AMINO ACID TRANSPORT BY THE PROXIMAL TUBULE

对肾脏氨基酸转运的直接表征主要是 仅限于近曲小管(S-1)(23，27，28)。氨基酸 近端直小管转运研究(1，2，3，22)(S-2) 已经很少了，而且没有关于晚期近端直的信息 小管(S-3)氨基酸的处理。此外，目前还不清楚如何 许多独立的氨基酸转运机制存在于近端。 如果某些氨基酸具有共同的转运机制，或者如果 共用机制的位置在管腔膜或基底外侧 膜(11，12，28，32)。本研究旨在直接回答这些问题。 用兔离体灌注型肾单位提问。货物的运输 S-1、S-2和S-3片段中的4个氨基酸将被研究 近端小管。要研究的氨基酸是精氨酸、天冬氨酸 酸、丙氨酸和脯氨酸，每种都代表一种比例的氨基酸 输运体系，即二元、酸性、中性和亚米诺， 分别进行了分析。将确定这些氨基酸是否代表 S一号、S二号和S三号三段不同的转运机制 近端小管的(3，31)及其转运的定量 每个段的J-max、K-m和泄漏(K)特性。其他氨基酸 据报道，它们与体内的氨基酸具有相同的转运机制 将对研究进行测试，以确定共享交通站点是否位于 在管腔膜上的入口台阶或在基底外侧的出口台阶 薄膜。此外，还将确定活动站点是否为 跨上皮吸收转运位于管腔或 基底侧膜。基侧膜对氨基酸的摄取 在近端小管的三段管周积液中 检查过了。甘氨酸的基侧隔离已被观察到 首席调查员(3)。如果这是 近端直小管可解释某些氨基酸的分泌 病态环境。最后，所有这些信息，即轴向 沿肾单位(J-max、K-m和k)和部位的转运分布 氨基酸相互作用，将被合并到一个模型中来解释 肾单位中回收几乎100%过滤的氨基酸的机制 酸。

Direct characterization of renal amino acid transport has been mainly restricted to the proximal convoluted tubule (S-1)(23,27,28). Amino acid transport studies (1,2,3,22) in the proximal straight tubule (S-2) have been few and no information is available on the late proximal straight tubules (S-3) handing of amino acids. In addition, it is not clear how many independent amino acids transport mechanisms exist along the proximal tubule and if some amino acids share transport mechanisms, or if the location of a shared mechanism is at the luminal membrane or basolateral membrane (11,12,28,32). This study is designed to directy answer these questions using the rabbit isolated perfused nephron. The transport of four amino acids will be studied in the S-1, S-2, and S-3 segments of the proximal tubule. The amino acids to be studied are arginine, aspartic acid, alanine and proline, each representing a proported amino acid transport system, namely, dibasic, acidic, neutral and imino, respectively. It will be determined if these amino acids represent different transport mechanisms in all three segments (S-1, S-2 and S-3) (3,31) of the proximal tubule as well as quantitate their transport characteristics J-max, K-m and leak (k) in each segment. Other amino acids that are reported to share transport mechanisms with the amino acid in this study will be tested to determine if the shared transport site is located at the entry step on the luminal membrane or exit step at basolateral membrane. In addition, it will be determined if the active site for transepithelial absorptive transport is located at the luminal or basolateral membrane. Uptake of amino acids by the basolateral membrane from peritubular fluid in the three segments of the proximal tubule will be examined. Basolateral sequestering of glycine has been observed by the principal investigator (3). If this is a general characteristic for the proximal straight tubule it could explain amino acid secretion in some pathological settings. Finally, all this information, namely, axial distribution of transport along the nephron (J-max, K-m, and k) and sites of amino acid interaction, will be incorporated into a model to explain the mechanisms in the nephron that reclaim nearly 100% of the filtered amino acids.