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)

The action of PGD2 and its mimetic ZK 110.841 ((5Z,13E)-(9R,11R,15S)-9-chloro-15-cyclohexyl-11,15- dihydroxy-16,17,18,19, 20-pentanor-5,13-prostadienoic acid) was compared to PGE1 in vitro on superoxide anion generation, degranulation, leukotriene (LT) B4 release and Ca++ fluxes in human polymorphonuclear leukocytes (PMN). All compounds were potent inhibitors of formyl-methionyl-leucyl-phenylalanine (FMLP)- and platelet-activating factor (PAF)-induced superoxide anion generation, beta-glucuronidase release and Ca++ influx. The PAF-induced release of LTB4 in the presence of 10 mumoles/l arachidonic acid was significantly attenuated by these prostaglandins. This inhibition of PMN function was paralleled by an increase in cellular cAMP levels. The molar potency of the prostaglandins used was comparable, although the D-type compounds appeared slightly more potent in some PMN function tests. None of the substances affected PMN activation induced by the calcium inophore calcimycin (A23187). The data demonstrate an effective inhibition of receptor-mediated (FMLP, PAF) PMN activation by PGD2 and its mimetic ZK 110.841, suggesting either an inhibitory PGD2 receptor on human PMN or action of PGD2 at the PGE receptor. PGD2 is a labile compound in vivo and is rapidly metabolized into a number of products with different biological properties. Since ZK 110.841 lacks this instability, this compound may serve as an important tool to classify PGD2-mediated reactions.
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PMID:PGD2 and its mimetic ZK 110.841 are potent inhibitors of receptor-mediated activation of human neutrophils. 164 6

Among the many possible mediators of the early asthmatic response, prostaglandin D2, a bronchoconstrictor, is the principal cyclooxygenase metabolite of arachidonic acid that is released upon the activation of mast cells and is also synthesized by human alveolar macrophages. We performed bronchoalveolar lavage in five patients with chronic stable asthma, before and up to nine minutes after local provocative challenge with Dermatophagoides pteronyssinus. The lavage fluid was analyzed for products of arachidonic acid metabolism. Prostaglandin D2 levels in all five patients rose an average of 150-fold, from less than 8 to 332 +/- 114 pg per milliliter (mean +/- SEM; P less than 0.050), after local instillation of the antigen. Levels of 15-hydroxyeicosatetraenoic acid, which may also have a role in the pulmonary allergic response, were detectable in lavage fluid before challenge and increased after provocation with the antigen in four of the five patients. The activity of beta-glucuronidase, an enzyme released by macrophages and mast cells upon stimulation, tended to increase in the lavage fluid after provocation in all patients. These studies provide evidence that the release of prostaglandin D2 into the airways is an early event after the instillation of D. pteronyssinus in patients who are sensitive to this antigen.
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PMID:Release of prostaglandin D2 into human airways during acute antigen challenge. 346 6

The cultured mouse macrophage-like cell line Mm-1 synthesizes and secretes lysozyme continuously like normal macrophages. Culture of the cells in the presence of prostaglandin D2 for 3 days strongly inhibited their production of lysozyme activity. Prostaglandin D2 caused dose-dependent inhibition of the activity: 1 X 10(-6) M prostaglandin D2 caused about 50% inhibition. Inhibition by prostaglandin D2 was not related to cytotoxicity and was reversible. The rate of synthesis of lysozyme protein was measured by culturing Mm-1 cells with radioactive amino acids and then immunoprecipitating the protein. At the concentrations used, prostaglandin D2 inhibited the synthesis of lysozyme dose-dependently, but did not suppress the synthesis of total protein. Of the various types of prostaglandin, only prostaglandin D2 inhibited the production of lysozyme in Mm-1 cells. Moreover, prostaglandin D2 did not inhibit the production of other lysosomal enzymes, such as acid proteinase, acid phosphatase and beta-glucuronidase, and did not affect Fc receptors on the cell surface, adherence of cells to the culture dish or the cell morphology. These results indicate that prostaglandin D2 specifically inhibits the synthesis of lysozyme in Mm-1 cells. When Mm-1 cells were cultured for 3 days in the presence of the ethyl acetate extract from the culture medium in which Mm-1 cells had been cultured with prostaglandin D2 for 3 days, the production of lysozyme activity of Mm-1 cells was also markedly inhibited by the extract. After the incubation of prostaglandin D2 for 3 days with Mm-1 cells, less than 10% of the initial prostaglandin D2 remained and two major metabolites appeared. These results suggest that the metabolites of prostaglandin D2 were involved in the inhibitory action of prostaglandin D2 in Mm-1 cells.
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PMID:Specific inhibition by prostaglandin D2 and its metabolites of lysozyme synthesis in mouse macrophage-like cell line, Mm-1. 385 62