Regulation of hepatic glycogen phosphorylase and glycogen synthase by calcium and diacylglycerol.
Incubation of rat hepatocytes with angiotensin II (1 nM) produced a time-dependent accumulation of 1, 2-diacylglycerol and inactivation of glycogen synthase with maximum effects at 10 min. The level of diacylglycerol then gradually declined and the activity of glycogen synthase I returned to control values at 30 min. In contrast, angiotensin II caused an increase in cytosolic Ca2+ and an activation of glycogen phosphorylase which were rapid and transient, reaching maximum values in less than 2 min and then returning to control levels at 15 min. There were excellent correlations between the changes in glycogen synthase I and diacylglycerol levels and between the changes in phosphorylase alpha and cytosolic Ca2+ in these time-course studies. However, there was no correlation between the changes in diacylglycerol and phosphorylase alpha or between the changes in cytosolic Ca2+ and glycogen synthase I. Norepinephrine also caused a slow increase in diacylglycerol and inactivation of glycogen synthase, and a rapid increase in cytosolic free Ca2+ and activation of glycogen phosphorylase. Addition of an alpha1-adrenergic blocker (prazosin or phentolamine) caused rapid decreases in cytosolic free Ca2+ and phosphorylase alpha, but only slowly reversed the inactivation of synthase and accumulation of diacylglycerol. The dose-response curves for norepinephrine and prazosin on glycogen synthase were well correlated with those on diacylglycerol. It is proposed that in liver cells, Ca2+-mobilizing hormones regulate phosphorylase a through a Ca2+-dependent mechanism and inactivate glycogen synthase through the generation of diacylglycerol, at least in part. The data provide additional support for the view that protein kinase C may be important in the regulation of glycogen synthase in liver.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004075:Diglycerides / Q000502:physiology*; D005989:Glycerides / Q000502:physiology*; D006006:Glycogen Synthase / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats
D004075:Diglycerides; D005989:Glycerides; D000804:Angiotensin II; D006005:Phosphorylases; D006006:Glycogen Synthase; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine