ROLE OF ALTERED MEMBRANE FUNCTION IN XENOBIOTIC TOXICITY

跨上皮膜运输溶质的能力对 器官的功能许多器官的功能，例如 肾脏。反过来，上皮细胞的运输依赖于协调的 位于铁路两极的各个运输系统的功能 根尖膜(BBM)和基底侧膜(BLM)中的细胞。其中许多 膜过程，特别是阴离子的膜过程，目前还不清楚。 此外，由于其组织复杂、功能重要， 和暴露位置，上皮膜特别容易受到 外国化学品的毒害作用。我们最近的主要重点是 加深我们对极地矢量溶质输运的理解 上皮细胞，包括特定载体系统的属性， 为运输注入活力的驱动力，运输活动的监管， 以及电池相反极处的事件之间的耦合。结果 有机(葡萄糖、氨基酸、有机酸)和无机(Na&， CL-，S04=)溶质强调了事件链的复杂性 这导致了上皮细胞对溶质的主动运输，从而表明 有多个位置可能会受到外源生物的破坏。 此外，它们还表明，类似的链条负责运输 完全不同的溶质；因此，相同的机理可能是 负责无关溶质运输过程中的故障。例如, 有机阳离子L-赖氨酸和无机阴离子S04=分别为 通过依赖于pH梯度的机制进行运输。因此，运输 这两种溶质都能被原载体显著抑制， 五氯苯酚，它使膜上的pH梯度崩溃。

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.