ANION TRANSPORT IN EHRLICH CARCINOMA CELLS

埃利希癌细胞中的阴离子转运

• 批准号: 3170800
• 负责人: CHARLES LEVINSON
• 金额: $ 6.96万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170800
• 关键词: Ehrlich's tumor; acidity /alkalinity; adenosine triphosphate; anions; calcium metabolism; cell membrane; cell morphology; chemical hydration; chloride channels; furosemide; hypernatremia; hyponatremia; ion transport; ionophores; laboratory mouse; membrane permeability; membrane potentials; microelectrodes; neoplastic cell; osmosis; phosphates; potassium channel; sodium channel; sodium potassium exchanging ATPase; stoichiometry

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)

我们研究的总体目标是表征 埃利希小鼠腹水无机阴离子渗透途径 癌细胞 研究了氯化物、硫酸盐和 无机磷酸盐的跨膜转运表明， 为了使这些阴离子进入细胞，它们必须首先与 特定的膜载体系统。以前的实证研究显示 与氯化物和硫酸盐利用单一载体的观点一致 系统具有两个反应位点，而磷酸盐利用完全 分离系统。 最近的研究表明，氯化物利用三个 单独的渗透性途径：非介导扩散（10%），共转运 与钾和钠（40%），并通过介导的自我交换 阴离子转运蛋白（50%）。 在过去的一年里，我们调查了 共转运途径的一些细节。 我们的研究结果表明，为了 通过这种机制，钾和钠都可以被运输。 必需的. 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：1 Na：1 K。 介导的氯离子转运 阴离子交换剂（Cl自交换）在高温下表现出自抑制作用， 细胞外氯化物，当pHo降低到5.5时被消除。 这 研究表明，H+ 在修饰剂（抑制）位点上相互作用， 阴离子转运体，并在这样做解除抑制。 相比 在氯化物中，约85%的磷酸盐转运依赖于氯化物的存在。 细胞外介质中的钠。 我们已经证明，单价 磷酸盐是主要的，如果不是唯一的，物种运输， 细胞内pH的降低导致转运的抑制。 在 在这个项目的下一年，我们计划进一步表征阳离子， 氯化物-阳离子共运输途径的要求。 我们 特别感兴趣的是这个运输系统 在生理稳定期间从双向交换切换 当肿瘤细胞处于一个恒定的细胞体积状态时， 音量调节。 （一）