NA+ AND CL- TRANSPORT IN THE MAMMALIAN PROXIMAL TUBULE

描述（改编自申请人的摘要）： 近端小管的功能是吸收NaCl。 甲酸盐、PTH和 血管紧张素II是近端小管NaCl转运的有效调节剂。 近端直小管中甲酸盐对NaCl转运的调节 目前认为是由顶端Cl-/甲酸盐交换介导的， Na +/H+交换与顶端甲酸再循环。 然而，运输 兔近端直小管的特性，其特征在于 实验室不支持这种模式。 在家兔浅表S2近端 直小管，顶端Cl-/碱交换发生在没有外源性 甲酸盐和碳酸氢盐，并刺激Na+去除。 数据表明 这种转运蛋白以Cl/OH-模式运作。 Na+去除似乎 通过细胞内Ca 2+的变化调节顶端Cl-/碱交换。 S2 肾小管甲酸盐产生和血液甲酸盐浓度太低， 允许显著的顶端蚁酸再循环，但通常认为， 管腔甲酸盐刺激跨上皮NaCl吸收。 在这 建议，主要研究者的数据表明，鲁米那 甲酸盐直接刺激顶端Na +/H+交换活性。 的 主要研究者还显示，PTH和AII调节 近端直肌中的顶侧/基底侧阴离子交换和Cl-转运 小管 本提案将检验以下假设：1） 顶端NaCl吸收主要通过Na +/H+交换介导， Cl-/碱交换; 2）Na+去除通过以下途径调节顶端Cl-/碱交换： 通过钙调素依赖性机制增加细胞内Ca2 +; 3） 管腔甲酸盐通过刺激血管内皮细胞增加跨上皮NaCl转运， 顶端Na +/H+交换，而不是通过甲酸盐依赖的Cl-/碱交换; 4） 基底外侧甲酸盐通过刺激血管内皮细胞的生长， 甲状旁腺素和AII调节顶侧和底侧Na +/H+交换， 近端小管中的基底侧阴离子交换和Cl-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.