Molecular Mechanism of Pancreatic Bicarbonate Secretion

ABSTRACT

Thanks to recent progress in availability of molecular and functional techniques it became possible to search for the basic molecular and cellular processes that mediate and control HCO3- and fluid secretion by the pancreatic duct. The coordinated action of various transporters on the luminal and basolateral membranes of polarized epithelial cells mediates the transepithelial HCO3- transport, which involves HCO3- absorption in the resting state and HCO3- secretion in the stimulated state. The overall process of HCO3- secretion can be divided into two steps. First, HCO3- in the blood enters the ductal epithelial cells across the basolateral membrane either by simple diffusion in the forms of CO2 and H2O or by the action of an Na+-coupled transporter, a Na+-HCO3- cotranporter (NBC) identified as pNBC1. Subsequently, the cells secrete HCO3- to the luminal space using at least two HCO3- exit mechanisms at the luminal membrane. One of the critical transporters needed for all forms of HCO3- secretion across the luminal membrane is the cystic fibrosis transmembrane conductance regulator (CFTR). In the resting state the pancreatic duct, and probably other HCO3- secretory epithelia, absorb HCO3-. Interestingly, CFTR also control this mechanism. In this review, we discuss recent progress in understanding epithelial HCO3- transport, in particular the nature of the luminal transporters and their regulation by CFTR.