Exton J H, Assimacopoulos-Jeannet F D, Blackmore P F, Cherrington A D, Chan T M
Adv Cyclic Nucleotide Res. 1978;9:441-52.
Epinephrine rapidly activates phosphorylase in hepatocytes, mainly by a mechanism(s) involving alpha-adrenergic and not beta-adrenergic receptors. The alpha-adrenergic mechanism does not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. It is impaired when hepatocytes are depleted of calcium by EGTA treatment and is rapidly restored by readdition of calcium. Basal phosphorylase is also lowered by calcium deficiency and rapidly increased by calcium but not other divalent cations. The divalent cation ioniphore A23187 increases phosphorylase a levels in hepatocytes in a calcium-dependent manner. Calcium deficiency does not modify the effects of glucagon, cAMP, or beta-adrenergic activation on phosphorylase. Activation of alpha-adrenergic receptors rapidly increases 45Ca fluxes in hepatocytes. Glucagon produces similar effects, but supraphysiological concentrations are required. The hypothesis is advanced that alpha-adrenergic activation of phosphorylase involves alterations in cell calcium such that there is an increase in cytosolic Ca2+ concentration leading to increased phosphorylase kinase activity. Epinephrine induces greater cAMP accumulation in calcium-depleted cells than in normal cells. The effect is mediated by alpha-adrenergic and not beta-adrenergic receptors. Calcium deficiency also cuases cAMP accumulation in hepatocytes incubated with phenylephrine but does not modify the responses of the cells to isoproterenol, glucagon, or cAMP. Low concentrations of calcium rapidly reverse alpha-adrenergic receptor-mediated cAMP accumulation in calcium-depleted cells. The hypothesis is advanced that calcium normally exerts an inhibitory effect on a linkage between alpha-adrenergic receptors and adenylate cyclase in hepatocytes.
肾上腺素主要通过涉及α - 肾上腺素能而非β - 肾上腺素能受体的机制快速激活肝细胞中的磷酸化酶。α - 肾上腺素能机制不涉及环磷酸腺苷（cAMP）的积累或cAMP依赖性蛋白激酶的激活。当用乙二醇双四乙酸（EGTA）处理使肝细胞缺钙时，该机制受损，而再添加钙后可迅速恢复。基础磷酸化酶也会因缺钙而降低，并因钙而非其他二价阳离子而迅速增加。二价阳离子载体A23187以钙依赖的方式增加肝细胞中磷酸化酶a的水平。缺钙不会改变胰高血糖素、cAMP或β - 肾上腺素能激活对磷酸化酶的影响。α - 肾上腺素能受体的激活会迅速增加肝细胞中的45Ca通量。胰高血糖素产生类似的效果，但需要超生理浓度。有人提出假说，即磷酸化酶的α - 肾上腺素能激活涉及细胞钙的改变，使得胞质Ca2 +浓度增加，导致磷酸化酶激酶活性增强。肾上腺素在缺钙细胞中诱导的cAMP积累比在正常细胞中更多。这种作用是由α - 肾上腺素能受体而非β - 肾上腺素能受体介导的。缺钙也会导致用去氧肾上腺素孵育的肝细胞中cAMP积累，但不会改变细胞对异丙肾上腺素、胰高血糖素或cAMP的反应。低浓度的钙能迅速逆转缺钙细胞中α - 肾上腺素能受体介导的cAMP积累。有人提出假说，即钙通常对肝细胞中α - 肾上腺素能受体与腺苷酸环化酶之间的联系发挥抑制作用。
