Geisbuhler T P, Schwager T L
Department of Physiology, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501, USA.
J Mol Cell Cardiol. 1996 Sep;28(9):1857-66. doi: 10.1006/jmcc.1996.0178.
The loss of 5'-nucleotides (especially ATP and GTP) from cardiac muscle cells is a distinguishing feature of myocardial ischemia. Isolated adult rat cardiac myocytes were used as a model system to determine whether GTP depletion could affect (1) the ability of the myocytes to synthesize cyclic GMP (cGMP), or (2) the ability of the myocytes to respond to alpha-adrenergic challenge. Myocytes were made anoxic for 30- or 60-min periods, then challenged with either 1 mM sodium nitroprusside (NaNP) for 1 min or 40 microM norepinephrine (NE) for 20 min. The cells were extracted and the extracts assayed for cyclic GMP (NaNP challenge) or phosphoinositides (NE challenge). When challenged with NaNP, anoxic myocytes made up to five-fold more cGMP than aerobic controls (1401 +/- 353 fmol cGMP/mg cell protein in anoxic cells v 121 +/- 23 fmol/mg in aerobic controls). Phosphoinositide turnover was reduced in anoxic cells v aerobic controls. Stimulation of this pathway by NE was reduced two-fold after 30 min of anoxia, and abolished after 60 min of anoxia. Similar results were obtained with 30 microM and 60 microM phenylephrine. The authors concluded that nucleotide depletion under anoxic conditions has no effect on the production of cyclic GMP, but may interfere with the linkage of alpha-adrenergic receptors to phosphatidylinositol breakdown.
心肌细胞中5'-核苷酸（尤其是三磷酸腺苷和三磷酸鸟苷）的丢失是心肌缺血的一个显著特征。分离的成年大鼠心肌细胞被用作模型系统，以确定三磷酸鸟苷耗竭是否会影响：（1）心肌细胞合成环磷酸鸟苷（cGMP）的能力；或（2）心肌细胞对α-肾上腺素能刺激的反应能力。将心肌细胞缺氧处理30或60分钟，然后用1 mM硝普钠（NaNP）刺激1分钟或用40 μM去甲肾上腺素（NE）刺激20分钟。提取细胞并检测提取物中的环磷酸鸟苷（NaNP刺激）或磷酸肌醇（NE刺激）。当用NaNP刺激时，缺氧心肌细胞产生的环磷酸鸟苷比有氧对照多五倍（缺氧细胞中为1401±353 fmol环磷酸鸟苷/毫克细胞蛋白，而有氧对照中为121±23 fmol/毫克）。与有氧对照相比，缺氧细胞中的磷酸肌醇周转率降低。缺氧30分钟后，去甲肾上腺素对该途径的刺激作用降低了两倍，缺氧60分钟后则完全消失。用30 μM和60 μM苯肾上腺素也得到了类似的结果。作者得出结论，缺氧条件下的核苷酸耗竭对环磷酸鸟苷的产生没有影响，但可能会干扰α-肾上腺素能受体与磷脂酰肌醇分解的联系。
