TRANSPORT CHARACTERISTICS IN SPECIFIC RENAL CELL TYPES

特定肾细胞类型的转运特征

• 批准号: 3230913
• 负责人: STEPHEN H WRIGHT
• 金额: $ 7.27万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230913
• 关键词: adenosine triphosphate; basolateral membrane; brush border membrane; cell type; dicarboxylate; glucose; ion transport; kidney cell; lithium; membrane permeability; membrane potentials; proline; renal cortex; renal tubular transport; stoichiometry; succinates; tissue /cell culture

We propose to study the mechanism(s) of organic cation transport in thearenal proximal tubule. Organic cations (and by extension, organic bases; OC's) represent a diverse set of physiologically important compounds, including molecules such as choline, epinephrine, and N1-methylnicotinamide (NMN). OC's also include a number of drugs, such as cimetidine, procainamide, and tetraethylammonium(TEA). The processes of renal tubular secretion and reabsorption are presumed to play an important role in regulating the plasma concentration of a number of these compounds. However, comparatively little is known about the mechanism of tubular transport of OC's. Currently there is conflicting evidence concerning the nature of the processes responsible for the transepithelial transport of OC's; some studies suggest that the lumenal membrane of the proximal tubular cell plays the active role in OC secretion, while the pertubular membrane play a passive role; other data suggest that the pertubular membrane is the site of active OC transport, and that the lumenal membrane is passive. We have preliminary data suggesting that both the lumenal and peritubular membranes of the rabbit proximal tubule have active transport processes which serve to facilitate the secretion of OC's. We propose to extend these studies by examining OC transport using several different "levels" of cellular organization, each of which offers unique advantages to the study of transport processes: i) isolated membranes, which permit both the detailed examination of kinetic mechanisms under carefully controlled conditions, and the large-scale screening of many compounds in studies of structural specificity; ii) isolated cells and tubules, which permit simultaneous examination of the transport contributions of both lumenal and peritubular membranes, as well as the study of links between transport and metabolism; and iii) perfused proximal tubules, which offer the opportunity to study lumenal and peritubular transport working in series to produce transepithelial fluxes. The integrated use of these three methodologies will permit us to formulate and test detailed hypotheses concerning the mechanism of proximal tubular OC transport. We hope to develop a model for renal tubular OC transport that will both aid in understanding the role of the kidney in regulation of plasma levels of these compounds, and increase our general understanding of epithelial secretory processes.

我们建议研究有机阳离子在土壤中的迁移机制。 肾近端小管 有机阳离子（以及通过扩展，有机阳离子） 碱基（OC）代表了多种生理学上重要的 化合物，包括分子如胆碱、肾上腺素和 N1-甲基烟酰胺（NMN）。 OC还包括一些药物，如 西咪替丁、普鲁卡因胺和四乙铵（TEA）。 的过程 肾小管的分泌和重吸收被认为是重要的 在调节许多这些药物的血浆浓度中的作用 化合物. 然而，相对而言，人们对 OC的管状运输。 目前有相互矛盾的证据 关于负责跨上皮的过程的性质， OC的运输;一些研究表明， 近曲小管上皮细胞在OC分泌中起积极作用， pertubular膜发挥被动作用;其他数据表明， 穿管膜是活性OC转运的位点， 腔膜是被动的。 我们有初步数据表明 兔近曲小管的管腔膜和管周膜具有 主动运输过程，有助于促进分泌 OC的。 我们建议扩展这些研究，研究OC运输， 细胞组织的几个不同的“层次”，每一个层次都提供了 独特的优势，运输过程的研究：i）孤立 膜，它允许详细检查动力学机制 在严格控制的条件下， 结构特异性研究中的许多化合物; ii）分离的细胞， 小管，允许同时检查运输 管腔和管周膜的贡献，以及 研究运输和代谢之间的联系;和iii）灌注近端 小管，这提供了研究管腔和管周的机会 运输串联工作以产生跨上皮通量。 的 综合使用这三种方法将使我们能够制定和 测试有关近端肾小管OC机制的详细假设 运输 我们希望开发一种肾小管OC转运模型， 将有助于了解肾脏在调节 这些化合物的血浆水平，并增加我们对 上皮分泌过程。