Romani A, Dowell E, Scarpa A
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4901.
J Biol Chem. 1991 Dec 25;266(36):24376-84.
The addition of norepinephrine, epinephrine, or forskolin to collagenase-dispersed rat liver hepatocytes increase cAMP and result in a 15% loss in total cell Mg2+ within 5 min. Conversely, carbachol and vasopressin induce a 10-15% increase of total cell Mg2+. Permeabilized hepatocytes also mobilize a large pool of Mg2+ when stimulated by ADP or cAMP. This stimulation is completely inhibited by atractyloside and bongkrekic acid, two different specific inhibitors of the mitochondrial adenine nucleotide translocase. cAMP directly mobilizes Mg2+ efflux from isolated rat liver mitochondria. 50 nM cAMP or 250 microM ADP induces in 5 min a mitochondrial loss of about 6 nmol of Mg2+/mg of protein and a stimulation of ATP efflux. The effect of cAMP is specific, is not reproduced by other cyclic or noncyclic nucleotides, and is inhibited by inhibitors of the adenine nucleotide translocase. These data indicate that cAMP is a messenger for a major mobilization of Mg2+ in hepatocytes. A major target for the effect of cAMP are mitochondria, which lose up to 20-25% of their total Mg2+ in 5 min, both within the cell and after isolation. Evidence is presented suggesting that the adenine nucleotide translocase is the target of the cAMP-dependent Mg2+ efflux and that cAMP may change the operation of the translocase. This, in turn, could change within the matrix the substrate of choice of the translocase from ATP to ATP.Mg.
向用胶原酶分散的大鼠肝脏肝细胞中添加去甲肾上腺素、肾上腺素或福斯高林会增加细胞内的环磷酸腺苷（cAMP），并导致在5分钟内细胞内总镁离子（Mg2+）损失15%。相反，卡巴胆碱和血管加压素会使细胞内总镁离子增加10%-15%。经透化处理的肝细胞在受到二磷酸腺苷（ADP）或cAMP刺激时，也会释放大量的镁离子。这种刺激完全被两种不同的线粒体腺嘌呤核苷酸转位酶特异性抑制剂——苍术苷和邦克酸所抑制。cAMP可直接促使分离出的大鼠肝脏线粒体释放镁离子。50 nM的cAMP或250 microM的ADP在5分钟内会导致线粒体损失约6 nmol的Mg2+/mg蛋白质，并刺激三磷酸腺苷（ATP）外流。cAMP的作用具有特异性，其他环核苷酸或非环核苷酸无法产生同样的效果，且会被腺嘌呤核苷酸转位酶抑制剂所抑制。这些数据表明，cAMP是肝细胞中镁离子大量动员的信使。cAMP作用的一个主要靶点是线粒体，无论是在细胞内还是分离后，线粒体在5分钟内会损失其总镁离子的20%-25%。有证据表明，腺嘌呤核苷酸转位酶是cAMP依赖性镁离子外流的靶点，并且cAMP可能会改变转位酶的运作。这反过来可能会改变线粒体内转位酶的底物选择，从ATP变为ATP.Mg。
