Molecular and cellular regulation of pancreatic duct cell function

PURPOSE OF REVIEW: The pancreatic duct epithelium is remarkable for its capacity to secrete HCO3 ions at concentrations as high as 140 mmol/l. The properties of the key transporters involved in this process and the central role played by cystic fibrosis transmembrane conductance regulator (CFTR) are the main focus of this review. RECENT FINDINGS: The Cl/HCO3 exchanger at the apical membrane of pancreatic duct cells is now known to be SLC26A6. The 1: 2 stoichiometry and electrogenicity of this exchanger enable it to contribute to the secretion of HCO3 at high concentrations. The apical CFTR channels also appear to have sufficient HCO3 permeability to contribute directly to HCO3 secretion. There is a strong possibility that the Ca-activated Cl channels at the apical membrane are members of the bestrophin family which, like CFTR, are also permeable to HCO3. More has been learned about the complex interactions between CFTR and other transporters within macromolecular complexes coordinated at the apical membrane by scaffolding proteins. Further details are also emerging of the protective paracrine roles of nucleotides, nucleosides, bile acids and trypsin in the regulation of ductal secretion. SUMMARY: Most of the key transporters involved in Cl and HCO3 secretion have now been identified and characterized. Current research focuses on the molecular interactions between these transporters and the ways in which they are regulated by extracellular signals. © 2009 Lippincott Williams & Wilkins, Inc.