Keppens S, Vandenheede J R, De Wulf H
Biochim Biophys Acta. 1977 Feb 28;496(2):448-57. doi: 10.1016/0304-4165(77)90327-0.
We have studied the mode of action of three hormones (angiotensin, vasopressin and phenylephrine, an alpha-adrenergic agent) which promote liver glycogenolysis in a cyclic AMP-independent way, in comparison with that of glucagon, which is known to act essentially via cyclic AMP. The following observations were made using isolated rat hepatocytes: (a) In the normal Krebs-Henseleit bicarbonate medium, the hormones activated glycogen phosphorylase (EC 2.4.1.1) to about the same degree. In contrast to glucagon, the cyclic AMP-independent hormones did not activate either protein kinase (EC 2.7.1.37) or phosphorylase b kinase (EC 2.7.1.38). (b) The absence of Ca2+ from the incubation medium prevented the activation of glycogen phosphorylase by the cyclic AMP-independent agents and slowed down that induced by glucagon. (c) The ionophore A 23187 produced the same degree of activation of glycogen phosphorylase, provided that Ca2+ was present in the incubation medium. (d) Glucagon, cyclic AMP and three cyclic AMP-dependent hormones caused an enhanced uptake of 45Ca; it was verified that concentrations of angiotensin and of vasopressin known to occur in haemorrhagic conditions were able to produce phosphorylase activation and stimulate 45Ca uptake. (e) Appropriate antagonists (i.e. phentolamine against phenylephrine and an angiotensin analogue against angiotensin) prevented both the enhanced 45Ca uptake and the phosphorylase activation. We interpret our data in favour of a role of calcium (1) as the second messenger in liver for the three cyclic AMP-independent glycogenolytic hormones and (2) as an additional messenger for glucagon which, via cyclic AMP, will make calcium available to the cytoplasm either from extracellular or from intracellular pools. The target enzyme for Ca2+ is most probably phosphorylase b kinase.
我们研究了三种以不依赖环磷酸腺苷（cAMP）的方式促进肝糖原分解的激素（血管紧张素、血管加压素和苯肾上腺素，一种α-肾上腺素能剂）的作用模式，并与已知主要通过环磷酸腺苷起作用的胰高血糖素进行了比较。使用分离的大鼠肝细胞进行了以下观察：（a）在正常的 Krebs-Henseleit 碳酸氢盐培养基中，这些激素激活糖原磷酸化酶（EC 2.4.1.1）的程度大致相同。与胰高血糖素不同，不依赖环磷酸腺苷的激素既不激活蛋白激酶（EC 2.7.1.37）也不激活磷酸化酶b激酶（EC 2.7.1.38）。（b）孵育培养基中缺乏钙离子会阻止不依赖环磷酸腺苷的试剂激活糖原磷酸化酶，并减缓胰高血糖素诱导的激活。（c）离子载体A 23187在孵育培养基中存在钙离子的情况下，产生相同程度的糖原磷酸化酶激活。（d）胰高血糖素、环磷酸腺苷和三种依赖环磷酸腺苷的激素导致45Ca摄取增加；已证实已知在出血情况下出现的血管紧张素和血管加压素浓度能够产生磷酸化酶激活并刺激45Ca摄取。（e）适当的拮抗剂（即针对苯肾上腺素的酚妥拉明和针对血管紧张素的血管紧张素类似物）可阻止45Ca摄取增加和磷酸化酶激活。我们对数据的解释支持钙的作用：（1）作为肝脏中三种不依赖环磷酸腺苷的糖原分解激素的第二信使；（2）作为胰高血糖素的额外信使，胰高血糖素通过环磷酸腺苷将钙从细胞外或细胞内储存库释放到细胞质中。钙离子的靶酶很可能是磷酸化酶b激酶。
