Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice
Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice
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DOI：
10.1007/s00424-007-0318-z
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发表时间：
2008-01-01
影响因子：
4.5
通讯作者：
Soleimani, Manoocher
中科院分区：
文献类型：
--
作者：
Seidler, Ursula;Rottinghaus, Ingrid;Soleimani, Manoocher
PAT 1（Slc 26 a6）位于小肠绒毛的顶膜上，但其在盐吸收中的作用尚未研究。为了确定Slc 26 a6在空肠钠和氯吸收中的作用，以及其与NHE 3的相互作用，将来自Slc 26 a6 +/+和-/-以及NHE 3 +/+和-/-小鼠的肌肉剥离的空肠固定在Ussing室中，并测量电参数以及Cl-36（-）和Na-22（+）通量。在平行研究中，顶端Na+/H+交换器（NHE 3）的表达通过免疫荧光标记和免疫印迹分析在刷状缘膜（BBM）进行了检查。在基础状态下，净Cl-和Na+通量在Slc 26 a6-/-和+/+空肠中是吸收的，但在-/-动物中显著降低。在添加毛喉素后，在Slc 26 a6-/-和+/+空肠中，净Na+吸收减少，Isc强烈增加，净Cl-通量变为分泌。当加入鲁米那葡萄糖以激活Na+/葡萄糖共转运时，伴随的Cl+吸收在Slc 26 a6-/-空肠中显著减少，而Na+吸收在Slc 26 a6-/-和+/+空肠中增加到相同程度。在NHE 3缺乏空肠中的相同实验也显示Na+和Cl-吸收减少。结果进一步表明，NHE 3的缺乏使得Na（+）和Cl-吸收对cAMP的抑制无反应，但不影响葡萄糖驱动的Na+和Cl-吸收。免疫印迹显示在Slc 26 a6-/-和+/+小鼠的顶端膜中相当的NHE 3丰度和分布。这些数据有力地表明，Slc 26 a6在小肠中的电中性盐吸收中与NHE 3协同作用。Slc 26 a6还用于在葡萄糖驱动的盐吸收期间吸收Cl-。
PAT1 (Slc26a6) is located on the apical membrane of the small intestinal villi, but its role for salt absorption has not been studied. To ascertain the role of Slc26a6 in jejunal sodium and chloride absorption, and its interplay with NHE3, muscle-stripped jejuna from Slc26a6+/+ and -/- and NHE3 +/+ and -/- mice were mounted in Ussing chambers and electrical parameters, and Cl-36(-) and Na-22(+) fluxes were measured. In parallel studies, expression of the apical Na+/H+ exchanger (NHE3) was examined by immunofluorescence labeling and immunoblot analysis in brush border membrane (BBM). In the basal state, net Cl- and Na+ fluxes were absorptive in Slc26a6-/- and +/+ jejuni, but significantly decreased in -/- animals. Upon forskolin addition, net Na+ absorption decreased, Isc strongly increased, and net Cl- flux became secretory in Slc26a6-/- and +/+ jejuni. When luminal glucose was added to activate Na+/glucose cotransport, concomitant Cl+ absorption was significantly reduced in Slc26a6 -/- jejuni, while Na+ absorption increased to the same degree in Slc26a6 -/- and +/+ jejuni. Identical experiments in NHE3-deficient jejuni also showed reduced Na+ and Cl- absorption. Results further demonstrated that the lack of NHE3 rendered Na(+)and Cl- absorption unresponsive to inhibition by cAMP, but did not affect glucose-driven Na+ and Cl- absorption. Immunoblotting revealed comparable NHE3 abundance and distribution in apical membranes in Slc26a6-/- and +/+ mice. The data strongly suggests that Slc26a6 acts in concert with NHE3 in electroneutral salt absorption in the small intestine. Slc26a6 also serves to absorb Cl- during glucose-driven salt absorption.