Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule.
Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule.
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DOI：
10.1152/ajprenal.2001.281.2.f288
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发表时间：
2001-08
期刊：
影响因子：
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通讯作者：
Tong Wang;Chao-Ling Yang;T. Abbiati;G. Shull;Gerhard Giebisch;Peter S. Aronson
中科院分区：
文献类型：
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作者：
Tong Wang;Chao-Ling Yang;T. Abbiati;G. Shull;Gerhard Giebisch;Peter S. Aronson
甲酸盐显著地促进了近端小管对NaCl的吸收。这种对NaCl转运的刺激符合一个细胞模型，该模型涉及Cl(-)-甲酸交换，同时由于甲酸的非离子扩散或H(+)-甲酸共转运导致ph偶联甲酸再循环。甲酸盐的循环过程需要H（+）的分泌。虽然Na(+)-H（+）交换异构体NHE3在近端小管中占H（+）分泌的最大组成部分，但在NHE3缺失的小鼠中，HCO吸收率或细胞H（+）挤出率仍保持40-50%。本研究的目的是利用NHE3缺失小鼠，直接测试根尖膜NHE3在介导甲酸刺激的NaCl吸收中的作用。研究表明，甲酸盐刺激小鼠体内近端微灌注的NaCl吸收，但在NHE3缺失的小鼠中不存在甲酸盐刺激的NaCl吸收成分。相比之下，草酸刺激的NaCl吸收在NHE3缺失小鼠中得以保留，这表明草酸刺激的NaCl吸收与Na(+)-H（+）交换无关。甲酸诱导的NaCl吸收几乎完全依赖于NHE3活性，这提高了NHE3和甲酸转运体在刷状膜上功能偶联的可能性。
The absorption of NaCl in the proximal tubule is markedly stimulated by formate. This stimulation of NaCl transport is consistent with a cell model involving Cl(-)-formate exchange in parallel with pH-coupled formate recycling due to nonionic diffusion of formic acid or H(+)-formate cotransport. The formate recycling process requires H(+) secretion. Although Na(+)-H(+) exchanger isoform NHE3 accounts for the largest component of H(+) secretion in the proximal tubule, 40-50% of the rates of HCO absorption or cellular H(+) extrusion persist in NHE3 null mice. The purpose of the present investigation is to use NHE3 null mice to directly test the role of apical membrane NHE3 in mediating NaCl absorption stimulated by formate. We demonstrate that formate stimulates NaCl absorption in the mouse proximal tubule microperfused in vivo, but the component of NaCl absorption stimulated by formate is absent in NHE3 null mice. In contrast, stimulation of NaCl absorption by oxalate is preserved in NHE3 null mice, indicating that oxalate-stimulated NaCl absorption is independent of Na(+)-H(+) exchange. The virtually complete dependence of formate-induced NaCl absorption on NHE3 activity raises the possibility that NHE3 and the formate transporters are functionally coupled in the brush border membrane.