Inhibition by 2-deoxyglucose and 1,5-gluconolactone of glycogen mobilization in astroglia-rich primary cultures.
The presence of glycogen in astroglia-rich primary cultures derived from the brains of newborn rats depends on the availability of glucose in the culture medium. On glucose deprivation, glycogen vanishes from the astroglial cultures. This decrease of glycogen content is completely prevented if 2-deoxyglucose in a concentration of > 1 mM or 1,5-gluconolactone (20 mM) is present in the culture medium. 2-Deoxyglucose itself or 3-O-methylglucose, a glucose derivative that is not phosphorylated by hexokinase, does not reduce the activity of glycogen phosphorylase purified from bovine brain or in the homogenate of astroglia-rich rat primary cultures. In contrast, deoxyglucose-6-phosphate strongly inhibits the glycogen phosphorylase activities of the preparations. Half-maximal effects were obtained at deoxyglucose-6-phosphate concentrations of 0.75 (phosphorylase a, astroglial culture), 5 (phosphorylase b, astroglial culture), 2 (phosphorylase a, bovine brain), or 9 mM (phosphorylase b, bovine brain). Thus, the block of glycogen degradation in these cells appears to be due to inhibition of glycogen phosphorylase by deoxyglucose-6-phosphate rather than deoxyglucose itself. These results suggest that glucose-6-phosphate, rather than glucose, acts as a physiological negative feedback regulator of the brain isoenzyme of phosphorylase and thus of glycogen degradation in astrocytes.
Dringen
R
R
Physiologisch Chemisches Institut der Universität, Tübingen, F.R.G.
Hamprecht
B
B
D019325:3-O-Methylglucose; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology*; D005942:Gluconates / Q000494:pharmacology*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D007783:Lactones; D008757:Methylglucosides / Q000494:pharmacology; D006005:Phosphorylases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D005942:Gluconates; D005958:Glucosephosphates; D007783:Lactones; D008757:Methylglucosides; D019325:3-O-Methylglucose; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D006003:Glycogen; D003847:Deoxyglucose; D006005:Phosphorylases; C010730:beta-glucono-1,5-lactone