Effects of Slc26a6 deletion and CFTR inhibition on HCO3- secretion by mouse pancreatic duct.
Pancreatic duct epithelium secretes HCO(3)(-)-rich fluid, which is dependent on cystic fibrosis transmembrane conductance regulator (CFTR). HCO(3)(-) transport across the apical membrane is thought to be mediated by both SLC26A6 Cl(-)-HCO(3)(-) exchange and CFTR HCO(3)(-) conductance. In this study we examined the relative contribution and interaction of SLC26A6 and CFTR in apical HCO(3)(-) transport. Interlobular pancreatic ducts were isolated from slc26a6 null mice. Intracellular pH (pH(i)) was measured by BCECF microfluorometry. Duct cells were stimulated with forskolin and alkalinized by acetate pre-pulse in the presence of HCO(3)(-)-CO(2). Apical HCO(3)(-) secretion was estimated from the recovery rate of pH(i) from alkaline load. When the lumen was perfused with high-Cl(-) solution, the rate of apical HCO(3)(-) secretion was increased by luminal application of CFTRinh-172 in ducts from wild-type mice but it was decreased in ducts from slc26a6 -/- mice. This suggests that slc26a6 and CFTR compensate/compete with each other for apical HCO(3)(-) secretion with high Cl(-) in the lumen. With high HCO(3)(-) in the lumen, luminal CFTRinh-172 reduced the rate of apical HCO(3)(-) secretion in both wild-type and slc26a6 -/- ducts. This suggests that HCO(3)(-) conductance of CFTR mediates a significant portion of apical HCO(3)(-) secretion with high HCO(3)(-) in the lumen.
Song
Ying
Y
Second Clinical College of Norman Bethune Medical Division, Jilin University, Changchun, China.
Ishiguro
Hiroshi
H
Yamamoto
Akiko
A
Jin
Chun Xiang
CX
Kondo
Takaharu
T
D000818:Animals; D017920:Antiporters / Q000235:genetics* / Q000502:physiology; D001639:Bicarbonates / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors* / Q000502:physiology; D017353:Gene Deletion; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018345:Mice, Knockout; D010183:Pancreatic Ducts / Q000378:metabolism*; D000076988:Sulfate Transporters
D017920:Antiporters; D001639:Bicarbonates; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator