PANCREATIC DUCT CELL PHYSIOLOGY

Electrophysiological studies have determined the fundamental mechanism s underlying fluid and electrolyte transport by the pancreatic duct ce ll. Stimulated fluid and bicarbonate secretion by these cells involves activation of an apical membrane chloride channel, the cystic fibrosi s transmembrane conductance regulator (CFTR). The intracellular proton s that accumulate during this process are extruded basolaterally, poss ibly by proton pumps inserted into the plasma membrane. Although secre tion is clearly regulated by secretin and the cyclic AMP pathway, it i s apparent that other agents (acetylcholine, bombesin, and substance P ), acting through calcium and other pathways, can also regulate the pr ocess. With the exception of CFTR, however, the sites of regulation ha ve not been completely established. As a target of both protein kinase A and protein kinase C, CFTR is one potential site for regulation by different signaling pathways. Furthermore, CFTR may have intracellular functions, raising the possibility that its activation affects additi onal duct cell processes.