title: Paracetamol-induced stimulation of glycogenolysis in isolated mouse hepatocytes is not directly associated with cell death.
abstract: Paracetamol intoxication in vivo is known to be accompanied by depletion of hepatic glycogen stores. We have demonstrated a dose-dependent stimulation of glycogenolysis by paracetamol in glycogen-rich hepatocytes isolated from the mouse. Concentrations of paracetamol that produced plasma membrane damage were also found to activate glycogen phosphorylase a and deplete cellular glycogen contents. However, paracetamol-mediated stimulation of glycogenolysis could be dissociated from the events associated with paracetamol-induced cell killing. Both N-acetylcysteine and 2,4-dichloro-6-phenylphenoxyethylamine markedly reduced the extent of hepatocellular plasma membrane damage induced by paracetamol, yet neither agent prevented the activation of phosphorylase a nor the depletion of glycogen. These findings suggest that the hepatic glycogen depletion that accompanies paracetamol intoxication in vivo is due, at least in part, to a direct effect of the drug on the liver.
authors.affiliation: Department of Pharmacology, University of Western Australia, Nedlands.
authors.forename: P C
authors.initials: PC
authors.lastname: Burcham
authors.forename: A W
authors.initials: AW
authors.lastname: Harman
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D051379:Mice; D010762:Phosphorylase a / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D013997:Time Factors
chemical_list: D008112:Liver Glycogen; C000939:2,4-dichloro-6-phenylphenoxyethylamine; D000082:Acetaminophen; D011078:Polychlorinated Biphenyls; D010762:Phosphorylase a; D000111:Acetylcysteine