RENAL HANDLING OF ORGANIC IONS

本计划项目的长期目标是了解-1) 有机阳离子(或)肾小管转运机制 碱基)，2)有机物肾小管转运机制 阴离子(或酸)，尤其是与尿酸转运有关的 结石形成；3)生理和心理调节。 通过这些途径运输的重要药理分子；4) 通过这些途径运输的分子可能产生的毒性影响； 5)肾脏毒物干扰这些过程的过程 小路。研究战略涉及以下方面的综合方法 使用代表不同级别的系统的四个单独项目 生物组织--从整个动物到细胞膜 并使用了各种各样的技术。几个物种(或来自 几种)哺乳动物--兔、鼠、猪和非哺乳动物-- 蛇和鸡--物种将被用来利用 在不同的物种中具有夸张的功能或易于准备。 具体制剂，反映生物组织的水平，以 使用的是整个动物(项目2和项目4)、肾脏切片(项目 #3)，分离的肾小管(项目01、*2、*3和*4)， 培养(项目*2和*3)和肾膜小泡(项目01， 02和04)。主要技术或实验设计将 项目包括：清除研究(项目2和项目4)；放射性示踪剂 运输研究(项目1、2、3和4)；组织学， 转运或毒性的组织化学和超微结构分析 (项目03和04)；细胞内浓度的测量 有机离子的同位素标记技术(项目*1、*2和*3) 以及离子选择性微电极对细胞内活性的影响 (项目*1和*2)；测量运输和运输的光学程序 细胞内pH和PCA(项目*I、*2和*3)；以及使用 具有不同化学结构的化合物用于检测其特异性 和载体的化学结构，并用于分离和鉴定 它们(项目*1和*2)或用于探测毒性影响的特异性 (项目01、02和*3)。

The long-term objectives of this Program Project are to understand- 1) the mechanisms involved in renal tubular transport of organic cations (or bases), 2) the mechanisms involved in renal tubular transport of organic anions (or acids), particularly the transport of uric acid in relation to stone formation; 3) the regulation of physiologically and pharmacologically important molecules transported by these pathways; 4) the possible toxic effects of molecules transported by these pathways; and 5) the processes by which renal toxicants interfere with these pathways. The research strategy involves an integrated approach among four individual projects using systems that represent different levels of biological organization -- from the whole animal to the cell membrane -- and using a wide variety of techniques. Several species (or tissue from several species) of mammalian--rabbit, rat, and pig and nonmammalian-- snake and chicken -- species will be employed to take advantage of exaggerated function or ease of preparation in different species. Specific preparations, reflecting levels of biological organization, to be used are whole animals (Projects #2 and #4), kidney slices (Project #3), isolated renal tubules (Projects 01, *2, *3, and *4), renal cells in culture (Projects *2 and *3), and renal membrane vesicles (Projects 01, 02, and 04). Major techniques or experimental designs linking the projects include: clearance studies (Projects #2 and *4); radiotracer studies of transport (Projects *I, *2, *3, and #4); histological, histochemical, and ultrastructural analyses of transport or toxicity (Projects 03 and 04); measurements of intracellular concentrations of organic ions by isotopic labeling techniques (Projects *1, *2, and *3) and of intracellular activities by ion-selective microelectrodes (Projects *1 and *2); optical procedures for measuring transport and intracellular pH and pCa (Projects *I, *2, and *3); and the use of compounds with different chemical structures for probing the specificity and chemical structure of the carriers and for isolating and identifying them (Projects *1 and *2) or for probing specificity of toxic effects (Projects 01, 02, and *3).