Molecular Mechanism of Pancreatic Bicarbonate Secretion

Molecular Mechanism of Pancreatic Bicarbonate Secretion

<P> 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 HCO<SUB>3</SUB><SUP>&#8291;</SUP> 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 HCO<SUB>3</SUB><SUP>&#8291;</SUP> transport, which involves HCO<SUB>3</SUB><SUP>&#8291;</SUP> absorption in the resting state and HCO<SUB>3</SUB><SUP>&#8291;</SUP> secretion in the stimulated state. The overall process of HCO<SUB>3</SUB><SUP>&#8291;</SUP> secretion can be divided into two steps. First, HCO<SUB>3</SUB><SUP>&#8291;</SUP> in the blood enters the ductal epithelial cells across the basolateral membrane either by simple diffusion in the forms of CO<SUB>2</SUB> and H<SUB>2</SUB>O or by the action of an Na<SUP>&#8290;</SUP>-coupled transporter, a Na<SUP>&#8290;</SUP>-HCO<SUB>3</SUB><SUP>&#8291;</SUP> cotranporter (NBC) identified as pNBC1. Subsequently, the cells secrete HCO<SUB>3</SUB><SUP>&#8291;</SUP> to the luminal space using at least two HCO<SUB>3</SUB><SUP>&#8291;</SUP> exit mechanisms at the luminal membrane. One of the critical transporters needed for all forms of HCO<SUB>3</SUB><SUP>&#8291;</SUP> secretion across the luminal membrane is the cystic fibrosis transmembrane conductance regulator (CFTR). In the resting state the pancreatic duct, and probably other HCO<SUB>3</SUB><SUP>&#8291;</SUP> secretory epithelia, absorb HCO<SUB>3</SUB><SUP>&#8291;</SUP>. Interestingly, CFTR also control this mechanism. In this review, we discuss recent progress in understanding epithelial HCO<SUB>3</SUB><SUP>&#8291;</SUP> transport, in particular the nature of the luminal transporters and their regulation by CFTR.