Effects of mushroom toxins on glycogenolysis; comparison of toxicity of phalloidin, alpha-amanitin and DL-propargylglycine in isolated rat hepatocytes.
The effects of phalloidin and alpha-amanitin as toxins of Amanita species and DL-propargylglycine identified from A. abrupta on the glycogenolysis in isolated rat hepatocytes were investigated. Phalloidin decreased glycogen content and activated phosphorylase a activity remarkably. alpha-Amanitin also decreased glycogen content significantly but activated phosphorylase a activity slightly. DL-Propargylglycine slightly affected glycogenolysis. Phalloidin, which most affected glycogenolysis among the three compounds mentioned above, elevated cytosolic Ca2+ concentration ([Ca2+]i) and 45Ca uptake into cells. Phalloidin depressed slightly 3H-inositol incorporation into phosphatidylinositol (PI) and remarkably phosphatidylinositol 4,5-bisphosphate (PIP2) but increased phosphoinositides breakdown. These results suggest that phalloidin alters phosphoinositides turnover and intracellular Ca2+ homeostasis, subsequently activates phosphorylase a, resulting in glycogenolysis in isolated rat hepatocytes.
Kawaji
A
A
Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Yamauchi
K
K
Fujii
S
S
Natsuki
R
R
Takabatake
E
E
Yamaura
Y
Y
D000480:Alkynes; D000546:Amanitins / Q000633:toxicity*; D000818:Animals; D001487:Basidiomycota / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D002478:Cells, Cultured; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity; D006003:Glycogen / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010293:Pargyline / Q000031:analogs & derivatives* / Q000633:toxicity; D010590:Phalloidine / Q000633:toxicity*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014118:Toxins, Biological / Q000633:toxicity*
D000480:Alkynes; D000546:Amanitins; D002413:Cations, Divalent; D010716:Phosphatidylinositols; D014118:Toxins, Biological; D010590:Phalloidine; D007294:Inositol; C009055:propargylglycine; D006003:Glycogen; D010293:Pargyline; D002118:Calcium; D005998:Glycine