Ca2+ activates cystic fibrosis transmembrane conductance regulator- and Cl- -dependent HCO3 transport in pancreatic duct cells.

摘要: Abstract Pancreatic duct cells secrete bicarbonate-rich fluids, which are important for maintaining the patency of pancreatic ductal trees as well intestinal digestive function. The bulk bicarbonate secretion in luminal membrane is mediated by a Cl−-dependent mechanism (Cl−/HCO exchange), and we previously reported that CFTR-dependent cAMP-activated (Lee, M. G., Choi, J. Y., Luo, X., Strickland, E., Thomas, P. J., Muallem, S. (1999)J. Biol. Chem. 274, 14670–14677). In present study, provide comprehensive evidence calcium signaling also activates same CFTR- HCO transport. ATP trypsin evoked intracellular duct-derived through activation purinergic protease-activated receptors, respectively. Cl−/HCO exchange activity was measured recording pHi response to [Cl−]o changes perfusate. perfusate containing high concentrations K+, blocks Cl− movement electrogenic or K+-coupled pathways, highly stimulated CAPAN-1 expressing wild-type CFTR, but not CFPAC-1 have defective (ΔF508) CFTR. Notably, adenoviral transfection CFTR completely restored stimulatory effect on exchange. addition, chelation 1,2-bis(2-aminophenoxy)ethane-N,N,N,N′-tetraacetic acid (BAPTA) treatment abolished agonists These results molecular basis calcium-induced highlight importance epithelial induced various stimuli.