The electroneutral Na+:HCO3- cotransporter NBCn1 is a major pHi regulator in murine duodenum
The electroneutral Na+:HCO3- cotransporter NBCn1 is a major pHi regulator in murine duodenum
复制标题
DOI：
10.1113/jphysiol.2011.226506
复制
发表时间：
2012-07-01
影响因子：
5.5
通讯作者：
Seidler, Ursula
中科院分区：
文献类型：
--
作者：
Chen, Mingmin;Praetorius, Jeppe;Seidler, Ursula
十二指肠细胞pH(i)的控制和HCO3-的分泌保护近端十二指肠免受胃酸的损伤。十二指肠细胞pH控制的分子细节尚不清楚。据报道，电中性Na+:HCO3-共转运体NBCn1 （Slc4a7）在十二指肠选择性表达（在上消化道内）。我们的目的是确定NBCn1和NBCe2在十二指肠细胞内pH调节以及基础和激动剂刺激的十二指肠碳酸氢盐分泌(J（HCO3)(-)）中的作用，利用遗传slc4a7和slc4a5破坏的小鼠模型。在体内用slc4a7（-/-）、slc4a7（+/+）、slc4a5（-/-）、slc4a5（+/+）小鼠十二指肠单次灌注，在离体十二指肠粘膜用pH-stat滴定法测定基础和福斯可林（FSK）刺激的J(HCO3)（-）。在酸化完整绒毛和分离十二指肠细胞后，用荧光法评估十二指肠细胞HCO3-摄取率。Slc4a7（-/-）小鼠的十二指肠HCO3-分泌明显低于Slc4a7（+/+）小鼠。在slc4a7（-/-）离体十二指肠粘膜中，fsk刺激的HCO3-分泌显著减少。在完整绒毛中测量时，slc4a7（-/-）与slc4a7（+/+）绒毛十二指肠细胞相比，Na+-和HCO3-依赖的碱基摄取率显著降低。碳酸酐酶（CA）介导的CO2水合作用在slc4a7（+/+）十二指肠基础或fsk刺激的分泌中没有明显的HCO3-供应机制，但在slc4a7（-/-）十二指肠中是一种重要的替代HCO3-供应机制。NBCe2 （Slc4a5）十二指肠mRNA表达水平明显降低，其破坏不影响十二指肠HCO3-分泌。电中性的Na+:HCO3-共转运体NBCn1 （slc4a7）是一个主要的十二指肠HCO3-进口商，在基础和fsk刺激的HCO3-分泌过程中提供HCO3-。
Duodenocyte pH(i) control and HCO3- secretion protects the proximal duodenum against damage by gastric acid. The molecular details of duodenocyte pH control are not well understood. A selective duodenal expression (within the upper GI tract) has been reported for the electroneutral Na+:HCO3- cotransporter NBCn1 (Slc4a7). We aimed to determine the role of NBCn1 and NBCe2 in duodenocyte intracellular pH regulation as well as basal and agonist-stimulated duodenal bicarbonate secretion (J(HCO3)(-)), exploiting mouse models of genetic slc4a7 and slc4a5 disruption. Basal and forskolin (FSK)-stimulated J(HCO3)(-) was measured by single-pass perfusion in the duodenum of slc4a7(-/-) and slc4a7(+/+) as well as slc4a5(-/-) and slc4a5(+/+) mice in vivo, and by pH-stat titration in isolated duodenal mucosa in vitro. Duodenocyte HCO3- uptake rates were fluorometrically assessed after acidification of intact villi and of isolated duodenocytes. Slc4a7(-/-) mice displayed significantly lower basal and FSK-stimulated duodenal HCO3- secretion than slc4a7(+/+) littermates in vivo. FSK-stimulated HCO3- secretion was significantly reduced in slc4a7(-/-) isolated duodenal mucosa. Na+- and HCO3--dependent base uptake rates were significantly decreased in slc4a7(-/-) compared with slc4a7(+/+) villus duodenocytes when measured in intact villi. Carbonic anhydrase (CA)-mediated CO2 hydration played no apparent role as a HCO3- supply mechanism for basal or FSK-stimulated secretion in the slc4a7(+/+) duodenum, but was an important alternative HCO3- supply mechanism in the slc4a7(-/-) duodenum. NBCe2 (Slc4a5) displayed markedly lower duodenal mRNA expression levels, and its disruption did not interfere with duodenal HCO3- secretion. The electroneutral Na+:HCO3- cotransporter NBCn1 (slc4a7) is a major duodenal HCO3- importer that supplies HCO3- during basal and FSK-stimulated HCO3- secretion.