NA+ AND CL- TRANSPORT IN THE MAMMALIAN PROXIMAL TUBULE

描述(改编自申请人的摘要)：主要的 近端小管的功能是吸收盐分。甲酸盐、PTH和 血管紧张素II是近端小管氯化钠转运的有力调节者。 甲酸盐对近曲小管内氯化钠转运的调节 目前认为是由偶联的顶端氯-/甲酸盐交换所介导的 Na/H交换，顶端甲酸循环。然而，交通工具 兔近端直小管的特性 实验室不支持此模型。在兔浅层S2近端 直小管，顶端氯-/碱交换发生在没有外源的情况下 甲酸盐和碳酸氢盐，并被钠的去除刺激。数据表明 这种转运蛋白以氯/羟基-模式工作。去掉NA似乎会 通过改变细胞内的钙离子来调节顶端的氯离子/碱交换。S_2 小管甲酸盐产生和血液甲酸盐浓度太低 允许大量的根尖甲酸回收，但人们普遍同意 甲酸鲁米那促进跨上皮氯化钠吸收。在这 提案中，首席调查员的数据表明，卢米纳 甲酸盐直接刺激心尖部Na/H交换活性。这个 首席研究人员还表明，甲状旁腺素和AII调节 近侧直根尖/底外侧阴离子交换与氯离子转运 小管。本提案将检验以下假设：1) 顶端的盐吸收主要由Na/H交换偶联到 Cl-/碱交换；2)钠的清除通过以下途径调节顶端的氯/碱交换 通过钙调素依赖机制增加细胞内钙；3) 甲酸鲁米那通过刺激血管内皮细胞对氯化钠的转运 顶端Na/H交换，而不是通过依赖甲酸盐的Cl-/碱交换；4) 基底侧甲酸盐通过刺激减少跨上皮氯化钠转运 5)甲状旁腺素和一氧化氮合酶调节心尖部和心尖部。 近端小管的基侧阴离子交换和氯离子转运。

DESCRIPTION (Adapted from the Applicant's Abstract): One of the primary functions of the proximal tubule is to absorb NaCl. Formate, PTH and angiotensin II are potent regulators of proximal tubule NaCl transport. Regulation of NaCl transport by formate in the proximal straight tubule is currently believed to be mediated by apical Cl-/formate exchange coupled to Na+/H+ exchange with apical formic acid recycling. However, the transport properties of the rabbit proximal straight tubule characterized by their laboratory do not support this model. In the rabbit superficial S2 proximal straight tubule, apical Cl-/base exchange occurs in the absence of exogenous formate and bicarbonate, and is stimulated by Na+ removal. The data suggest that this transporter functions in a Cl/OH- mode. Na+ removal appears to regulate apical Cl-/base exchange via a change in intracellular Ca2+. S2 tubule formate production and blood formate concentration are too low to permit significant apical formic recycling yet it is generally agreed that luminal formate stimulates the transepithelial NaCl absorption. In this proposal, the data by the principal investigator demonstrates that luminal formate stimulates the apical Na+/H+ exchange activity directly. The principal investigator also shows evidence that PTH and AII regulate apical/basolateral anion exchange and Cl- transport in the proximal straight tubule. The following hypotheses will be tested in this proposal: 1) apical NaCl uptake is mediated predominantly by Na+/H+ exchange coupled to Cl-/base exchange; 2) Na+ removal regulates apical Cl-/base exchange through an increase in intracellular Ca2+ via a calmodulin-dependent mechanism; 3) Luminal formate increases transepithelial NaCl transport by stimulating the apical Na+/H+ exchange and not via formate-dependent Cl-/base exchange; 4) Basolateral formate decreases transepithelial NaCl transport by stimulating the basolateral Na+/H+ exchange; and 5) PTH and AII regulate apical and basolateral anion exchange and Cl- transport in the proximal tubule.