Paracetamol-induced stimulation of glycogenolysis in isolated mouse hepatocytes is not directly associated with cell death.
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.
Burcham
P C
PC
Department of Pharmacology, University of Western Australia, Nedlands.
Harman
A W
AW
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
D008112:Liver Glycogen; C000939:2,4-dichloro-6-phenylphenoxyethylamine; D000082:Acetaminophen; D011078:Polychlorinated Biphenyls; D010762:Phosphorylase a; D000111:Acetylcysteine