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Roles of Na-transporter genes in disorders of electrolyte metabolism

钠转运蛋白基因在电解质代谢紊乱中的作用

基本信息

批准号：
09470239
负责人：
ASANO Yasushi
金额：
$ 8.58万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

We used cultured vascular smooth muscle cells (VSMC) and kidney cells to determine the roles of Na-transporters (Na pump, Na/H exchanger, and epithelial Na channel) in the disorders of salt balance. The results were in the following:1) In VSMC, serum, hyperosmolality (induced by mannitol and glucose), corticosterone and its metabolite, 11-dehydrocorticosterone, differentially stimulated Na pump αl-and β1-mRNA expression, α- and β1-subunit protein expression, and Na, K-ATPase activity; 2) Low Na diet (elevated endogenous aldosterone levels) increased epithelial Na channel α subunit mRNA levels from inner medulla of the rat kidneys, but did not affect β or γ subunit mRNA levels; 3) In the rabbit cortical collecting duct (CCD), acute elevation of basolateral K concentrations from 2.5 to 8.5 mM activated the basolateral Na pump, which secondarily elevates the apical Na and K conductances. DOCA pretreatment increased the basolateral K conductances and augmented the response to the rise of K of both the basolateral Na pump activity and the apical cation conductances. Luminal Na concentration, probably by changes in cell Na concentrations, modulated the tight coupling between the basolateral Na pump and apical cation conductances; 4) In the CCD from control rabbits, raising luminal Na concentrations from 14 to 147 mM activated basolateral Na pump and apical Na and K conductances via increased cell Na concentration. The luminal Na-dependent activation of the basolateral pump and the apical cation conductances was sharply enhanced in the CCD from DOCA-treated rabbits. Chronic DOCA pretreatment also increased basolateral K conductance upon raising luminal Na concentration; 5) In VSMC, aldosterone activated Na/H exchange (NHE) by nongenomic and genomic mechanisms; 6) Incubation of OKP cells in low-K media increased NHE3 activity after early decrease in intracellular PH; and 7) Extracellular Cl modulated shrinkage-induced activation of NHE in rat renal mesangial cells.

我们利用培养的血管平滑肌细胞(VSMC)和肾脏细胞来确定钠转运体(Na泵、Na/H交换器和上皮性Na通道)在盐平衡紊乱中的作用。结果如下：1)血清、高渗透压(甘露醇和葡萄糖诱导)、皮质酮及其代谢产物11-脱氢皮质酮对大鼠肾小管上皮细胞Na泵α-和β-1基因表达、α-和β1-亚单位蛋白表达以及Na，K-α酶活性有不同程度的刺激作用：2)低钠饮食(内源性醛固酮水平升高)可增加大鼠肾脏内髓上皮细胞Na通道β和γ亚单位基因表达，但不影响其表达水平；3)在兔皮质集合管中，基底侧K浓度从2.5 mM急升至8.5 mM时，激活了基侧Na泵，继而使心尖Na、K电导升高。DOCA处理增加了基侧K电导，增强了基侧Na泵活性和顶端阳离子电导对K升高的响应。腔内钠浓度，可能是通过细胞钠浓度的变化，调节基础侧钠泵和心尖阳离子电导之间的紧密耦合；4)在对照组兔的CCD中，通过增加细胞钠浓度，使腔内钠浓度从14 mM增加到147 mM，激活的基础侧钠泵和心尖Na和K电导增加。经DOCA处理后的兔眼，基底侧泵和根尖阳离子电导的腔内钠依赖性激活显著增强。在VSMC中，醛固酮通过非基因组和基因组机制激活Na/H交换(NHE)；6)低钾培养的OKP细胞在细胞内pH早期下降后增加NHE3的活性；以及7)细胞外氯调节收缩诱导的大鼠肾系膜细胞NHE的激活。