Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units.
Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units.
复制标题
离体大鼠胆管上皮单位中 Cl(-) 依赖性分泌机制。
DOI：
10.1152/ajpgi.2001.281.2.g438
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Boyer,JL
中科院分区：
文献类型：
--
作者：
Singh,SK;Mennone,A;Gigliozzi,A;Fraioli,F;Boyer,JL
Cholangiocytes absorb and secrete fluid, modifying primary canalicular bile. In several Cl−-secreting epithelia, Na+-K+-2Cl−cotransport is a basolateral Cl−uptake pathway facilitating apical Cl−secretion. To determine if cholangiocytes possess similar mechanisms independent of CO2/HCO, we assessed Cl−-dependent secretion in rat liver isolated polarized bile duct units (IBDUs) by using videomicroscopy. Without CO2/HCO, forskolin (FSK) stimulated secretion entirely dependent on Na+and Cl−and inhibited by Na+-K+-2Cl−inhibitor bumetanide. Carbonic anhydrase inhibitor ethoxyzolamide had no effect on FSK-stimulated secretion, indicating negligible endogenous CO2/HCOtransport. In contrast, FSK-stimulated secretion was inhibited ∼85% by K+channel inhibitor Ba2+and blocked completely by bumetanide plus Ba2+. IBDU Na+-K+-2Cl−cotransport activity was assessed by recording intracellular pH during NH4Cl exposure. Bumetanide inhibited initial acidification rates due to NHentry in the presence and absence of CO2/HCO. In contrast, when stimulated by FSK, a 35% increase in Na+-K+-2Cl−cotransport activity occurred without CO2/HCO. These data suggest a cellular model of HCO-independent secretion in which Na+-K+-2Cl−cotransport maintains high intracellular Cl−concentration. Intracellular cAMP concentration increases activate basolateral K+conductance, raises apical Cl−permeability, and causes transcellular Cl−movement into the lumen. Polarized IBDU cholangiocytes are capable of vectorial Cl−-dependent fluid secretion independent of HCO. Bumetanide-sensitive Na+-K+-2Cl−cotransport, Cl−/HCOexchange, and Ba2+-sensitive K+channels are important components of stimulated fluid secretion in intrahepatic bile duct epithelium.
