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)

To clarify the mechanism of irreversible myocardial damage, we studied the relationship between ischaemic mitochondrial dysfunction and leakage of lysosomal enzymes, and the effects of propranolol on myocardial damage. Open chest anaesthetised dogs were divided into six groups: 30 min occlusion of the left anterior coronary artery (LAD); 2 h LAD occlusion; 2 h LAD occlusion after premedication with 0.3 mg.kg-1 propranolol; 30 min LAD occlusion/l h reperfusion; 2 h LAD occlusion/l h reperfusion; and 2 h LAD occlusion/l h reperfusion after propranolol premedication. After occlusion or reperfusion, heart mitochondria were prepared from normal and occluded or reperfused areas, and mitochondrial function (rate of oxygen consumption in State III, and respiratory control index) was measured polarographically. Myocardial tissue was fractionated and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured. Electron microscopic studies were performed. Thirty min occlusion induced mitochondrial dysfunction without leakage of lysosomal enzymes. Reperfusion for 1 h reversed these changes. However occlusion for 2 h induced mitochondrial dysfunction associated with the leakage of lysosomal enzymes, and mitochondrial dysfunction was not reversed by 1 h reperfusion. Propranolol reduced mitochondrial dysfunction after 2 h occlusion and prevented leakage of lysosomal enzymes. Mitochondrial function was fairly well maintained after 1 h reperfusion in dogs premedicated with propranolol. Structural changes in mitochondria were observed in the 2 h occlusion/l h reperfusion group, and were reduced by premedication with propranolol. These results suggest that irreversible injury of ischaemic mitochondria is closely linked with instability of lysosomal membranes, and that propranolol prevented irreversible myocardial mitochondrial dysfunction.
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PMID:Biochemical and morphological changes in myocardium during coronary occlusion and reperfusion in canine hearts: effects of propranolol on myocardial damage. 261 9

The influence of autonomic neurohormones on the immunologic release of beta-glucuronidase (EC 3.2.1.31) from, and the cyclic nucleotide levels in, human neutrophils was determined. Interaction of neutrophils with rheumatoid arthritic, serum-treated zymosan particles in a neutral balanced salt solution at 37 degrees resulted in the extracellular discharge of beta-glucuronidase without any loss of cell viability, as indicated by the failure of incubated cells to take up eosin Y or to release cytoplasmic lactate dehydrogenase (EC 1.1.1.27). Epinephrine reduced the release of beta-glucuronidase from neutrophils in the presence of zymosan during 2-30 min of incubation and elicited a concomitant elevation of adenosine 3':5'-monophosphate levels. Propranolol, a beta-adrenergic receptor antagonist, but not phentolamine, an alpha-adrenergic receptor antagonist, blocked both actions of epinephrine. Acetylcholine stimulated the release of beta-glucuronidase, but not lactate dehydrogenase, and provoked a concomitant elevation of guanosine 3':5'-monophosphate levels. Atropine, a muscarinic receptor antagonist, but not hexamethonium, a ganglionic blocker, inhibited both actions of acetylcholine. Interaction of neutrophils and zymosan particles resulted in an elevation of guanosine 3':5'-monophosphate levels within 2 min. These data suggest that intracellular guanosine 3':5'-monophosphate may be involved in mediating the immunologic release of lysosomal enzymes from human neutrophils whereas adenosine 3':5'-monophosphate may inhibit enzyme release. Moreover, autonomic neurohormones appear to be capable of modulating lysosomal enzyme release by virtue of their capacity to elevate neutrophil cyclic nucleotide levels.
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PMID:Hormonal control of lysosomal enzyme release from human neutrophils: elevation of cyclic nucleotide levels by autonomic neurohormones. 415 56

The complete metabolic fate of propranolol has been difficult to assess because of its complexity. The aim of this study was therefore to develop an analytical approach that would permit separation and quantitation of all major propranolol metabolites. This was accomplished in the urine of dogs, rats, and hamsters using a combination of techniques. Propranolol, 25 mg/kg, was given together with [3H]propranolol po to dogs and ip to rats and hamsters. After hydrolysis with beta-glucuronidase and sulfatase, the 0-24-hr urine was extracted with diethyl ether first at pH 9.6 to yield basic, phenolic, and neutral metabolites. This fraction contained 35 +/- 1% (mean +/- SE; N = 3) in the dog, 59 +/- 2% in the rat, and 53 +/- 5% in the hamster (based on the total radioactivity in urine). The urine was then extracted at pH 2 for acidic metabolites, yielding 32 +/- 3% in the dog, 4 +/- 1% in the rat, and 5 +/- 1% in the hamster. The pH 9.6 and pH 2 extracts were each separated into its components by HPLC. Liquid scintillation spectrometry and GC/MS allowed quantitation and identification of about 15 phase I metabolites. Major species differences existed, with glucuronidation and side chain oxidation dominating in the dog and ring oxidation in the rat and hamster. A large nonextractable fraction constituting previously unrecognized propranolol metabolites was discovered both in dogs (34 +/- 2%) and in rats (37 +/- 1%) and hamsters (40 +/- 8%). This fraction, which appeared to have a long half-life in the dog and rat, could be separated by HPLC into several distinct radioactive peaks. Preliminary attempts to identify these metabolites, which differed among species, indicated them to be highly polar and labile, some of them probably conjugates of known ring-hydroxylated metabolites.
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PMID:Quantitative metabolic fate of propranolol in the dog, rat, and hamster using radiotracer, high performance liquid chromatography, and gas chromatography-mass spectrometry techniques. 613 86

We studied the degranulation reaction of electropermeabilized human neutrophils induced by 1,2-didecanoyl-3-sn-phosphatidic acid (PA10). PA10 dose-dependently induced the release of beta-glucuronidase, an enzyme of azurophil granules, but did not induce the release of lactoferrin, a protein of specific granules. The enzyme release by PA10 absolutely required Ca2+, ATP, and Mg2+ and the concentrations for the half-maximal response were 2.5 microM, 60 microM, and 0.25 mM, respectively. Although Ca2+ alone at concentrations higher than 10 microM induced the release of both beta-glucuronidase and lactoferrin, the extents of the release were far less than that of the beta-glucuronidase release by PA10. Phorbol myristate acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol induced the release of lactoferrin alone at concentrations of Ca2+ below 0.5 microM while they induced the release of both beta-glucuronidase and lactoferrin at higher Ca2+ concentrations, indicating that the degranulation induced by PA10 is not mediated by diacylglycerol which might be formed from PA. The degranulation reactions induced by PA10 and PMA were dose-dependently inhibited by staurosporine and calphostin C, protein kinase C inhibitors, although no direct activation of protein kinase C by PA10 was observed. The extent of the beta-glucuronidase release by PA10 was not enhanced by the addition of PMA. Propranolol, which inhibits protein kinase C as well as phosphatidic acid phosphohydrolase, strongly inhibited the degranulation reactions induced by PA10 and PMA. Ethanol, a metabolic modulator of phospholipase D, and cyclic AMP did not affect the degranulation reactions by PMA and PA10.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphatidic acid induces the release of beta-glucuronidase but not lactoferrin from electropermeabilized human neutrophils. 820 72