ANION TRANSPORT IN EHRLICH CARCINOMA CELLS

我们研究的总体目标是描述 艾氏小鼠腹水的无机阴离子通透途径 癌细胞。氯化物、硫酸盐和硫酸盐的动力学特征 无机磷通过质膜的运输表明，在 命令这些阴离子进入它们必须首先与之相互作用的细胞 特定的膜载体系统。以前的研究已经提供了证据 与氯化物和硫酸盐利用单一载体的观点一致 具有两个反应点的体系，而磷酸盐完全利用 独立的系统。最近的研究表明，氯化物利用了三种 不同的渗透途径：非中介扩散(10%)、共运输 与钾和钠(40%)结合，并通过 阴离子转运蛋白(50%)。在过去的一年里，我们调查了 共运输途径的一些细节。我们的结果表明，为了 通过这种机制运输的氯化物钾和钠都是 必填项。 在稳态(生理)条件下的细胞中，阴离子/阳离子 37℃时的化学计量比为：2Cl：1Na：1K。氯离子的转运由 阴离子交换剂(氯自交换)在高电压下表现出自抑制作用 胞外氯，当pho降至5.5时被废除。这 研究结果表明，H+在细胞表面的修饰(抑制)部位相互作用。 阴离子转运体，这样做可以解除抑制。与之形成鲜明对比的是 氯化物，大约85%的磷酸盐运输依赖于 胞外培养液中的钠。我们已经证明了单价 磷酸盐是主要的，如果不是唯一的，运输和 细胞内pH的降低会导致转运受阻。在……里面 在这个项目的下一年，我们计划进一步描述阳离子 氯离子-阳离子共转运途径的要求。我们是 特别感兴趣的是这种运输系统 在生理稳定期间从双向交换切换 当肿瘤细胞处于(恒定细胞体积)状态时，以净转运途径 音量是可以调节的。(A)

The overall objective of our research is the characterization of the inorganic anion permeability pathways of the Ehrlich mouse ascites carcinoma cell. The kinetic characteristics of chloride, sulfate, and inorganic phosphate transport across the plasma membrane suggest that in order for these anions to enter the cell they must first interact with specific membrane carrier systems. Previous studies have provided evidence consistent with the view that chloride and sulfate utilize a single carrier system possessing two reactive sites, while phosphate utilizes an entirely separate system. Recent studies have shown that chloride utilizes three separate permeability pathways: nonmediated diffusion (10%), co-transport with potassium and sodium (40%), and mediated self-exchange through the anion transporter (50%). During the past year, we have investigated the co-transport pathway in some detail. Our results show that in order for chloride to be transported by this mechanism both potassium and sodium are required. In cells under steady state (physiological) conditions, the anion/cation stoichiometry at 37~C is: 2Cl:1Na:1K. Chloride transport mediated by the anion exchanger (Cl self-exchange) exhibits self-inhibition at high extracellular chloride which is abolished when pHo is lowered to 5.5. This finding suggests that H+ interacts at a modifier (inhibitory) site on the anion transporter and in so doing relieves inhibition. In contrast to chloride, about 85% of phosphate transport depends on the presence of sodium in the extracellular medium. We have shown that monovalent phosphate is the predominate, if not exclusive, species transported and that a decrease in intracellular pH results in inhibition of transport. In the next year of this project, we plan to further characterize the cation requirements of the chloride-cation co-transport pathway. We are particularly interested in the mechanism by which this transport system switches from a bi-directional exchange during the physiological steady state (constant cell volume) to a net transport pathway when the tumor cell volume regulates. (A)