Kurtz I, Nagami G, Yanagawa N, Li L, Emmons C, Lee I
Division of Nephrology, School of Medicine, University of California, Los Angeles 90024.
J Clin Invest. 1994 Jul;94(1):173-83. doi: 10.1172/JCI117304.
The present study was undertaken to determine the magnitude and mechanism of base transport via the apical and basolateral Na(+)-independent Cl-/base exchangers in rabbit isolated perfused superficial S2 proximal tubules. The results demonstrate that there is an apical Na(+)-independent Cl-/base exchanger on both membranes. HCO3- fails to stimulate apical Cl-/base exchange in contrast to the basolateral exchanger. Inhibition of endogenous HCO3- production does not alter the rate of apical Cl-/base exchange in Hepes-buffered solutions. Both exchangers are inhibited by H2DIDS and furosemide; however, the basolateral anion exchanger is more sensitive to these inhibitors. The results indicate that the apical and basolateral Cl-/base exchangers differ in their transport properties and are able to transport base equivalents in the absence of formate. The formate concentration in rabbit arterial serum is approximately 6 microM and in vitro tubule formate production is < 0.6 pmol/min per mm. Formate in the micromolar range stimulates Jv in a dose-dependent manner in the absence of a transepithelial Na+ and Cl- gradient and without a measurable effect on Cl(-)-induced equivalent base flux. Apical formic acid recycling cannot be an important component of any cell model, which accounts for formic acid stimulation of transcellular NaCl transport in the rabbit superficial S2 proximal tubule. We propose that transcellular NaCl transport in this nephron segment is mediated by an apical Na+/H+ exchanger in parallel with a Cl-/OH- exchanger and that the secreted H+ and OH- ions form H2O in the tubule lumen.
本研究旨在确定兔离体灌注的浅表S2近端小管中通过顶端和基底外侧Na⁺非依赖性Cl⁻/碱基交换体进行碱基转运的程度和机制。结果表明，在这两种膜上均存在顶端Na⁺非依赖性Cl⁻/碱基交换体。与基底外侧交换体不同，HCO₃⁻不能刺激顶端Cl⁻/碱基交换。在Hepes缓冲溶液中，抑制内源性HCO₃⁻生成并不会改变顶端Cl⁻/碱基交换的速率。两种交换体均受H2DIDS和呋塞米抑制；然而，基底外侧阴离子交换体对这些抑制剂更为敏感。结果表明，顶端和基底外侧Cl⁻/碱基交换体的转运特性不同，并且在没有甲酸的情况下能够转运碱基当量。兔动脉血清中的甲酸浓度约为6微摩尔，体外小管甲酸生成量<0.6皮摩尔/分钟·毫米。在不存在跨上皮Na⁺和Cl⁻梯度且对Cl⁻诱导的当量碱基通量无明显影响的情况下，微摩尔范围内的甲酸以剂量依赖性方式刺激Jv。顶端甲酸循环不可能是任何细胞模型的重要组成部分，该模型解释了甲酸对兔浅表S2近端小管中跨细胞NaCl转运的刺激作用。我们提出，该肾单位节段中的跨细胞NaCl转运由顶端Na⁺/H⁺交换体与Cl⁻/OH⁻交换体并行介导，并且分泌的H⁺和OH⁻离子在小管腔中形成H₂O。
