Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct
Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct
复制标题
DOI：
10.1152/ajpgi.00286.2006
复制
发表时间：
2007-01-01
影响因子：
4.5
通讯作者：
Soleimani, Manoocher
中科院分区：
文献类型：
--
作者：
Ishiguro, Hiroshi;Namkung, Wan;Soleimani, Manoocher
使用Slc 26 a6缺失和野生型（WT）小鼠研究Slc 26 a6（PAT 1）对胰管细胞中顶端Cl-/HCO 3-交换和碳酸氢盐分泌的作用。用pH敏感染料BCECF在微灌注的小叶间导管中测量顶端Cl-/HCO 3-交换活性。根尖[Cl-]（i）/[HCO_3-]（o）交换的HCO_3-内流模式（其中括号表示浓度，下标i和o分别表示细胞内和细胞外）在Slc 26 a6缺失小鼠中显著上调（P < 0.01 vs. WT），而在Slc 26 a6敲除小鼠中，顶端[Cl-]（o）/[HCO 3-]（i）交换的HCO 3-流出模式减少（P < 0.05相对于WT），表明Slc 26 a6介导的HCO 3-转运的单向性。WT和Slc 26 a6基因敲除小鼠的小叶间导管液体分泌率相似（P > 0.05）。此外，当在基础和促分泌素刺激条件下从整个动物收集胰液时，无论是汁液体积还是其pH都没有显示WT和Slc 26 a6缺失小鼠之间的差异。半定量RT-PCR显示Slc 26 a6敲除胰腺中Slc 26 a3（E3）表达上调超过5倍。总之，这些结果表明Slc 26 a6在顶膜HCO 3流出中的作用，并且还表明存在稳健的Slc 26 a3补偿性上调，其可以取代Slc 26 a6在胰管中的功能。
The role of Slc26a6 (PAT1) on apical Cl-/HCO3- exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT) mice. Apical Cl-/HCO3- exchange activity was measured with the pH-sensitive dye BCECF in microperfused interlobular ducts. The HCO3--influx mode of apical [Cl-](i)/[HCO3-](o) exchange (where brackets denote concentration and subscripts i and o denote intra- and extracellular, respectively) was dramatically upregulated in Slc26a6 null mice (P < 0.01 vs. WT), whereas the HCO3--efflux mode of apical [Cl-](o)/[HCO3-](i) exchange was decreased in Slc26a6 null mice (P < 0.05 vs. WT), suggesting the unidirectionality of the Slc26a6-mediated HCO3- transport. Fluid secretory rate in interlobular ducts were comparable in WT and Slc26a6 null mice (P > 0.05). In addition, when pancreatic juice was collected from whole animal in basal and secretin-stimulated conditions, neither juice volume nor its pH showed differences between WT and Slc26a6 null mice. Semi-quantitative RT-PCR demonstrated more than fivefold upregulation in Slc26a3 (DRA) expression in Slc26a6 knockout pancreas. In conclusion, these results point to the role of Slc26a6 in HCO3--efflux at the apical membrane and also suggest the presence of a robust Slc26a3 compensatory upregulation, which can replace the function of Slc26a6 in pancreatic ducts.