Evidence for alpha adrenergic activation of phosphorylase and inactivation of glycogen synthase in rat adipocytes. Effects of alpha and beta adrenergic agonists and antagonists on glycogen synthase and phosphorylase.
Evidence for alpha adrenergic activation of phosphorylase and inactivation of glycogen synthase in rat adipocytes. Effects of alpha and beta adrenergic agonists and antagonists on glycogen synthase and phosphorylase.
复制标题
大鼠脂肪细胞中磷酸化酶的α肾上腺素能激活和糖原合酶失活的证据。
作者：
J. Lawrence;J. Larner,
本文观察了α、β肾上腺素能激动剂和拮抗剂对大鼠脂肪细胞磷酸化酶a百分率和糖原合成酶I活性的影响。(-)-肾上腺素、(-)-去甲肾上腺素和(-)-异丙肾上腺素可剂量依赖性地增加环磷酸腺苷(CAMP)浓度和磷酸化酶a活性百分比。与肾上腺素或去甲肾上腺素相比，异丙肾上腺素在增加糖原合成酶I活性和降低糖原合成酶I活性方面的效力约为肾上腺素或去甲肾上腺素的10倍。虽然这三种药物对合成酶I活性的抑制程度相同，但肾上腺素和去甲肾上腺素对磷酸化酶a活性的最大影响比异丙肾上腺素的最大作用大约25%。在α肾上腺素能拮抗剂酚妥拉明、苯氧苯甲胺和二氢麦角胺存在下，去甲肾上腺素增加磷酸化酶a百分率的最大作用减弱为异丙肾上腺素。三种α-肾上腺素能拮抗剂均增强去甲肾上腺素增加cAMP浓度的能力。(-)-苯肾上腺素对磷酸化酶a活性的最大影响小于异丙肾上腺素的最大作用。当细胞与异丙肾上腺素和苯肾上腺素孵育时，磷酸化酶a的活性增加到与肾上腺素或去甲肾上腺素观察到的水平。甲氧胺也提高了磷酸化酶a的活性，异丙肾上腺素和甲氧胺对磷酸化酶的影响是相加的。细胞与5 mM二丁酰cAMP孵育后，合酶I活性降低，磷酸化酶a活性升高，达到异丙肾上腺素的水平。当二丁酰cAMP与异丙肾上腺素或肾上腺素一起加入到细胞中时，没有观察到比单独用儿茶酚胺获得的磷酸化酶a活性进一步增加。然而，当细胞与苯肾上腺素和二丁酰cAMP孵育时，磷酸化酶a活性的百分比增加到肾上腺素所观察到的百分比。(-)-普萘洛尔完全阻断肾上腺素、去甲肾上腺素或去甲肾上腺素孵育细胞后cAMP的升高；但仍可观察到磷酸化酶a活性的增加和合成酶I活性的降低。用20微克心得安和1微克苯氧基苯甲胺共同孵育细胞，不能逆转200毫单位/毫升促肾上腺皮质激素引起的合酶I活性下降，但完全取消200微克苯肾上腺素的作用。细胞与甲氧胺(1-10微米)孵育可降低糖原合成酶I的活性。酚妥拉明(20微米)完全阻断甲氧胺的这一作用，以及甲氧胺增加磷酸化酶a活性的能力。
The effects of alpha and beta adrenergic agonists and antagonists on the percentages of phosphorylase a and glycogen synthase I activities were investigated in isolated rat adipocytes. (-)-Epinephrine, (-)-norepinephrine, and (-)-isoproterenol increased the concentration of adenosine cyclic 39,59-monophosphate (cAMP) and the percentage of phosphorylase a activity in a dose-dependent manner. Isoproterenol was about 10 times more potent than epinephrine or norepinephrine with respect to these increases as well as to decreases in the percentage of glycogen synthase I activity. Although all three agents decreased synthase I activity to the same extent, the maximal effects of epinephrine and norepinephrine on phosphorylase a activity were approximately 25% greater than the maximal effect of isoproterenol. In the presence of the alpha adrenergic antagonists phentolamine, phenoxybenzamine, and dihydroergotamine, the maximal effect of norepinephrine on increasing the percentage of phosphorylase a was reduced to that of isoproterenol. All three alpha adrenergic antagonists potentiated the ability of norepinephrine to increase the concentration of cAMP. The maximal effect of (-)-phenylephrine on phosphorylase a activity was less than the maximal effect of isoproterenol. When cells were incubated with isoproterenol plus phenylephrine, phosphorylase a activity was increased to levels observed with epinephrine or norepinephrine. Methoxamine also increased phosphorylase a activity, and the effects of isoproterenol and methoxamine on phosphorylase were additive. Incubation of cells with 5 mM dibutyryl cAMP decreased synthase I activity and increased phosphorylase a activity to the level observed with isoproterenol. When dibutyryl cAMP was added to cells together with isoproterenol or epinephrine, no further increase in phosphorylase a activity over that obtained with the catecholamines alone was observed. However, when cells were incubated with phenylephrine plus dibutyryl cAMP, the percentage of phosphorylase a activity was increased to that observed with epinephrine. (-)-Propranolol completely blocked the rise in cAMP observed following incubation of cells with epinephrine, norepinephrine, or phenylephrine; yet an increase in phosphorylase a activity and a decrease in synthase I activity were still observed. Incubation of cells with 20 µM propranolol together with 1 µM phenoxybenzamine did not reverse the decrease in synthase I activity produced by 200 milliunits/ml of adrenocorticotrophic hormone, but completely abolished the effect of 200 µM phenylephrine. Incubation of cells with methoxamine (1-10 µM) decreased glycogen synthase I activity. Phentolamine (20 µM) completely blocked this effect of methoxamine, as well as the ability of methoxamine to increase phosphorylase a activity.