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

The effect of diphenylhydantoin (DPH) on mouse calvarial bone metabolism was studied in vitro. DPH caused a dose-dependent, reversible inhibition of PTH and PGE2-stimulated bone resorption at concentrations above 20-30 micrograms/ml without affecting cyclic AMP formation. The inhibition was observed already after 60 min and was accompanied by a reduced release of the lysosomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase. The calcium antagonist Verapamil had similar effects on bone resorption and lysosomal enzyme release and it is suggested that DPH influences bone resorption by interfering with calcium fluxes across osteoclastic cell membranes resulting in low intracellular calcium levels and reduced exocytotic processes.
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PMID:Diphenylhydantoin inhibits parathyroid hormone and prostaglandin E2-stimulated bone resorption in mouse calvaria without affecting cyclic AMP formation. 299 25

The working hypothesis of many studies of shock has been that naloxone acts by blocking centrally and/or peripherally located opioid receptors. At plasma concentrations used to treat experimental shock (10(-6) M and above), naloxone inhibited the in vitro release of superoxide (O2-) by human neutrophils that were stimulated by the E. coli peptide N-formyl methionyl leucyl phenylalanine (FMLP). Superoxide release stimulated by phorbol 12,13-dibutyrate (PDB) was also inhibited by naloxone. Naloxone had no effect on the FMLP-stimulated release of beta-glucuronidase or lysozyme. Naloxone had no effect on 3H FMLP receptor binding. Studies utilizing 3H naloxone revealed the presence of a ligand-specific naloxone binding site on human neutrophils with a Kd of 1.2 X 10(-5) M, which is close to the ID50 of the inhibitory effect upon O2- release (1.8 X 10(-5). Thyrotropin releasing factor (TRF) had no effect upon 3H naloxone binding or on O2- release. Verapamil, a calcium channel blocker, inhibited 3H naloxone binding, and O2- release while nifedipine, another calcium channel blocker had no effect on either assay except at 10(-4) M, at which concentration 3H naloxone binding as well as the release of O2- were increased. These experiments suggest that the inhibitory effect of naloxone upon O2- release is mediated via a specific binding site.
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PMID:Inhibition by naloxone of neutrophil superoxide release: a potentially useful antiinflammatory effect. 302 81

The rabbit polymorphonuclear neutrophil degranulation response to 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine depends on extracellular calcium. In the absence of this bivalent cation, neutrophil suspensions pretreated with cytochalasin B responded to the lipid by releasing minimal amounts of lysozyme and beta-glucuronidase. Incremental increases in extracellular calcium over a range of 20-200 microM led to increasing amounts of lipid-stimulated enzyme release. In contrast, extracellular magnesium neither supported nor enhanced the degranulation responses. Verapamil (25-200 microgram/ml), a calcium channel blocker, inhibited degranulation. Neutrophil suspensions exposed to the phosphocholine stimulus rapidly took up radiolabeled extracellular calcium. The kinetics of this calcium uptake were similar to the kinetics of enzyme release, and the amount of calcium taken up correlated closely with the amount of released lysozyme and beta-glucuronidase. Finally, in a dosage which blocked degranulation, verapamil inhibited calcium uptake. Thus, the rapid association of extracellular calcium with the neutrophil may mediate, at least in part, the degranulating actions of the phosphocholine stimulus.
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PMID:Role of extracellular calcium and neutrophil degranulation responses to 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine. 627 Oct 16

The present investigation addressed the role of verapamil for oral pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1) verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1) morphine-hydrochloride) were also employed. Oral bioavailability of M6G and the fraction of M6G deglucuronidated to morphine were estimated from areas under the plasma-concentration vs. time curves (AUC) of morphine and its glucuronides. As initial results pointed towards inhibition of glucuronidases by verapamil, its capability to specifically inhibit E. coli and/or rat intestinal beta-glucuronidase was assessed using altered cleavage of the model substrate 4-methylumbelliferyl-beta-D-glucuronide (MUG). Oral bioavailability of M6G was 2.1%; 13% of oral M6G was deglucuronidated to morphine. Co-administration of verapamil did not increase the AUC of M6G. AUCs of morphine and morphine-3-glucuronide were smaller in the verapamil group than in controls. Verapamil co-administration decreased the fraction of M6G deglucuronidated to morphine to 4.6%. In vitro experiments provided evidence that verapamil inhibits beta-glucuronidase from E. coli with an IC(50) of 30 microM, whereas no inhibition of the rat beta-glucuronidase from small intestine was seen. In conclusion, verapamil decreased intestinal deglucuronidation of M6G by inhibiting E. coli beta-glucuronidase. This indicates that verapamil is not suited as P-gp inhibitor in experiments involving glucuronides. An increase in the intestinal absorption of M6G due to P-gp-inhibition was not observed at the verapamil dose studied.
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PMID:Verapamil decreases glucuronidase activity in the gut. 1199