Hormonal regulation of hepatic glycogen synthase phosphatase.
Perfusion of livers from fed rats with medium containing glucagon (2 x 10(-10) or 1 x 10(-8) M) resulted in both time- and concentration-dependent inactivation of glycogen synthase phosphatase. Expected changes occurred in cAMP, cAMP-dependent protein kinase, glycogen synthase, and glycogen phosphorylase. The effect of glucagon on synthase phosphatase was partially reversed by simultaneous addition of insulin (4 x 10(-8) M), an effect paralleled by a decrease in cAMP. Addition of arginine vasopressin (10 milliunits/ml) resulted in a similar inactivation of synthase phosphatase and activation of phosphorylase, but independent of any changes in cAMP or its kinase. Phosphorylase phosphatase activity was unaffected by any of these hormones. Synthase phosphatase activity, measured as the ability of a crude homogenate to catalyze the conversion of purified rat liver synthase D to the I form, was no longer inhibited by glucagon or vasopressin when phosphorylase antiserum was added to the phosphatase assay mixture in sufficient quantity to inhibit 90-95% of the phosphorylase a activity. These data support the following conclusions: 1) hepatic glycogen synthase phosphatase activity is acutely modulated by hormones, 2) hepatic glycogen synthase phosphatase and phosphorylase phosphatase are regulated differently, 3) the hormone-mediated changes in synthase phosphatase cannot be explained by an alteration of the synthase D molecule affecting its behavior as a substrate, and 4) glycogen synthase phosphatase activity is at least partially controlled by the level of phosphorylase a.
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000378:metabolism; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010477:Perfusion; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats
D007328:Insulin; D001127:Arginine Vasopressin; D005934:Glucagon; D000242:Cyclic AMP; D010762:Phosphorylase a; D006006:Glycogen Synthase; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D006007:Glycogen-Synthase-D Phosphatase