ION GRADIENTS AND METABOLIC ENERGY IN ANIMAL TISSUE

工作灌注心脏中九种主要无机离子的梯度能量彼此接近平衡，胞外和胞内相之间的电势和ATP水解的DG接近平衡（增田T等，J Biol Chem 1990;265：20321-34）。乙醇的代谢使肝细胞的静息电位从28 mV增加到40 mV（Veech RL等人，Alcoholism Clin Expt Stud 1994;18：1040-56）。我们完成了乙醇诱导的肝电压变化对门静脉血和肝脏之间的所有氨基酸的梯度和9种主要无机离子的梯度之间的细胞内和细胞外空间在大鼠肝脏在体内的影响的研究。据我们所知，这是第一次这样的研究。 我们的工作也是第一个表明肝脏乙醇代谢的终产物乙酸盐完全阻断肠道对l-谷氨酰胺的摄取。谷氨酰胺不仅被认为是蛋白质的基本组成部分，而且被认为是细菌屏障。醋酸盐抑制肠道利用l-谷氨酰胺的能力的含义仍有待确定。 先前，我们表明，仅仅改变可用的底物就改变了心脏中ATP水解的DG（Kashiwaya Y等人，Am J Cardiol 1997;80：50 A-64 A）。由于任何类型的损伤都会诱导细胞离子分布的定型变化，其中细胞获得Na+，失去K+并肿胀，因此这些损伤的定型变化可能通过简单地改变给予损伤或烧伤受害者的液体组成而逆转。由于这些研究和我们向医学院召集的专家组提出的建议，已经提出了一项建议，即开始研究制造新的复苏液体的可行性（见：液体复苏，治疗战斗伤亡和平民受伤的科学现状，国家学院出版社，1999年）。目标是改善出血和烧伤的标准治疗，这在过去50年中没有改变。我们正在这方面进行合作。

The energy of the gradients of the nine major inorganic ions in working perfused heart are in near equilibrium with each other, the electrical potential between extra- and intracellular phase and the DG of ATP hydrolysis (Masuda T et al, J Biol Chem 1990;265:20321-34). The metabolism of ethanol increases the resting electrical potential of hepatocytes from 28 to 40 mV (Veech RL et al, Alcoholism Clin Expt Stud 1994;18:1040-56). We have completed a study of the effects of ethanol-induced change in hepatic voltage upon the gradients of all the amino acids between portal vein blood and liver and the gradients of the 9 major inorganic ions between intracellular and extracellular space in rat liver in vivo. To our knowledge, this is the first such study. Our work is also the first to show that the end product of hepatic ethanol metabolism, acetate, completely blocks the gut uptake of l-glutamine. l-Glutamine had been thought to be essential not only for its function as a building block for proteins, but also for its action as a bacterial barrier. The implication of the ability of acetate to inhibit the gut utilization of l-glutamine remains to be determined. Previously, we showed that merely changing the substrate available altered the DG of ATP hydrolysis in heart (Kashiwaya Y et al, Am J Cardiol 1997;80:50A-64A). Since injuries of any sort induce a stereotypic change in cellular ionic distributions wherein the cell gains Na+, loses K+ and swells, these stereotypic changes of injury can possibly be reversed by simple changes in the compositions of fluids administered to victims of injury or burns. As a result of these studies and our suggestions to a panel convened by the Academy of Medicine, a recommendation has been made that investigation of the feasibility of making new resuscitation fluids be initiated (see: Fluid Resuscitation, state of the science for treating combat casualties and civilian injuries, National Academy Press, 1999). The goal is to improve the standard treatment of hemorrhage and burns, which has not changed over the past 50 years. We are collaborating in this effort.