the enzyme release and only at 10(-7) M the superoxide production. Thus, the capacity of PAF-acether to stimulate PMN, as well as platelet function, indicates a prominent role for this lipid mediator in inflammatory processes.
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PMID:Platelet-activating factor (PAF-acether), an activator of neutrophil functions. 629 78

Synthetic 1-O-alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (PAF) and 1-O-alkyl-sn-glyceryl-3-phosphorylcholine (lyso-PAF) have previously been shown to induce chemotaxis and chemokinesis of human neutrophils. We present here data showing that these agents are inactive by themselves, but that they enhance neutrophil secretion once it has been initiated by a calcium ionophore or by zymosan. Two substances, the lipid eosinophil chemotactic factor (ECF) and the lysosomal enzyme beta-glucuronidase, are used as markers for neutrophil release. PAF augments secretion of both substances in a dose-dependent fashion, with lyso-PAF being less potent. The kinetics of enhancement are very rapid (less than 2 min) and are not reversible by washing of the cells. A pyrazoline derivative that inhibits arachidonate cyclo-oxygenation and lipoxygenation, reduces the enhancing effect of PAF and lyso-PAF. PAF, and less so lyso-PAF, are thus potentially important modulators of neutrophil secretion during inflammatory processes.
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PMID:Effect of platelet activating factor on leukocytes. II. Enhancement of eosinophil chemotactic factor and beta-glucuronidase release. 681 73

Synthetic PAF-acether was studied for its effect on human neutrophil migration and secretion. Based on checkerboard analysis, the factor is chemokinetic for neutrophils, but it also enhances ECF-stimulated chemotaxis. By itself, PAF-acether does not induce ECF or beta-glucuronidase secretion from neutrophils, but it causes a dose-dependent enhancement of release in the presence of zymosan. PAF-acether thus potentially modulates neutrophil functions during inflammatory events.
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PMID:Effect of synthetic PAF-acether on human neutrophil function. 704 68

We studied the effects of polymorphonuclear leukocytes (PMNLs) activated by N-formyl-methionyl-leucyl-phenylalanine on the endothelium-dependent relaxation of the rabbit basilar artery (BA). In the presence of activated PMNLs the maximal vessel relaxation to acetylcholine (ACh) and bradykinin (endothelium-dependent dilators) was decreased from 62 +/- 7 and 48 +/- 6% to 23 +/- 9 and 19 +/- 7, respectively, (p < 0.05). The endothelium-independent relaxation to nitroprusside was not affected by PMNLs. When PMNLs were activated in the organ chamber in the presence of a low concentration of platelet-activating factor (PAF, 10(-10) mol/l), the depression of ACh- and bradykinin-induced relaxation increased by 27 +/- 9 and 23 +/- 7%, respectively (p < 0.05), though at this concentration PAF alone did not cause PMNLs to induce endothelial dysfunction. In addition, in the presence of PAF, activated PMNLs inhibited endothelium-dependent relaxation at lower cell concentrations and shorter periods of contact with the endothelium. PMNL effects on the endothelium were correlated with the level of cell exocytosis as tested by accumulation of beta-glucuronidase activity. In the presence of PAF, accumulation of this activity increased from 46 +/- 6 to 79 +/- 8 U/ml (p < 0.05). Examination of BA segments by scanning electron microscopy revealed that, after the treatment with activated PMNLs, the endothelium was morphologically preserved, but in the presence of PAF PMNLs caused more apparent microlesions in the endothelial layer. We conclude that small quantities of PAF potentiate the activation of marginated PMNLs. These cells then become more aggressive towards the endothelium, producing significant depression of the endothelium-dependent relaxation.
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PMID:Leukocyte-induced endothelial dysfunction in the rabbit basilar artery: modulation by platelet-activating factor. 755 83

Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), or platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down-regulate C5a-dependent neutrophil functions. When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a-stimulated beta-glucuronidase release and chemotaxis could be observed, whereas FMLP-, IL-8-, LTB4- or PAF-dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High-performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a-dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, beta-glucuronidase release, and chemotaxis were also specifically inhibited. Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down-regulation of acute inflammation.
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PMID:Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis. 1514 22

Five new Diels-Alder type adducts, mongolicins A - E, and nine known compounds, mongolicin F, chalcomoracin, mulberrofuran T, mulberrofuran G, mulberrofuran F, albanol B, kuwanon O, mulberrofuran H and kuwanon H, were isolated from the stem and root bark of Morus mongolica. Their structures were determined by spectroscopic analysis and chiroptical methods. Among them, compounds and showed potent anti-inflammatory activities (inhibition of release of beta-glucuronidase from rat PMNs induced by PAF) with inhibitory ratios of 80.4% (P<0.05) and 77.0% (P<0.001) at a concentration of 10(-5) mol L-1. Compounds and were active as antioxidatives (inhibition of liver microsomal lipid peroxidation induced by Fe2+-Cys system) with inhibitory ratios of 83.6% (P<0.05), 86.0% (P<0.05), and 63.0% (P<0.05) at a concentration of 10(-5) mol L-1.
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PMID:Five new diels-alder type adducts from the stem and root bark of Morus mongolica. 1645 Feb 96

A series of aromatic aminoketones were synthesized by Mannich reaction. Structures of these compounds were confirmed by 1H NMR, MS and HRMS or element analysis. Pharmacological screening showed that most target compounds inhibited the release of beta-glucuronidase in polymorphonuclear leucocytes by PAF (platelet activating factor) and compounds MA12, MA13, MA18, MA21 and MA33 were more active. The study suggests that target compounds are potential PAF receptor antagonists and their anti-inflammatory activities are due to the inhibition of release of lysosomal enzyme.
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PMID:[Synthesis and antiinflammation activity of aromatic aminoketone compounds, a new type of PAF-receptor antagonist]. 1904 82


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