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Regulation of acid secretion in cortical collecting duct : An Effect Mediated by Hensin.

皮质集合管酸分泌的调节：由 Hensin 介导的效应。

基本信息

批准号：
14571032
负责人：
TSURUOKA Shuichi
金额：
$ 2.24万
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 (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571032/
关键词：
collecting duct Hensin metabolic acidosis anion exchanger cyclosporine A Drug adverse reactions 重炭酸

项目摘要

Metabolic acidosis causes a reversal of polarity of HCO(3)(-) flux in the cortical collecting duct(CCD). In CCDs incubated in vitro in acid media, beta-intercalated (HCO(3)(-)-secreting) cells are remodeled to functionally resemble alpha-intercalated (H(+)-secreting) cells. A similar remodeling of beta-intercalated cells, in which the polarity of H(+) pumps and Cl(-)/HCO(3)(-) exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO(3)(-) flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same beta-intercalated cells before and after acid incubation and found that apical Cl/HCO(3) exchange was abolished following acid incubation. Some cells also developed basolateral Cl(-)/HCO(3)(-) exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of beta-intercalated cells. Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl(-)/HCO(3)(-) exchange observed in the same cells and the corresponding suppression of HCO(3)(-) secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting beta-intercalated cells. Hence, the adaptive conversion of beta-intercalated cells to alpha-intercalated cells during acid incubation depends upon ECM-associated hensin.

代谢性酸中毒导致皮质收集管内HCO(3)(-)通量的极性颠倒。在酸性介质中体外培养的CDs中，β-嵌入(HCO(3)(-)-分泌)细胞被重塑为功能类似于α-嵌入(H(+)-分泌)细胞。在细胞培养中也会发生类似的β-插层细胞重塑，其中H(+)泵和Cl(-)/HCO(3)(-)交换器的极性颠倒，需要在ECM中沉积聚合的Hensin。在体外低pH条件下保持3h的CCDs表现出HCO(3)(-)通量的逆转，这在数量上与先前在体内观察到的酸处理的兔的效果相似。我们在酸培养前后跟踪相同β-插层细胞的细胞内pH，发现酸培养后顶端的氯/HCO(3)交换被取消。一些细胞还发生了基侧Cl(-)/HCO(3)(-)交换，表明嵌入细胞的极性发生了逆转。这种适应需要完整的微管和微丝，以及新的蛋白质合成，并与β-嵌入细胞顶面尺寸的减小有关。加入抗Hensin抗体可阻止酸诱导的同一细胞顶端和基底侧端的Cl(-)/HCO(3)(-)交换的改变，以及相应的HCO(3)(-)分泌的抑制。酸负荷也促进了细胞外基质中Hensin在适应的β-嵌入细胞中的沉积。因此，在酸孵育过程中，β-嵌入细胞向α-嵌入细胞的适应性转化依赖于细胞外基质相关的Hensin。