Poggioli J, Mauger J P, Claret M
Biochem J. 1986 May 1;235(3):663-9. doi: 10.1042/bj2350663.
The effect of the interaction between the Ca2+-mobilizing hormone adrenaline, used as alpha-adrenergic agonist, and cyclic AMP-dependent hormones, including beta-adrenergic agonists and glucagon, on the initial 45Ca2+ uptake rate and polyphosphoinositide metabolism were investigated in isolated rat hepatocytes. Each hormone alone increased the initial 45Ca2+ uptake rate. When adrenaline was added without inhibitor, it induced a rise in the initial 45Ca2+ uptake rate larger than the sum of the rises elicited by its alpha and beta components singly. Similarly, when adrenaline was used as an alpha-agonist and added together with glucagon, it enhanced the initial 45Ca2+ uptake rate synergistically. Kinetic analysis of the initial 45Ca2+ uptake rate measured at different Ca2+ concentrations suggested that the increased influx elicited by the combination of adrenaline as alpha-adrenergic agonist and glucagon reflects an activation of the rate of Ca2+ transport via a homogeneous population of Ca2+ channels or carriers. Dose-response curves for the alpha-adrenergic action of adrenaline or glucagon applied in the presence of increasing doses of glucagon or adrenaline showed that each hormone increases the maximal response to the other without affecting its ED50. Measurement of polyphosphoinositide hydrolysis and of the inositol phosphates formed in the presence of adrenaline or vasopressin and/or glucagon showed that Ca2+-mobilizing hormones and glucagon had no synergistic effects on inositol 1,4,5-trisphosphate production. It is therefore proposed that the synergistic action of glucagon and Ca2+-mobilizing hormones on Ca2+ influx occurs at a step that takes place close to the Ca2+ channels or carriers themselves. The Ca2+ gating involved might be mainly controlled by two products, one of them arising from the polyphosphoinositide metabolism, and the other from the increase in internal cyclic AMP.
以α - 肾上腺素能激动剂使用的钙离子动员激素肾上腺素与包括β - 肾上腺素能激动剂和胰高血糖素在内的环磷酸腺苷依赖性激素之间的相互作用,对分离的大鼠肝细胞中初始45Ca2 +摄取率和多磷酸肌醇代谢的影响进行了研究。单独使用每种激素均可提高初始45Ca2 +摄取率。当不加抑制剂添加肾上腺素时,它诱导的初始45Ca2 +摄取率升高大于其α和β成分单独引起的升高之和。同样,当肾上腺素用作α - 激动剂并与胰高血糖素一起添加时,它协同增强了初始45Ca2 +摄取率。在不同Ca2 +浓度下测量初始45Ca2 +摄取率的动力学分析表明,作为α - 肾上腺素能激动剂的肾上腺素和胰高血糖素组合引起的流入增加反映了通过均匀的Ca2 +通道或载体群体的Ca2 +转运速率的激活。在增加剂量的胰高血糖素或肾上腺素存在下应用的肾上腺素或胰高血糖素的α - 肾上腺素能作用的剂量 - 反应曲线表明,每种激素增加了对另一种激素的最大反应,而不影响其ED50。在肾上腺素或血管加压素和/或胰高血糖素存在下对多磷酸肌醇水解和形成的肌醇磷酸的测量表明,钙离子动员激素和胰高血糖素对肌醇1,4,5 - 三磷酸的产生没有协同作用。因此,有人提出胰高血糖素和钙离子动员激素对Ca2 +流入的协同作用发生在靠近Ca2 +通道或载体本身的步骤。所涉及的Ca2 +门控可能主要由两种产物控制,其中一种来自多磷酸肌醇代谢,另一种来自细胞内环磷酸腺苷的增加。