Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12934
Title: Pharmacologic perturbation of rat liver lysosomes: effects on release of lysosomal enzymes and of lipids into bile.
Authors: Sewell, Richard B;Grinpukel, S A;Zinsmeister, A R;LaRusso, N F
Affiliation: Department of Medicine, Austin Hospital, Heidelberg, Australia
Issue Date: 1-Oct-1988
Citation: Gastroenterology; 95(4): 1088-98
Abstract: Hepatocyte 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.
Internal ID Number: 3137115
URI: http://ahro.austin.org.au/austinjspui/handle/1/12934
URL: http://www.ncbi.nlm.nih.gov/pubmed/3137115
Type: Journal Article
Subjects: Acetylglucosaminidase.metabolism
Animals
Bile.metabolism
Bile Acids and Salts.metabolism
Chloroquine.pharmacology
Cholesterol.metabolism
Galactosidases.metabolism
Glucagon.pharmacology
Glucuronidase.metabolism
Hexosaminidases.metabolism
Insulin.pharmacology
Liver.drug effects.enzymology.ultrastructure
Lysosomes.drug effects.enzymology.ultrastructure
Male
Rats
Rats, Inbred Strains
beta-Galactosidase.metabolism
Appears in Collections:Journal articles

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