Taylor W M, Prpić V, Exton J H, Bygrave F L
Biochem J. 1980 May 15;188(2):443-50. doi: 10.1042/bj1880443.
Mitochondria isolated from rat liver after a short-term perfusion with the alpha-adrenergic agonist phenylephrine or with glucagon exhibited enhanced rates of uptake of Ca2+ and prolonged retention of Ca2+ in the presence of 4mm-P(i). The effect of Ca2+ retention was apparent after perfusion with phenylephrine for only 1min and was maximal after 7min of treatment. The changes induced by glucagon, although similar, were less rapid. Adrenaline caused similar changes to phenylephrine and its effects were blocked by the alpha-adrenergic antagonist phenoxybenzamine, but not by the beta-antagonist propranolol. The Ca2+ content of the isolated mitochondria decreased by 30% 1min after the onset of perfusion with phenylephrine; by 6min it had begun to return to the original value which was reached at 10min. A similar loss in calcium content was induced by glucagon but the changes were not as great and occurred more slowly. Mitochondria from phenylephrine-treated livers exhibited decreased rates of Ca2+ efflux induced by addition of 2mm-EGTA, a 50% increase in the contents of ADP and total adenine nucleotides, a small increase in the transmembrane pH gradient, and a reduced rate of oxaloacetate-induced NADPH oxidation. This study thus shows that stimulation of liver by alpha-adrenergic agonists, like that by glucagon, induces within minutes a stable modification of mitochondria leading to alterations in the Ca2+-translocation cycle (increased Ca2+ uptake and retention) and alterations in mitochondrial energy-linked reactions.
用α-肾上腺素能激动剂去氧肾上腺素或胰高血糖素对大鼠肝脏进行短期灌注后分离得到的线粒体，在存在4mM无机磷酸盐（P(i)）的情况下，表现出Ca2+摄取速率增强以及Ca2+保留时间延长。在用去氧肾上腺素灌注仅1分钟后，Ca2+保留的效果就很明显，在处理7分钟后达到最大值。胰高血糖素引起的变化虽然相似，但速度较慢。肾上腺素引起的变化与去氧肾上腺素相似，其作用被α-肾上腺素能拮抗剂酚苄明阻断，但不被β-拮抗剂普萘洛尔阻断。在用去氧肾上腺素灌注开始1分钟后，分离的线粒体中的Ca2+含量下降了30%；到6分钟时，它开始恢复到10分钟时达到的原始值。胰高血糖素也诱导了类似的钙含量损失，但变化没有那么大，而且发生得更慢。来自用去氧肾上腺素处理过的肝脏的线粒体，在添加2mM乙二醇双（2-氨基乙基醚）四乙酸（EGTA）后，Ca2+外流速率降低，二磷酸腺苷（ADP）和总腺嘌呤核苷酸含量增加50%，跨膜pH梯度略有增加，草酰乙酸诱导的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化速率降低。因此，这项研究表明，α-肾上腺素能激动剂对肝脏的刺激，与胰高血糖素一样，在几分钟内就会诱导线粒体的稳定改变，导致Ca2+转运循环的改变（Ca2+摄取和保留增加）以及线粒体能量相关反应的改变。
