The Role of Calcium in Alpha-adrenergic Inactivation of Glycogen Synthase in Rat Hepatocytes and its Inhibition by Insulin
The Role of Calcium in Alpha-adrenergic Inactivation of Glycogen Synthase in Rat Hepatocytes and its Inhibition by Insulin
复制标题
钙在大鼠肝细胞糖原合成酶α-肾上腺素能失活中的作用及其胰岛素抑制作用
作者：
G. W. Strickland;P. Blackmore;J. Exton
研究了肾上腺素、加压素和A23187对饲养动物分离的大鼠肝实质细胞糖原合成酶和磷酸化酶的影响。在正常的含钙肝细胞中，肾上腺素、加压素和A23187对先前用30 mM葡萄糖激活的糖原合成酶的失活作用比对磷酸化酶的激活作用更强。在缺钙肝细胞(用1 mM EGTA清洗和孵育的细胞)中，肾上腺素对这两种酶活性的影响受到损害，而加压素和A23187的作用则完全消失。胰岛素能更有效地抑制肾上腺素对钙耗竭细胞的作用，但对加压素和A23187的作用没有影响。肾上腺素、加压素和A23187诱导细胞钙外流的能力不会因30 mM葡萄糖的存在而改变。这些发现与肝糖原合成酶的α肾上腺素能失活可能是钙依赖的蛋白激酶，可能是磷酸化b激酶刺激增加的结果是一致的。
SUMMARY The effects of epinephrine, vasopressin, and A23187 on glycogen synthase and phosphorylase were examined in isolated rat liver parenchymal cells from fed animals. In normal calcium-containing hepatocytes, epinephrine, vasopressin, and A23187 were more potent at inactivating glycogen synthase, previously activated with 30 mM glucose, than at activating phosphorylase. In calcium-depleted hepatocytes (cells washed and incubated with 1 mM EGTA), the effect of epinephrine on both enzyme activities was impaired, while the effects of vasopressin and A23187 were completely abolished. Insulin was more effective at inhibiting the effects of epinephrine in calcium-depleted cells, but it was without effect on vasopressin and A23187 actions. The ability of epinephrine, vasopressin, and A23187 to elicit calcium efflux from cells was not altered by the presence of 30 mM glucose. These findings are consistent with the idea that the α-adrenergic inactivation of liver glycogen synthase may be a result of the increased stimulation of a calcium-dependent protein kinase, possibly phosphorylase b kinase.