Altin J G, Bygrave F L
Biochem J. 1986 Sep 15;238(3):653-61. doi: 10.1042/bj2380653.
A perfused liver system incorporating a Ca2+-sensitive electrode was used to study the long-term effects of glucagon and cyclic AMP on the mobilization of Ca2+ induced by phenylephrine, vasopressin and angiotensin. At 1.3 mM extracellular Ca2+ the co-administration of glucagon (10 nM) or cyclic AMP (0.2 mM) and a Ca2+-mobilizing hormone led to a synergistic potentiation of Ca2+ uptake by the liver, to a degree which was dependent on the order of hormone administration. A maximum net amount of Ca2+ influx, corresponding to approx. 3800 nmol/g of liver (the maximum rate of influx was 400 nmol/min per g of liver), was induced when cyclic AMP or glucagon was administered about 4 min before vasopressin and angiotensin. These changes are over an order of magnitude greater than those induced by Ca2+-mobilizing hormones alone [Altin & Bygrave (1985) Biochem. J. 232, 911-917]. For a maximal response the influx of Ca2+ was transient and was essentially complete after about 20 min. Removal of the hormones was followed by a gradual efflux of Ca2+ from the liver over a period of 30-50 min; thereafter, a similar response could be obtained by a second administration of hormones. Dose-response measurements indicate that the potentiation of Ca2+ influx by glucagon occurs even at low (physiological) concentrations of the hormone. By comparison with phenylephrine, the stimulation of Ca2+ influx by vasopressin and angiotensin is more sensitive to low concentrations of glucagon and cyclic AMP, and can be correlated with a 20-50-fold increase in the calcium content of mitochondria. The reversible uptake of such large quantities of Ca2+ implicates the mitochondria in long-term cellular Ca2+ regulation.
利用一个包含钙离子敏感电极的灌注肝脏系统，研究胰高血糖素和环磷酸腺苷（cAMP）对去氧肾上腺素、血管加压素和血管紧张素诱导的钙离子动员的长期影响。在细胞外钙离子浓度为1.3 mM时，同时给予胰高血糖素（10 nM）或环磷酸腺苷（0.2 mM）与一种钙离子动员激素，会导致肝脏对钙离子摄取的协同增强，增强程度取决于激素给药顺序。当在血管加压素和血管紧张素给药前约4分钟给予环磷酸腺苷或胰高血糖素时，会诱导出最大净钙离子内流，相当于约3800 nmol/g肝脏（最大内流速率为400 nmol/min per g肝脏）。这些变化比单独由钙离子动员激素诱导的变化大一个数量级以上[阿尔廷和拜格雷夫（1985年）《生物化学杂志》232卷，911 - 917页]。为了获得最大反应，钙离子内流是短暂的，在约20分钟后基本完成。去除激素后，钙离子在30 - 50分钟内从肝脏逐渐外流；此后，再次给予激素可获得类似反应。剂量反应测量表明，即使在低（生理）浓度的激素下，胰高血糖素也能增强钙离子内流。与去氧肾上腺素相比，血管加压素和血管紧张素对钙离子内流的刺激对低浓度的胰高血糖素和环磷酸腺苷更敏感，并且与线粒体钙含量增加20 - 50倍相关。如此大量钙离子的可逆摄取表明线粒体参与了细胞内钙离子的长期调节。
