NHE-3 基因缺陷小鼠肾集合管中 HCO-3 的重吸收：一种代偿反应。
HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response.
作者信息
Nakamura S, Amlal H, Schultheis P J, Galla J H, Shull G E, Soleimani M
机构信息
Department of Internal Medicine, Biochemistry and Microbiology, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267, USA.
出版信息
Am J Physiol. 1999 Jun;276(6):F914-21. doi: 10.1152/ajprenal.1999.276.6.F914.
Mice with a targeted disruption of Na+/H+ exchanger NHE-3 gene show significant reduction in HCO-3 reabsorption in proximal tubule, consistent with the absence of NHE-3. Serum HCO-3, however, is only mildly decreased (P. Schulties, L. L. Clarke, P. Meneton, M. L. Miller, M. Soleimani, L. R. Gawenis, T. M. Riddle, J. J. Duffy, T. Doetschman, T. Wang, G. Giebisch, P. S. Aronson, J. N. Lorenz, and G. E. Shull. Nature Genet. 19: 282-285, 1998), indicating possible adaptive upregulation of HCO-3-absorbing transporters in collecting duct of NHE-3-deficient (NHE-3 -/-) mice. Cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) were perfused, and total CO2 (net HCO-3 flux, JtCO2) was measured in the presence of 10 microM Schering 28080 (SCH, inhibitor of gastric H+-K+-ATPase) or 50 microM diethylestilbestrol (DES, inhibitor of H+-ATPase) in both mutant and wild-type (WT) animals. In CCD, JtCO2 increased in NHE-3 mutant mice (3.42 +/- 0.28 in WT to 5.71 +/- 0.39 pmol. min-1. mm tubule-1 in mutants, P < 0.001). The SCH-sensitive net HCO-3 flux remained unchanged, whereas the DES-sensitive HCO-3 flux increased in the CCD of NHE-3 mutant animals. In OMCD, JtCO2 increased in NHE-3 mutant mice (8.8 +/- 0.7 in WT to 14.2 +/- 0.6 pmol. min-1. mm tubule-1 in mutants, P < 0.001). Both the SCH-sensitive and the DES-sensitive HCO-3 fluxes increased in the OMCD of NHE-3 mutant animals. Northern hybridizations demonstrated enhanced expression of the basolateral Cl-/HCO-3 exchanger (AE-1) mRNA in the cortex. The gastric H+-K+-ATPase mRNA showed upregulation in the medulla but not the cortex of NHE-3 mutant mice. Our results indicate that HCO-3 reabsorption is enhanced in CCD and OMCD of NHE-3-deficient mice. In CCD, H+-ATPase, and in the OMCD, both H+-ATPase and gastric H+-K+-ATPase contribute to the enhanced compensatory HCO-3 reabsorption in NHE-3-deficient animals.
靶向破坏钠/氢交换体NHE - 3基因的小鼠，其近端小管中碳酸氢根（HCO₃⁻）重吸收显著减少，这与NHE - 3的缺失一致。然而，血清HCO₃⁻仅轻度降低（P. 舒尔蒂斯、L. L. 克拉克、P. 梅内顿、M. L. 米勒、M. 索莱马尼、L. R. 加韦尼斯、T. M. 里德尔、J. J. 达菲、T. 多奇曼、T. 王、G. 吉比施、P. S. 阿隆森、J. N. 洛伦兹和G. E. 舒尔。《自然遗传学》19: 282 - 285, 1998），这表明在NHE - 3缺陷（NHE - 3 -/-）小鼠的集合管中，HCO₃⁻吸收转运体可能发生了适应性上调。对皮质集合管（CCD）和外髓集合管（OMCD）进行灌注，并在10微摩尔的先灵葆雅28080（SCH，胃H⁺ - K⁺ - ATP酶抑制剂）或50微摩尔己烯雌酚（DES，H⁺ - ATP酶抑制剂）存在的情况下，测量突变型和野生型（WT）动物的总二氧化碳（净HCO₃⁻通量，JtCO₂）。在CCD中，NHE - 3突变小鼠的JtCO₂增加（WT为3.42±0.28，突变体为5.71±0.39皮摩尔·分钟⁻¹·毫米小管⁻¹，P < 0.001）。SCH敏感的净HCO₃⁻通量保持不变，而DES敏感的HCO₃⁻通量在NHE - 3突变动物CCD中增加。在OMCD中，NHE - 3突变小鼠的JtCO₂增加（WT为8.8±0.7，突变体为14.2±0.6皮摩尔·分钟⁻¹·毫米小管⁻¹，P < 0.001）。在NHE - 3突变动物的OMCD中，SCH敏感和DES敏感的HCO₃⁻通量均增加。Northern杂交显示皮质中基底外侧Cl⁻/HCO₃⁻交换体（AE - 1）mRNA表达增强。胃H⁺ - K⁺ - ATP酶mRNA在NHE - 3突变小鼠的髓质中上调，但在皮质中未上调。我们的结果表明，NHE - 3缺陷小鼠的CCD和OMCD中HCO₃⁻重吸收增强。在CCD中，H⁺ - ATP酶，在OMCD中，H⁺ - ATP酶和胃H⁺ - K⁺ - ATP酶都有助于NHE - 3缺陷动物中增强的代偿性HCO₃⁻重吸收。
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