Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12934
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dc.contributor.authorSewell, Richard Ben
dc.contributor.authorGrinpukel, S Aen
dc.contributor.authorZinsmeister, A Ren
dc.contributor.authorLaRusso, N Fen
dc.date.accessioned2015-05-16T02:41:51Z
dc.date.available2015-05-16T02:41:51Z
dc.date.issued1988-10-01en
dc.identifier.citationGastroenterology; 95(4): 1088-98en
dc.identifier.govdoc3137115en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/12934en
dc.description.abstractHepatocyte lysosomes disassemble materials derived from intracellular sources, including lipid-containing membranes, by a process called autophagy. In addition, hepatocyte lysosomes can release their contents into bile by exocytosis. Therefore, using both in vivo and in vitro models, we tested the hypothesis that acute pharmacologic induction of autophagy would modify the biliary excretion of lysosomal protein and of lipids. We treated rats with a single dose of chloroquine (10 mg/kg), glucagon (1 mg/kg), or control solutions and collected bile via bile fistulas. Both chloroquine and glucagon immediately caused a marked and parallel decrease in biliary excretion of three lysosomal enzymes, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and beta-galactosidase, to 25%-30% of baseline values (p less than 0.01). This decrease was sustained for 2 h after glucagon and 4 h after chloroquine administration. In contrast, biliary lipid changes were minor: a slight lowering of biliary cholesterol secretion after chloroquine (p less than 0.05), but no change in biliary bile acids, cholesterol, and phospholipid secretion after glucagon. Changes in biliary excretion of lysosomal enzymes accompanying chloroquine and glucagon administration were associated with morphologic evidence of autophagy as assessed by electron microscopy and by increased fragility of hepatic lysosomes as assessed by latency of N-acetyl-beta-glucosaminidase. These in vivo changes in biliary lysosomal enzyme excretion induced by chloroquine and glucagon were confirmed in vitro using the isolated perfused rat liver. Thus, acute induction of autophagy results in conservation of hepatic lysosomal protein and has virtually no effect on biliary lipid excretion.en
dc.language.isoenen
dc.subject.otherAcetylglucosaminidase.metabolismen
dc.subject.otherAnimalsen
dc.subject.otherBile.metabolismen
dc.subject.otherBile Acids and Salts.metabolismen
dc.subject.otherChloroquine.pharmacologyen
dc.subject.otherCholesterol.metabolismen
dc.subject.otherGalactosidases.metabolismen
dc.subject.otherGlucagon.pharmacologyen
dc.subject.otherGlucuronidase.metabolismen
dc.subject.otherHexosaminidases.metabolismen
dc.subject.otherInsulin.pharmacologyen
dc.subject.otherLiver.drug effects.enzymology.ultrastructureen
dc.subject.otherLysosomes.drug effects.enzymology.ultrastructureen
dc.subject.otherMaleen
dc.subject.otherRatsen
dc.subject.otherRats, Inbred Strainsen
dc.subject.otherbeta-Galactosidase.metabolismen
dc.titlePharmacologic perturbation of rat liver lysosomes: effects on release of lysosomal enzymes and of lipids into bile.en
dc.typeJournal Articleen
dc.identifier.journaltitleGastroenterologyen
dc.identifier.affiliationDepartment of Medicine, Austin Hospital, Heidelberg, Australiaen
dc.description.pages1088-98en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/3137115en
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