Tuo Biguang, Riederer Brigitte, Wang Zhaohui, Colledge William H, Soleimani Manoocher, Seidler Ursula
Department of Gastroenterology and Hepatology, Hannover Medical School, Germany.
Gastroenterology. 2006 Feb;130(2):349-58. doi: 10.1053/j.gastro.2005.10.017.
BACKGROUND & AIMS: SLC26A6 is a recently identified apical Cl(-)/HCO(3)(-) exchanger with strong expression in murine duodenum. The present study was designed to examine the role of SLC26A6 in prostaglandin E(2) (PGE(2))-, forskolin-, and carbachol-induced duodenal HCO(3)(-) secretion.
Murine duodenal mucosal HCO(3)(-) secretion was examined in vitro in Ussing chambers and mucosal SLC26A6 expression levels were analyzed by semiquantitative reverse-transcription polymerase chain reaction.
Basal HCO(3)(-) secretion was diminished by 20%, PGE(2)-stimulated HCO(3)(-) secretory response by 59%, and carbachol-stimulated response was reduced by 35% in SLC26A6-/- compared with +/+ duodenal mucosa, whereas the forskolin-stimulated HCO(3)(-) secretory response was not different. In Cl(-)-free solutions, PGE(2)- and carbachol-stimulated HCO(3)(-) secretion was reduced by 81% and 44%, respectively, whereas forskolin-stimulated HCO(3)(-) secretion was not altered significantly. PGE(2) and carbachol, but not forskolin, were able to elicit a Cl(-)-dependent HCO(3)(-) secretory response in the absence of short-circuit current changes in cystic fibrosis transmembrane conductance regulator knockout mice.
In murine duodenum, PGE(2)-mediated HCO(3)(-) secretion is strongly SLC26A6 dependent and cystic fibrosis transmembrane conductance regulator independent, whereas forskolin-stimulated HCO(3)(-) secretion is completely SLC26A6 independent and cystic fibrosis transmembrane conductance regulator dependent. Carbachol-induced secretion is less pronounced, but occurs via both transport pathways. This suggests that PGE(2) and forskolin activate distinct HCO(3)(-) transport pathways in the murine duodenum.
SLC26A6是一种最近鉴定出的顶端Cl⁻/HCO₃⁻交换体，在小鼠十二指肠中高表达。本研究旨在探讨SLC26A6在前列腺素E₂（PGE₂）、福斯可林和卡巴胆碱诱导的十二指肠HCO₃⁻分泌中的作用。
在Ussing室中体外检测小鼠十二指肠黏膜HCO₃⁻分泌，并通过半定量逆转录聚合酶链反应分析黏膜SLC26A6表达水平。
与野生型十二指肠黏膜相比，SLC26A6基因敲除小鼠的基础HCO₃⁻分泌减少20%，PGE₂刺激的HCO₃⁻分泌反应减少59%，卡巴胆碱刺激的反应减少35%，而福斯可林刺激的HCO₃⁻分泌反应无差异。在无Cl⁻溶液中，PGE₂和卡巴胆碱刺激的HCO₃⁻分泌分别减少81%和44%，而福斯可林刺激的HCO₃⁻分泌无明显改变。在囊性纤维化跨膜传导调节因子基因敲除小鼠中，PGE₂和卡巴胆碱能在无短路电流变化的情况下引发Cl⁻依赖性HCO₃⁻分泌反应，但福斯可林不能。
在小鼠十二指肠中，PGE₂介导的HCO₃⁻分泌强烈依赖SLC26A6且不依赖囊性纤维化跨膜传导调节因子，而福斯可林刺激的HCO₃⁻分泌完全不依赖SLC26A6且依赖囊性纤维化跨膜传导调节因子。卡巴胆碱诱导的分泌不太明显，但通过两种转运途径发生。这表明PGE₂和福斯可林在小鼠十二指肠中激活不同的HCO₃⁻转运途径。
