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.
Cheung
C Y
CY
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
Wang
X F
XF
Chan
H C
HC
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D003550:Cystic Fibrosis / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D010183:Pancreatic Ducts / Q000187:drug effects* / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D001639:Bicarbonates; D018118:Chloride Channels; D062367:ortho-Aminobenzoates; D000255:Adenosine Triphosphate; C001209:fenamic acid