Changes in cell volume in pancreatic duct cells. Effect of secretagogues and CFTR expression

Previous results from our group have demonstrated that, in CFTR-transfected murine C127 cells incubated under Cl--free conditions, "isotonic" shrinkage is more rapid in CFTRw/t than in CFTRΔF508 cells, a difference overcome in the latter model by the addition of exogenous ATP. Moreover, compared with ΔF508 cells, isotonic cell shrinkage of CFTRw/t -expressing cells is associated with a significantly higher ATP extrusion (Rotoli et al., Biochem. Biophys. Res. Commun. 227, 755-761 1996). In the present report changes in cell volume and ion content occurring during secretory processes are evaluated in pancreatic duct cells. The models employed were pancreatic carcinoma cells which express normal (CAPAN-1 line) or ΔF508 (CFPAC-1 line) CFTR. Under isotonic conditions, in CFTR-expressing CAPAN-1 cells secretin or 8-Br-cAMP/ teophilline mixture cause a 30% cell shrinkage associated to significant losses of sodium, chloride, and bicarbonate, as demonstrated by significant changes in cytoplasmic pH. These changes are not observed in ΔF508CFTR CFPAC-1 cells but are mimicked by ATP treatment. As in C127 cells, also in pancreatic duct cells Cl--free incubation triggers isotonic shrinkage and ATP extrusion which is greater in CAPAN-1 than in CFPAC-1 cells. These results suggest that ATP may be involved in the modifications of ion channel activities which occur during secretion in pancreatic duct cells.