ROLE OF ALTERED MEMBRANE FUNCTION IN XENOBIOTIC TOXICITY

膜功能改变在异生物毒性中的作用

• 批准号: 4693292
• 负责人: J B PRITCHARD
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4693292
• 关键词: acidity /alkalinity; active transport; aminoacid transport; apical membrane; basolateral membrane; environmental toxicology; epithelium; hemolymph; ionophores; membrane permeability; membrane structure; nonelectrolyte transport; phenols; toxicant screening; toxin metabolism

The ability to transport solutes across epithelial membranes is vital for the function of many organs, e.g., secretion and reabsorption by the kidney. In turn, epithelial transport depends upon the coordinated function of individual transport systems located at opposite poles of the cells in the apical (BBM) and basolateral (BLM) membranes. Many of these membrane processes, particularly for anions, are not yet understood. Furthermore, because of their complex organization, functional importance, and exposed location, epithelial membranes are particularly susceptible to toxic effects of foreign chemicals. Our major recent emphasis has been on increasing our understanding of vectorial solute transport in polar epithelia, including the properties of specific carrier systems, the driving forces energizing transport, the regulation of transport events, and the coupling between events at opposite poles of the cells. Results for both organic (glucose, amino acids, organic acids) and inorganic (Na&, Cl minus, S04=) solutes emphasize the complexity of the chains of events which lead to active solute transport by epithelia and thus indicate that there are multiple sites for potential disruption by xenobiotics. Moreover, they also show that similar chains are responsible for transport of widely different solutes; thus, that the same mechanism may be responsible for breakdown in transport of unrelated solutes. For example, the organic cation, L-lysine, and the inorganic anion S04=, were shown to be transported via pH gradient-dependent mechanisms. Therefore, transport of both solutes could be markedly inhibited by the protonophore, pentachlorophenol, which collapses the pH gradient across the membrane.

跨上皮膜运输溶质的能力对于 许多器官的功能，例如，分泌和重吸收 肾。 反过来，上皮运输取决于协调 位于相反极点的单个运输系统的功能 顶端（BBM）和基底外侧（BLM）膜中的细胞。 其中许多 尚未了解膜过程，尤其是对于阴离子。 此外，由于其复杂的组织，功能重要性， 和暴露的位置，上皮膜特别容易受到 外国化学物质的有毒作用。 我们最近的重点一直在 增进我们对极地矢量溶质传输的理解 上皮，包括特定载体系统的特性， 驱动力量运输，运输事件的调节， 以及细胞相对极点的事件之间的耦合。 结果 对于有机（葡萄糖，氨基酸，有机酸）和无机（Na＆，， Cl Minus，S04 =）溶液强调了事件链的复杂性 这导致上皮的主动溶质传输，因此表明 异种生物有多个潜在破坏的地点。 此外，他们还表明类似的连锁店负责运输 溶质差异很大；因此，相同的机制可能是 负责无关溶质运输的分解。 例如， 有机阳离子，l赖氨酸和无机阴离子S04 =，显示为 通过pH梯度依赖机制运输。 因此，运输 两种溶质都可以被质子团显着抑制 五氯苯酚，使pH梯度跨越了整个膜。