Stimulation of HCO3– Secretion across Cystic Fibrosis Pancreatic Duct Cells by Extracellular ATP

Previous studies have demonstrated that extracellular ATP is able to activate Ca2+-dependent Cl– channels which may be important in circumventing the defective cAMP-dependent pancreatic ductal HCO3– secretion in cystic fibrosis (CF). The present study further investigated the effect of extracellular ATP on the stimulation of HCO3– secretion across CF pancreatic duct cells (CFPAC-1). Cells were grown in culture plate inserts which enabled the access of a pH microelectrode to the apical compartment. Changes in apical pH upon stimulation by extracellular ATP, as an indication of HCO3– secretion, were measured. ATP induced a rapid increase in apical pH, which reached a plateau with an averaged pH unit of 0.3 higher than that measured in unstimulated cells. The effect of ATP was concentration dependent. The ATP-induced change in pH could be blocked by apical addition of Cl– channel blockers, indicating that activation of apical Cl– channel is vital for HCO3– secretion by the pancreatic duct cells. Together with the previous finding, the present study suggests that HCO3– secretion may be stimulated in CF pancreatic duct cells by extracellular ATP via a cAMP-independent pathway.