Investigation on electrolyte transport in the renal tubule by using knockout mice

在野生型（WT）小鼠和敲除mdrla和mdrlb基因的小鼠（KO）中，研究了p-糖蛋白（P-gp）在细胞体积调节中的作用以及基底侧Na/H交换（NHE）在P-gp诱导的细胞体积调节中的作用。结果如下：1。在小鼠近端小管中，P-gp调节高渗甘露醇应激时的调节性体积增加（RVI），但不调节低渗应激时的调节性体积减少。基底外侧膜NHE部分参与高渗应激下P-gp诱导的RVI调节。在暴露于高渗尿素的两组小管中，细胞体积的减少较小且是短暂的，小管立即恢复到其控制体积。暴露于高渗甘露醇溶液期间，p- gp诱导的RVI调节是通过PKC.5介导的。微管、微丝和wortmaninin敏感、LY 294002不敏感的磷脂酰肌醇3-激酶参与pkc诱导的rvi。在没有P-gp活性的情况下，高渗甘露醇通过PKC激活基底外侧NHE，而在P-gp活性存在的情况下，它不会。高渗尿素在WT和KO小鼠的近端小管中通过酪氨酸激酶激活基底侧NHE。

The role of P-glycoprotein(P-gp) in cell volume regulation and the involvement of the basolateral Na/H exchange(NHE) in the P-gp-induced cell volume regulation were examined in isolated nonperfused proximal tubule S2 segments from wild-type (WT) mice and those (KO) in which both the mdrla and mdrlb genes were knocked out. The results were in the following :1.In the mouse proximal tubule, P-gp modulates regulatory volume increase(RVI) during hyperosmotic mannitol stress, but not regulatory volume decrease during hyposmotic stress.2.The basolateral membrane NHE partly contributes to the P-gp induced modulation of RVI under the hyperosmotic stress.3.In both groups of the tubules exposed to hyperosmotic urea, the reduction in cell volume was smaller and transient, tubules returning to their control volume immediately.4.P-gp-induced modulation of RVI during the exposure to the hyperosmotic mannitol solution is mediated via PKC.5.The microtubule, microfilament, and wortmannin-sensitive, LY 294002-insensitive phosphatidylinositol 3-kinase contribute to the PKC-induced RVI.6.In the absence of P-gp activity, the hyperosmotic mannitol activates basolateral NHE via PKC, whereas in the presence of P-gp activity, it does not.7.The hyperosmotic urea activates basolateral NHE via tyrosine kinase in the proximal tubules from both WT and KO mice.